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Sample records for pre-erythrocytic stage infection

  1. Pre-erythrocytic-stage immune effector mechanisms in Plasmodium spp. infections.

    PubMed Central

    Doolan, D L; Hoffman, S L

    1997-01-01

    The potent protective immunity against malaria induced by immunization of mice and humans with radiation-attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T-cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo. By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide-adjuvant vaccines, we have demonstrated that different T-cell-dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre-erythrocytic-stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity. PMID:9355128

  2. 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. PMID:25200253

  3. IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection

    PubMed Central

    Jagannathan, Prasanna; Nankya, Felistas; Stoyanov, Cristina; Eccles-James, Ijeoma; Sikyomu, Esther; Naluwu, Kate; Wamala, Samuel; Nalubega, Mayimuna; Briggs, Jessica; Bowen, Katherine; Bigira, Victor; Kapisi, James; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.

    2015-01-01

    Background. The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens. Methods. We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity. Results. IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009). Conclusions. In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria. PMID:25520427

  4. 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

  5. Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development

    PubMed Central

    Aguiar, Joao C.; Bolton, Jessica; Wanga, Joyce; Sacci, John B.; Iriko, Hideyuki; Mazeika, Julie K.; Han, Eun-Taek; Limbach, Keith; Patterson, Noelle B.; Sedegah, Martha; Cruz, Ann-Marie; Tsuboi, Takafumi; Hoffman, Stephen L.; Carucci, Daniel; Hollingdale, Michael R.; Villasante, Eileen D.; Richie, Thomas L.

    2015-01-01

    Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Methodology Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. Conclusions These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. Trial Registration ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015 PMID:26292257

  6. 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. PMID:26469724

  7. Complex Minigene Library Vaccination for Discovery of Pre-Erythrocytic Plasmodium T Cell Antigens

    PubMed Central

    Stone, Brad C.; Kas, Arnold; Billman, Zachary P.; Fuller, Deborah H.; Fuller, James T.; Shendure, Jay; Murphy, Sean C.

    2016-01-01

    Development of a subunit vaccine targeting liver-stage Plasmodium parasites requires the identification of antigens capable of inducing protective T cell responses. However, traditional methods of antigen identification are incapable of evaluating T cell responses against large numbers of proteins expressed by these parasites. This bottleneck has limited development of subunit vaccines against Plasmodium and other complex intracellular pathogens. To address this bottleneck, we are developing a synthetic minigene technology for multi-antigen DNA vaccines. In an initial test of this approach, pools of long (150 bp) antigen-encoding oligonucleotides were synthesized and recombined into vectors by ligation-independent cloning to produce two DNA minigene library vaccines. Each vaccine encoded peptides derived from 36 (vaccine 1) and 53 (vaccine 2) secreted or transmembrane pre-erythrocytic P. yoelii proteins. BALB/cj mice were vaccinated three times with a single vaccine by biolistic particle delivery (gene gun) and screened for interferon-γ-producing T cell responses by ELISPOT. Library vaccination induced responses against four novel antigens. Naïve mice exposed to radiation-attenuated sporozoites mounted a response against only one of the four novel targets (PyMDH, malate dehydrogenase). The response to PyMDH could not be recalled by additional homologous sporozoite immunizations but could be partially recalled by heterologous cross-species sporozoite exposure. Vaccination against the dominant PyMDH epitope by DNA priming and recombinant Listeria boosting did not protect against sporozoite challenge. Improvements in library design and delivery, combined with methods promoting an increase in screening sensitivity, may enable complex minigene screening to serve as a high-throughput system for discovery of novel T cell antigens. PMID:27070430

  8. Complex Minigene Library Vaccination for Discovery of Pre-Erythrocytic Plasmodium T Cell Antigens.

    PubMed

    Stone, Brad C; Kas, Arnold; Billman, Zachary P; Fuller, Deborah H; Fuller, James T; Shendure, Jay; Murphy, Sean C

    2016-01-01

    Development of a subunit vaccine targeting liver-stage Plasmodium parasites requires the identification of antigens capable of inducing protective T cell responses. However, traditional methods of antigen identification are incapable of evaluating T cell responses against large numbers of proteins expressed by these parasites. This bottleneck has limited development of subunit vaccines against Plasmodium and other complex intracellular pathogens. To address this bottleneck, we are developing a synthetic minigene technology for multi-antigen DNA vaccines. In an initial test of this approach, pools of long (150 bp) antigen-encoding oligonucleotides were synthesized and recombined into vectors by ligation-independent cloning to produce two DNA minigene library vaccines. Each vaccine encoded peptides derived from 36 (vaccine 1) and 53 (vaccine 2) secreted or transmembrane pre-erythrocytic P. yoelii proteins. BALB/cj mice were vaccinated three times with a single vaccine by biolistic particle delivery (gene gun) and screened for interferon-γ-producing T cell responses by ELISPOT. Library vaccination induced responses against four novel antigens. Naïve mice exposed to radiation-attenuated sporozoites mounted a response against only one of the four novel targets (PyMDH, malate dehydrogenase). The response to PyMDH could not be recalled by additional homologous sporozoite immunizations but could be partially recalled by heterologous cross-species sporozoite exposure. Vaccination against the dominant PyMDH epitope by DNA priming and recombinant Listeria boosting did not protect against sporozoite challenge. Improvements in library design and delivery, combined with methods promoting an increase in screening sensitivity, may enable complex minigene screening to serve as a high-throughput system for discovery of novel T cell antigens. PMID:27070430

  9. Modeling Combinations of Pre-erythrocytic Plasmodium falciparum Malaria Vaccines.

    PubMed

    Walker, Andrew S; Lourenço, José; Hill, Adrian V S; Gupta, Sunetra

    2015-12-01

    Despite substantial progress in the control of Plasmodium falciparum infection due to the widespread deployment of insecticide-treated bed nets and artemisinin combination therapies, malaria remains a prolific killer, with over half a million deaths estimated to have occurred in 2013 alone. Recent evidence of the development of resistance to treatments in both parasites and their mosquito vectors has underscored the need for a vaccine. Here, we use a mathematical model of the within-host dynamics of P. falciparum infection, fit to data from controlled human malaria infection clinical trials, to predict the efficacy of co-administering the two most promising subunit vaccines, RTS,S/AS01 and ChAd63-MVA ME-TRAP. We conclude that currently available technologies could be combined to induce very high levels of sterile efficacy, even in immune-naive individuals. PMID:26503278

  10. 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

  11. Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

    PubMed

    Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

    2016-03-01

    The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes. PMID:26610026

  12. Modeling the three stages in HIV infection.

    PubMed

    Hernandez-Vargas, Esteban A; Middleton, Richard H

    2013-03-01

    A typical HIV infection response consists of three stages: an initial acute infection, a long asymptomatic period and a final increase in viral load with simultaneous collapse in healthy CD4+T cell counts. The majority of existing mathematical models give a good representation of either the first two stages or the last stage of the infection. Using macrophages as a long-term active reservoir, a deterministic model is proposed to explain the three stages of the infection including the progression to AIDS. Simulation results illustrate how chronic infected macrophages can explain the progression to AIDS provoking viral explosion. Further simulation studies suggest that the proposed model retains its key properties even under moderately large parameter variations. This model provides important insights on how macrophages might play a crucial role in the long term behavior of HIV infection. PMID:23238280

  13. Mechanisms of Stage-Transcending Protection Following Immunization of Mice with Late Liver Stage-Arresting Genetically Attenuated Malaria Parasites

    PubMed Central

    Sack, Brandon K.; Keitany, Gladys J.; Vaughan, Ashley M.; Miller, Jessica L.; Wang, Ruobing; Kappe, Stefan H. I.

    2015-01-01

    Malaria, caused by Plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. Development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. Historically, malaria vaccine development efforts have targeted each stage in isolation. An ideal vaccine, however, would target multiple life cycle stages with multiple arms of the immune system and be capable of eliminating initial infection in the liver, the subsequent blood stage infection, and would prevent further parasite transmission. We have previously shown that immunization of mice with Plasmodium yoelii genetically attenuated parasites (GAP) that arrest late in liver stage development elicits stage-transcending protection against both a sporozoite challenge and a direct blood stage challenge. Here, we show that this immunization strategy engenders both T- and B-cell responses that are essential for stage-transcending protection, but the relative importance of each is determined by the host genetic background. Furthermore, potent anti-blood stage antibodies elicited after GAP immunization rely heavily on FC-mediated functions including complement fixation and FC receptor binding. These protective antibodies recognize the merozoite surface but do not appear to recognize the immunodominant merozoite surface protein-1. The antigen(s) targeted by stage-transcending immunity are present in both the late liver stages and blood stage parasites. The data clearly show that GAP-engendered protective immune responses can target shared antigens of pre-erythrocytic and erythrocytic parasite life cycle stages. As such, this model constitutes a powerful tool to identify novel, protective and stage-transcending T and B cell targets for incorporation into a multi-stage subunit vaccine. PMID:25974076

  14. 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

  15. 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

  16. 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

  17. 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. PMID:26760062

  18. Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates

    PubMed Central

    Longley, Rhea J.; Salman, Ahmed M.; Cottingham, Matthew G.; Ewer, Katie; Janse, Chris J.; Khan, Shahid M.; Spencer, Alexandra J.; Hill, Adrian V. S.

    2015-01-01

    The development of an efficacious Plasmodium falciparum malaria vaccine remains a top priority for global health. Vaccination with irradiated sporozoites is able to provide complete sterile protection through the action of CD8+ T cells at the liver-stage of infection. However, this method is currently unsuitable for large-scale deployment and focus has instead turned to the development of sub-unit vaccines. Sub-unit vaccine efforts have traditionally focused on two well-known pre-erythrocytic antigens, CSP and TRAP, yet thousands of genes are expressed in the liver-stage. We sought to assess the ability of eight alternative P. falciparum pre-erythrocytic antigens to induce a high proportion of CD8+ T cells. We show that all antigens, when expressed individually in the non-replicating viral vectors ChAd63 and MVA, are capable of inducing an immune response in mice. Furthermore, we also developed chimeric P. berghei parasites expressing the cognate P. falciparum antigen to enable assessment of efficacy in mice. Our preliminary results indicate that vectors encoding either PfLSA1 or PfLSAP2 are capable of inducing sterile protection dependent on the presence of CD8+ T cells. This work has identified two promising P. falciparum liver-stage candidate antigens that will now undergo further testing in humans. PMID:26139288

  19. Bioluminescence Imaging to Detect Late Stage Infection of African Trypanosomiasis.

    PubMed

    Burrell-Saward, Hollie; Ward, Theresa H

    2016-01-01

    Human African trypanosomiasis (HAT) is a multi-stage disease that manifests in two stages; an early blood stage and a late stage when the parasite invades the central nervous system (CNS). In vivo study of the late stage has been limited as traditional methodologies require the removal of the brain to determine the presence of the parasites. Bioluminescence imaging is a non-invasive, highly sensitive form of optical imaging that enables the visualization of a luciferase-transfected pathogen in real-time. By using a transfected trypanosome strain that has the ability to produce late stage disease in mice we are able to study the kinetics of a CNS infection in a single animal throughout the course of infection, as well as observe the movement and dissemination of a systemic infection. Here we describe a robust protocol to study CNS infections using a bioluminescence model of African trypanosomiasis, providing real time non-invasive observations which can be further analyzed with optional downstream approaches. PMID:27284970

  20. Two-Stage Procedure for Infected Aortic Graft Pseudoaneurysm

    PubMed Central

    von Aspern, Konstantin; Etz, Christian D.; Mohr, Friedrich W.; Battellini, Roberto R.

    2015-01-01

    Prosthetic graft infections with mediastinitis following aortic surgery are rare, yet represent grave complications yielding high morbidity and mortality. We present the case of a 57-year-old female patient with past history of emergent surgery for iatrogenic Type A dissection treated by supracoronary ascending aortic replacement. Four months after the initial surgery, a sternal fistula had formed and due to severe bleeding emergent reoperation was required. Imaging and pathology on admission revealed an infected pseudoaneurysm at the distal aortic prosthesis and mediastinitis with methicillin-resistant Staphylococcus aureus. Rescue surgery was performed by means of a two-stage approach, with extensive debridement, graft replacement and continuous antiseptic lavage in a first step and an omental wrapping of the new prosthesis in a second stage 24 hours later. During 10 years of follow-up, no recurrent infection occurred. The operative approach and general considerations for management of infected pseudoaneurysms are discussed. PMID:27069945

  1. Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model.

    PubMed

    Sahu, Tejram; Lambert, Lynn; Herrod, Jessica; Conteh, Solomon; Orr-Gonzalez, Sachy; Carter, Dariyen; Duffy, Patrick E

    2015-01-01

    Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites (SPZ) under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to SPZ and T-cell responses to liver stage (LS) parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on LS parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb LS development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine, a drug that kills LS parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates LS parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. PMID:25914686

  2. Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model

    PubMed Central

    Sahu, Tejram; Lambert, Lynn; Herrod, Jessica; Conteh, Solomon; Orr-Gonzalez, Sachy; Carter, Dariyen; Duffy, Patrick E.

    2015-01-01

    Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites (SPZ) under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to SPZ and T-cell responses to liver stage (LS) parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on LS parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb LS development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine, a drug that kills LS parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates LS parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. PMID:25914686

  3. 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. PMID:25149354

  4. Genes expressed in Brugia malayi infective third stage larvae.

    PubMed

    Blaxter, M L; Raghavan, N; Ghosh, I; Guiliano, D; Lu, W; Williams, S A; Slatko, B; Scott, A L

    1996-04-01

    We have used a tag sequencing approach to survey genes expressed in the third stage infective larvae of the human filarial nematode parasite Brugia malayi. RNA was isolated from late vector-stage L3 larvae after days 9 or 10 of infection in mosquitos, and converted to cDNA by reverse transcriptase. Double-stranded cDNA was produced by either conventional methods (non-SL cDNA library) or by PCR using the nematode spliced leader (SLI) and oligo(dT) primers (SL cDNA library). Two clone libraries (one from SL and one from non-SL cDNAs) were constructed in lambda ZapII. A set of these full-length clones was selected and 596 inserts were sequenced from the 5' end. We have identified 364 B. malayi genes (the majority of which are new) that encode housekeeping proteins, structural proteins, proteins of immediate immunological or drug-discovery interest as well as a large class of novel sequences which may prove to have significant involvement in host invasion. Extensive, genome-wide approaches to the analysis of larval gene expression are now possible for B. malayi. We present several examples of this approach. PMID:8784774

  5. 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. PMID:27226891

  6. 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

  7. Stage-dependent model for Hantavirus infection: the effect of the initial infection-free period.

    PubMed

    Reinoso, José A; de la Rubia, F Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s. PMID:23679449

  8. Stage-dependent model for Hantavirus infection: The effect of the initial infection-free period

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s.

  9. The Malarial Serine Protease SUB1 Plays an Essential Role in Parasite Liver Stage Development

    PubMed Central

    Suarez, Catherine; Volkmann, Katrin; Gomes, Ana Rita; Billker, Oliver; Blackman, Michael J.

    2013-01-01

    Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. Whilst elements of liver stage merozoite biology are similar to those in the much better-studied blood stage merozoites, little is known of the molecular players involved in liver stage merozoite production. To facilitate the study of liver stage biology we developed a strategy for the rapid production of complex conditional alleles by recombinase mediated engineering in Escherichia coli, which we used in combination with existing Plasmodium berghei deleter lines expressing Flp recombinase to study subtilisin-like protease 1 (SUB1), a conserved Plasmodium serine protease previously implicated in blood stage merozoite maturation and egress. We demonstrate that SUB1 is not required for the early stages of intrahepatic growth, but is essential for complete development of the liver stage schizont and for production of hepatic merozoites. Our results indicate that inhibitors of SUB1 could be used in prophylactic approaches to control or block the clinically silent pre-erythrocytic stage of the malaria parasite life cycle. PMID:24348254

  10. Characterization of Liver CD8 T Cell Subsets that are Associated with Protection Against Pre-erythrocytic Plasmodium Parasites.

    PubMed

    Zarling, Stasya; Krzych, Urszula

    2015-01-01

    Murine models of malaria, such as Plasmodium berghei (Pb) and Plasmodium yoelii (Py), have been used for decades to identify correlates of protection associated with immunization using radiation-attenuated sporozoites (RAS). To date, RAS is the only known immunization regimen to consistently deliver 100 % sterilizing immunity and is considered the "gold standard" of protection against malaria. The ability to isolate lymphocytes directly from the liver of immune mice has facilitated the identification of correlates of protection at the site of infection. Liver CD8 T cells have been identified as a key factor in mediating protection against challenge with infectious Plasmodium sporozoites. Liver CD3 + CD8 T cells can further be divided into subsets based on the expression of specific surface molecules and the increase of CD8 effector memory (TEM) cells (identified by the phenotype CD44(+)CD62L(-)) has been shown to mediate protection by releasing of IFN-γ while CD8 central memory (TCM) cells (CD44(+)CD62L(+)) are important for maintaining long-term protection.Identification of multiple CD8 T cell subsets present in the liver relies on the ability to detect multiple surface markers simultaneously. Polychromatic flow cytometry affords the user with the ability to distinguish multiple lymphocyte populations as well as subsets defined within each population. In this chapter we present a basic 9-color surface staining panel that can be used to identify CD8 TEM, CD8 TCM, short-lived effector cells (SLECs), and memory precursor cells (MPECs) as well as identify those cells which have recently undergone degranulation (surface expression of CD107a). This panel has been designed to allow for the addition of intracellular staining for IFN-γ on other available channels (such as PE) as is discussed in another chapter for analysis of functional CD8 T cell responses. PMID:26450377

  11. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    PubMed Central

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  12. Prevalence of psychiatric disorders in early stages of HIV infection.

    PubMed

    Brown, G R; Rundell, J R; McManis, S E; Kendall, S N; Zachary, R; Temoshok, L

    1992-01-01

    As part of a military universal HIV screening program, 442 men were assessed for the presence of DSM-III-R defined psychiatric disorders and symptoms of anxiety and depression after notification of HIV seroconversion. Of them, 84.4% were in the earliest, asymptomatic stages of disease at the time of interview (96% did not have AIDS). The Structured Clinical Interview for DSM-III-R and Structured Interview Guide for the Hamilton Anxiety and Depression Scales were used. Relevant comparisons were made to Epidemiologic Catchment Area prevalence data. HIV seropositive men were more likely than age-matched men in the community to have current diagnoses of major depression (ages 18-44) and anxiety disorders (ages 25-44). Higher lifetime rates of major depression and alcohol use disorder, and high current prevalence of sexual dysfunction (21.7%) were noted. We conclude that men who become HIV seropositive have high rates of mood and substance use disorders prior to knowledge of seroconversion, and that early in the course of HIV infection men are at risk for developing major depression, anxiety disorders, and disorders of sexual desire. PMID:1438661

  13. Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection

    PubMed Central

    Ananworanich, Jintanat; Sacdalan, Carlo P.; Pinyakorn, Suteeraporn; Chomont, Nicolas; de Souza, Mark; Luekasemsuk, Tassanee; Schuetz, Alexandra; Krebs, Shelly J; Dewar, Robin; Jagodzinski, Linda; Ubolyam, Sasiwimol; Trichavaroj, Rapee; Tovanabutra, Sodsai; Spudich, Serena; Valcour, Victor; Sereti, Irini; Michael, Nelson; Robb, Merlin; Phanuphak, Praphan; Kim, Jerome H.; Phanuphak, Nittaya

    2016-01-01

    Background The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host. Methods AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag−, HIV IgM−) and Fiebig II–IV (HIV-RNA+, p24 Ag + or −, HIV IgM− or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART. Results Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 vs. 190 copies/106 cells) and gut (0 vs. 898 copies/106 cells), and lower HIV-RNA in blood (4.2 vs. 6.2 log10 copies/mL), gut (1.7 vs. 3.1 log10 copies/mg) and cerebrospinal fluid (2.0 vs. 3.8 log10 copies/mL), when compared to Fiebig II–IV individuals (all P<0.01). Median plasma sCD14 level was lower (1.1 vs. 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 vs. 14.9%, both P<0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I vs. 0.5 pg/mL in Fiebig II–IV, P>0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 vs. 2.6%, P>0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 vs. 340 cells/mm3 and 1.1 vs. 0.7, respectively (both P<0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II–IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (P=0.02). Conclusions Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood

  14. Progress with viral vectored malaria vaccines: A multi-stage approach involving “unnatural immunity”

    PubMed Central

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

    2015-01-01

    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. PMID:26476366

  15. 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. PMID:26476366

  16. Continuous ambulatory peritoneal dialysis and survival of HIV infected patients with end-stage renal disease.

    PubMed

    Kimmel, P L; Umana, W O; Simmens, S J; Watson, J; Bosch, J P

    1993-08-01

    As the number of human immunodeficiency virus (HIV) infected patients has increased in the U.S., the number of infected patients treated for end-stage renal disease (ESRD) has stabilized at about 1 to 2% of the hemodialyzed population. Little has been written regarding the role of continuous ambulatory peritoneal dialysis (CAPD) in the treatment of HIV infected patients with ESRD. To evaluate the effectiveness of CAPD as a long term therapy for HIV infected patients with ESRD, we reviewed our ESRD program's experience. We entered 392 patients from its inception in February 1984 until April 1992. Thirty-one, or 7.9% of our population were HIV infected. Twenty, or 64.5% had stage IV infection. Patients were entered into our chronic hemodialysis (HD) or CAPD program according to standard clinical criteria. Eight HIV infected patients elected to start CAPD, while 23 patients were treated exclusively with HD. The proportion of stage IV infected patients was similar in both treatment modality groups. HIV infected ESRD patients were younger than non-HIV infected patients (37.5 +/- 9.7 vs. 49.8 +/- 15.7 years, respectively, P < 0.0001) at the start of treatment. We used Cox regression techniques to analyze survival data. Mean survival time for our entire non-HIV infected ESRD population (N = 361) was 44.0 +/- 33.9 months. Mean survival time for HIV infected patients with ESRD was 15.5 +/- 9.9 months. Median survival for HIV infected ESRD patients was 13 months compared to 38 months for the non-infected population. As expected, mean survival time in HIV infected ESRD patients was significantly diminished compared to non-infected ESRD patients (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8377381

  17. Immunocompetence of chickens during early and tumorigenic stages of Rous-associated virus-1 infection.

    PubMed Central

    Fadly, A M; Lee, L F; Bacon, L D

    1982-01-01

    A study was designed to determine the effects of congenital infection with the Rous-associated virus-1 (RAV-1) on the immune function chickens during the early and late tumorigenic stages of infection. In another experiment, the effects of niridazole on the immune competence and the tumor incidence in chickens congenitally infected with RAV-1 were studied. Lymphocyte stimulation by phytohemagglutinin, the phytohemagglutinin skin test, the response to immunization with sheep erythrocytes and Brucella abortus, and histological evaluation of lymphoid organs were used to determine the immune competence in normal and infected chickens. Results indicated that both B- and T-cell immune functions during the early and late stages of RAV-1 infection were comparable to those of normal uninfected chickens. Administration of niridazole to congenitally infected chickens at 5 weeks of age for 7 or 21 days had no effect on the T-cell-mediated immunity; however, administration of the drug for 21 days eliminated lymphoma development. Unlike infection with other oncogenic viruses such as those causing Marek's disease and reticuloendotheliosis, infection with RAV-1 caused no detectable immunodepression during the early and late stages of infection. PMID:6290392

  18. Reorganization of Nuclear Pore Complexes and the Lamina in Late-Stage Parvovirus Infection.

    PubMed

    Mäntylä, Elina; Niskanen, Einari A; Ihalainen, Teemu O; Vihinen-Ranta, Maija

    2015-11-01

    Canine parvovirus (CPV) infection induces reorganization of nuclear structures. Our studies indicated that late-stage infection induces accumulation of nuclear pore complexes (NPCs) and lamin B1 concomitantly with a decrease of lamin A/C levels on the apical side of the nucleus. Newly formed CPV capsids are located in close proximity to NPCs on the apical side. These results suggest that parvoviruses cause apical enrichment of NPCs and reorganization of nuclear lamina, presumably to facilitate the late-stage infection. PMID:26311881

  19. Reorganization of Nuclear Pore Complexes and the Lamina in Late-Stage Parvovirus Infection

    PubMed Central

    Mäntylä, Elina; Niskanen, Einari A.; Ihalainen, Teemu O.

    2015-01-01

    Canine parvovirus (CPV) infection induces reorganization of nuclear structures. Our studies indicated that late-stage infection induces accumulation of nuclear pore complexes (NPCs) and lamin B1 concomitantly with a decrease of lamin A/C levels on the apical side of the nucleus. Newly formed CPV capsids are located in close proximity to NPCs on the apical side. These results suggest that parvoviruses cause apical enrichment of NPCs and reorganization of nuclear lamina, presumably to facilitate the late-stage infection. PMID:26311881

  20. 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.

  1. HIV Transmission by Stage of Infection and Pattern of Sexual Partnerships

    PubMed Central

    Kim, Jong-Hoon; Riolo, Rick L.; Koopman, James S.

    2010-01-01

    Background Most model analyses examining the role of primary HIV infection in the HIV epidemic ignore the fact that HIV is often transmitted through long-term, concurrent sexual partnerships. We sought to understand how duration and concurrency of sexual partnerships affect the role of transmissions during primary HIV infection. Methods We constructed a stochastic individual-based model of HIV transmission in a homogeneous population where partnerships form and dissolve. Using observed contagiousness by stage of HIV infection, the fraction of transmissions during primary HIV infection at equilibrium was examined across varying partnership durations and concurrencies. Results The fraction of transmissions during primary HIV infection has a U-shaped relationship with partnership duration. The fraction drops with increasing partnership duration for partnerships with shorter average duration but rises for partnerships with longer average duration. Partnership concurrency modifies this relationship. The fraction of transmissions during primary HIV infection increases with increasing partnership concurrency for partnerships with shorter average duration, but decreases for partnerships with longer average duration. Conclusions Partnership patterns strongly influence the transmission of HIV and do so differentially by stage of infection. Dynamic partnerships need to be taken into account to make a robust inference on the role of different stages of HIV infection. PMID:20571409

  2. Two-stage revision of implant-associated infections after total hip and knee arthroplasty

    PubMed Central

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

    2011-01-01

    Septic loosening of total hip and knee endoprostheses gains an increasing proportion of revision arthroplasties. Operative revisions of infected endoprostheses are mentally and physically wearing for the patient, challenging for the surgeon and a significant economic burden for healthcare systems. In cases of early infection within the first three weeks after implantation a one-stage revision with leaving the implant in place is widely accepted. The recommendations for the management of late infections vary by far. One-stage revisions as well as two-stage or multiple revision schedules have been reported to be successful in over 90% of all cases for certain patient collectives. But implant associated infection still remains a severe complication. Moreover, the management of late endoprosthetic infection requires specific logistics, sufficient and standardized treatment protocol, qualified manpower as well as an efficient quality management. With regard to the literature and experience of specialized orthopaedic surgeons from several university and regional hospitals we modified a commonly used treatment protocol for two-stage revision of infected total hip and knee endoprostheses. In addition to the achievement of maximum survival rate of the revision implants an optimisation of the functional outcome of the affected artificial joint is aimed for. PMID:22242098

  3. 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. PMID:9335187

  4. 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. PMID:26822990

  5. One-stage revision in two cases of Salmonella prosthetic hip infection

    PubMed Central

    Jeroense, Kimberly TV; Kuiper, Jesse WP; Colen, Sascha; Schade, Rogier P; Saouti, Rachid

    2014-01-01

    We describe two cases of prosthetic joint infection (PJI) of the hip due to Salmonella. The first patient presented with an early infection 5 d after being discharged following a total hip replacement and the second patient presented at the emergency ward with a late infection, thirteen years following a total hip replacement. Both cases occurred within one month of each other at our institution and both were successfully treated with a one-stage revision. PJI caused by Salmonella species is very rare: so far only 20 Salmonella PJIs of the hip have been described. Therefore, full consensus on the best treatment approach has not yet been reached. An aggressive two-stage approach is advised because of the virulence of Salmonella, although a limited number of successful one-stage approaches have been described as well. According to the latest guidelines, one-stage revision has comparable success rates and less morbidity compared to two-stage treatment, when selecting the right patients. In our opinion, PJI caused by Salmonella should be treated just as PJI caused by other bacteria, with consideration of the selection criteria as mentioned in several treatment guidelines. As illustrated by these two cases, one-stage revision can be successful in both early and late Salmonella PJI of the hip. PMID:25032209

  6. Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes.

    PubMed

    Udomsangpetch, Rachanee; Pipitaporn, Busaba; Silamut, Kamolrat; Pinches, Robert; Kyes, Sue; Looareesuwan, Sornchai; Newbold, Christopher; White, Nicholas J

    2002-09-01

    In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37 degrees C, but after heating to febrile temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance. PMID:12177447

  7. An investigation of menopausal stage and symptoms on cognition in HIV-infected women

    PubMed Central

    Rubin, Leah H.; Sundermann, Erin E.; Cook, Judith A.; Martin, Eileen M.; Golub, Elizabeth T.; Weber, Kathleen M.; Cohen, Mardge H.; Crystal, Howard; Cederbaum, Julie A.; Anastos, Kathyrn; Young, Mary; Greenblatt, Ruth M.; Maki, Pauline M.

    2014-01-01

    Objective: We evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and HIV infection on cognition. We hypothesized that HIV-infected, perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition. Methods: This cross-sectional study included 708 HIV-infected and 278 HIV-uninfected, pre-, peri-, or postmenopausal women (64% African-American; median age 44 years) from the Women’s Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms. Results: In multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (p’s<0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (p’s<0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (p’s<0.05). Vasomotor symptoms were associated with worse attention (p<0.05). HIV and anxiety symptoms interacted to influence verbal learning (p’s<0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only. Conclusion: Vasomotor, depressive, and anxiety symptoms, but not menopausal stage, were associated with worse cognitive performance in both HIV-infected and uninfected women, although elevated anxiety symptoms were associated with verbal learning deficits more in HIV-infected women. Since cognitive problems can interfere with everyday functioning including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women. PMID:24496085

  8. 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. PMID:26082312

  9. Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.

    PubMed

    Ng, Shengyong; March, Sandra; Galstian, Ani; Hanson, Kirsten; Carvalho, Tânia; Mota, Maria M; Bhatia, Sangeeta N

    2014-02-01

    Homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. In vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. Existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possibly due to missing microenvironmental support signals. One cue that could influence the infection capacity of cultured human hepatocytes is the dissolved oxygen concentration. We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells to model liver-stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium parasite development in vivo correlates with hepatic sinusoidal oxygen gradients. Therefore, we hypothesized that in vitro liver-stage malaria infection efficiencies might improve under hypoxia. Using the infection of micropatterned co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum as a model, we observed that ambient hypoxia resulted in increased survival of exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in a subset of surviving EEFs, based on EEF size. Further, the effective cell surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a mathematical model, were systematically perturbed by varying culture parameters such as hepatocyte density and height of the medium, uncovering an optimal cell surface pO2 to maximize the number of mature EEFs. Initial mechanistic experiments revealed that treatment of primary human hepatocytes with the hypoxia mimetic, cobalt(II) chloride, as well as a HIF-1

  10. 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. PMID:26801599

  11. TLTF in Cerebrospinal Fluid for Detection and Staging of T. b. gambiense Infection

    PubMed Central

    Abdulla, Maha-Hamadien; Bakhiet, Moiz; Lejon, Veerle; Andersson, Jan; McKerrow, James; Al-Obeed, Omar; Harris, Robert A.

    2013-01-01

    Background Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-γ production. Methodology/Principal findings TLTF and anti-TLTF antibodies were assessed in sera and cerebrospinal fluid (CSF) from patients infected with Trypanosoma brucei gambiense (T. b. gambiense) in an attempt to identify alternative markers for diagnosis and stage determination of human African trypanosomiasis or sleeping sickness. Seventy-four serum and sixty-one CSF samples from patients with parasitologically confirmed infection and known disease stage along with 13 sera and CSF from uninfected controls were tested. In serum the levels of anti-TLTF antibodies were unrelated to the disease stage. In contrast, levels of anti-TLTF antibodies in CSF were higher in intermediate/late stages than in early stage disease patients. Specificity of the detected antibodies was assessed by inhibition of TLTF bioactivity as represented by its ability to induce IFN-γ production. Additionally, TLTF was detected in CSF from late stage patients by Western blotting with the anti-TLTF specific monoclonal antibody MO3. Conclusions/Significance These findings suggest a new possibility for disease diagnosis with focus on involvement of the CNS through detection of TLTF and anti-TLTF antibodies in the CSF. PMID:24260185

  12. 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. PMID:26081592

  13. Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

    PubMed Central

    Kunutsor, Setor K.; Whitehouse, Michael R.; Blom, Ashley W.; Beswick, Andrew D.

    2015-01-01

    Background The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain. Objective To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome. Design Systematic review and meta-analysis. Data Sources MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators. Study Selection Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified. Review Methods Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics. Results In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies. Conclusion Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual

  14. Re-Infection Outcomes Following One- And Two-Stage Surgical Revision of Infected Knee Prosthesis: A Systematic Review and Meta-Analysis

    PubMed Central

    Kunutsor, Setor K.; Whitehouse, Michael R.; Lenguerrand, Erik; Blom, Ashley W.; Beswick, Andrew D.

    2016-01-01

    Background Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the most effective for treating periprosthetic knee infection. The one-stage revision strategy is an emerging alternative option, however, its performance in comparison to the two-stage strategy is unclear. We therefore sought to ask if there was a difference in re-infection rates and other clinical outcomes when comparing the one-stage to the two-stage revision strategy. Objective Our first objective was to compare re-infection (new and recurrent infections) rates for one- and two-stage revision surgery for periprosthetic knee infection. Our second objective was to compare between the two revision strategies, clinical outcomes as measured by postoperative Knee Society Knee score, Knee Society Function score, Hospital for Special Surgery knee score, WOMAC score, and range of motion. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, Web of Science, Cochrane Library, reference lists of relevant studies to August 2015, and correspondence with investigators. Study selection Longitudinal (prospective or retrospective cohort) studies conducted in generally unselected patients with periprosthetic knee infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision surgery. No clinical trials comparing both revision strategies were identified. Review methods Two independent investigators extracted data and discrepancies were resolved by consensus with a third investigator. Re-infection rates from 10 one-stage studies (423 participants) and 108 two-stage studies (5,129 participants) were meta-analysed using random-effect models after arcsine transformation. Results The rate (95% confidence intervals) of re-infection was 7.6% (3.4–13.1) in one-stage studies. The corresponding re-infection rate for two-stage revision

  15. ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development.

    PubMed

    Sahu, Tejram; Boisson, Bertrand; Lacroix, Céline; Bischoff, Emmanuel; Richier, Quentin; Formaglio, Pauline; Thiberge, Sabine; Dobrescu, Irina; Ménard, Robert; Baldacci, Patricia

    2014-11-01

    The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria. PMID:25257508

  16. ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development

    PubMed Central

    Sahu, Tejram; Boisson, Bertrand; Lacroix, Céline; Bischoff, Emmanuel; Richier, Quentin; Formaglio, Pauline; Thiberge, Sabine; Dobrescu, Irina; Ménard, Robert; Baldacci, Patricia

    2014-01-01

    The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria. PMID:25257508

  17. 2-stage revision recommended for treatment of fungal hip and knee prosthetic joint infections

    PubMed Central

    2013-01-01

    Background and purpose Fungal prosthetic joint infections are rare and difficult to treat. This systematic review was conducted to determine outcome and to give treatment recommendations. Patients and methods After an extensive search of the literature, 164 patients treated for fungal hip or knee prosthetic joint infection (PJI) were reviewed. This included 8 patients from our own institutions. Results Most patients presented with pain (78%) and swelling (65%). In 68% of the patients, 1 or more risk factors for fungal PJI were found. In 51% of the patients, radiographs showed signs of loosening of the arthroplasty. Candida species were cultured from most patients (88%). In 21% of all patients, fungal culture results were first considered to be contamination. There was co-infection with bacteria in 33% of the patients. For outcome analysis, 119 patients had an adequate follow-up of at least 2 years. Staged revision was the treatment performed most often, with the highest success rate (85%). Interpretation Fungal PJI resembles chronic bacterial PJI. For diagnosis, multiple samples and prolonged culturing are essential. Fungal species should be considered to be pathogens. Co-infection with bacteria should be treated with additional antibacterial agents. We found no evidence that 1-stage revision, debridement, antibiotics, irrigation, and retention (DAIR) or antifungal therapy without surgical treatment adequately controls fungal PJI. Thus, staged revision should be the standard treatment for fungal PJI. After resection of the prosthesis, we recommend systemic antifungal treatment for at least 6 weeks—and until there are no clinical signs of infection and blood infection markers have normalized. Then reimplantation can be performed. PMID:24171675

  18. Evaluation of immuno diagnostic assay for the exposure of stage specific filarial infection.

    PubMed

    Ravishankaran, Rajendran; Shridharan, Radhika Nagamangalam; Vishal, Lawrence Ansel; Meenakshisundaram, Sankaranarayanan; Karande, Anjali Anoop; Kaliraj, Perumal

    2016-03-01

    Lymphatic filariasis is a debilitating diseases caused by filarial parasitic nematodes. The infection may be acquired in childhood but the symptoms become apparent only in later life. To evaluate the success of any intervention, sensitive diagnostics were used to identify infection among endemic normals that are likely to develop microfilaremia in due course of time. Capture assay was standardized using the recombinant protein Brugia malayi Abundant Larval Transcript-2 (ALT-2) specific monoclonal and poly-clonal antibodies and evaluated with serum samples of clinical groups from high and low filarial infection area individuals (HIA/LIA), Endemic Normal (EN, n = 478), microfilaeremics (MF, n = 77), chronic pathology (CP, n = 57) and non endemic normal (NEN, n = 20). In order to assess stage-specific infection, ALT-2 capture assay was compared with the early reported Venom allergen homologue (VAH) and microfilariae specific SXP-1 capture assays. Of the 632 serum samples tested, ALT-2 and VAH capture assays detected circulating filarial antigen (CFA) in 57% and 52% of HIA-EN individuals, respectively. As expected, the VAH and SXP-1 capture assays were positive for 100 % of MF individuals. The described capture assays can be useful for the detection of early and stage-specific filarial infections in endemic regions of developing countries. PMID:27078646

  19. 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

  20. 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

    2016-05-01

    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. PMID:26711542

  1. Low Infection Rates in Total Knee Arthroplasty in End Stage Renal Failure Patients.

    PubMed

    Ling, Zhixing Marcus; Soong, Jun Wei; Loh, Bryan; Yeo, Seng Jin; Pang, Hee Nee; Lo, Ngai Nung

    2016-01-01

    End stage renal failure is considered a risk factor for postoperative infection and many surgeons are cautious in offering this group of patients total knee arthroplasty for symptomatic osteoarthritis. In this retrospective study, 16 total knee arthroplasties were performed in 13 patients and each case was followed up for an average of 5.1 years. We report no cases of infection and also an overall improvement in multiple validated outcome measures. There were, however, 2 cases of periprosthetic loosening. As the patients in our series were generally younger and none was diagnosed with stroke or peripheral vascular disease at the time of surgery, we believe that careful patient selection is key to reducing infection rates in this challenging group of patients. PMID:26282498

  2. Transcriptome Analysis of the Initial Stage of Acute WSSV Infection Caused by Temperature Change

    PubMed Central

    Sun, Yumiao; Li, Fuhua; Sun, Zheng; Zhang, Xiaojun; Li, Shihao; Zhang, Chengsong; Xiang, Jianhai

    2014-01-01

    White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide. Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS). In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C. To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control. Group T didn’t suffer WSSV infection but was subjected to temperature rising in parallel. At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated. Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated. Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression. Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed. Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies. PMID:24595043

  3. Host and parasite thermal acclimation responses depend on the stage of infection.

    PubMed

    Altman, Karie A; Paull, Sara H; Johnson, Pieter T J; Golembieski, Michelle N; Stephens, Jeffrey P; LaFonte, Bryan E; Raffel, Thomas R

    2016-07-01

    Global climate change is expected to alter patterns of temperature variability, which could influence species interactions including parasitism. Species interactions can be difficult to predict in variable-temperature environments because of thermal acclimation responses, i.e. physiological changes that allow organisms to adjust to a new temperature following a temperature shift. The goal of this study was to determine how thermal acclimation influences host resistance to infection and to test for parasite acclimation responses, which might differ from host responses in important ways. We tested predictions of three, non-mutually exclusive hypotheses regarding thermal acclimation effects on infection of green frog tadpoles (Lithobates clamitans) by the trematode parasite Ribeiroia ondatrae with fully replicated controlled-temperature experiments. Trematodes or tadpoles were independently acclimated to a range of 'acclimation temperatures' prior to shifting them to new 'performance temperatures' for experimental infections. Trematodes that were acclimated to intermediate temperatures (19-22 °C) had greater encystment success across temperatures than either cold- or warm-acclimated trematodes. However, host acclimation responses varied depending on the stage of infection (encystment vs. clearance): warm- (22-28 °C) and cold-acclimated (13-19 °C) tadpoles had fewer parasites encyst at warm and cold performance temperatures, respectively, whereas intermediate-acclimated tadpoles (19-25 °C) cleared the greatest proportion of parasites in the week following exposure. These results suggest that tadpoles use different immune mechanisms to resist different stages of trematode infection, and that each set of mechanisms has unique responses to temperature variability. Our results highlight the importance of considering thermal responses of both parasites and hosts when predicting disease patterns in variable-temperature environments. PMID:27040618

  4. Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus.

    PubMed

    Pomaznoy, Mikhail Yu; Logacheva, Maria D; Young, Neil D; Penin, Aleksey A; Ershov, Nikita I; Katokhin, Alexey V; Mordvinov, Viatcheslav A

    2016-02-01

    Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a causative agent of the infection called opisthorchiasis or liver fluke infection. Being a close relative of Opisthorchis viverrini and Clonorchis sinensis (oriental liver flukes) it is encountered in northern Eurasia, especially in Russia, Kazakhstan, Belarus, Ukraine, and Baltic countries. Whole genome data for oriental liver flukes revealed their adaptations for life in the bile duct but our knowledge of O. felineus is scarce. To address this knowledge gap and uncover evolutionary aspect of the adaptations on the transcriptomic level, we used RNA-sequencing approach to investigate two stages of the parasite residing in different hosts. Bioinformatic analysis revealed specific features affecting various biochemical pathways and gene networks. Namely, we observed the loss of genes involved in polyamine synthesis, methionine salvage and peroxisome biogenesis. Some of the gene families, like MD-2 lipid binding proteins, calmodulins and cathepsins on the contrary have expanded compared to free living eukaryotes. We identified significant differences between the stages in homeodomain-containing genes, G-protein coupled receptors, and neuroactive signaling systems. Granulin-like growth factors specific for O. felineus were also identified. In this work, we provide the first whole transcriptome investigation of this parasite. We also hope that these results will create a background for further molecular research of helminth infections and opisthorchiasis in particular. PMID:26363139

  5. Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

    PubMed Central

    Calzavara-Silva, Carlos E.; Gomes, Ana L. V.; Brito, Carlos A. A.; Cordeiro, Marli T.; Silva, Ana M.; Magalhães, Cecilia; Andrade, Raoni; Gil, Laura H. V. G.; Marques, Ernesto T. A.

    2009-01-01

    Background We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. PMID:19936257

  6. 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

  7. 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

  8. Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease.

    PubMed

    Moltó, José; Graterol, Fredzzia; Miranda, Cristina; Khoo, Saye; Bancu, Ioana; Amara, Alieu; Bonjoch, Anna; Clotet, Bonaventura

    2016-04-01

    Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.). PMID:26856824

  9. 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

  10. Species- and infective stage-specific monoclonal antibodies to Leishmania major produced by an in vitro immunization method.

    PubMed

    Wu, S J; Rowton, E D; Ma, M; Andre, R G

    1990-12-01

    Monoclonal antibodies specific to the infective-stage promastigotes of Leishmania major are needed for developing rapid diagnostic assays of infected sand flies. An in vitro immunization protocol was applied for the production of monoclonal antibodies using small amounts of L. major. Infective-stage promastigotes were isolated from sand flies (Phlebotomus papatasi) 7-10 days after infection and used as antigen for immunization. Two weeks after a primary immunization, murine splenocytes were removed and immunized in vitro with antigen in murine EL-4 thymoma cell conditioned medium. Three fusions were performed using X63-Ag.653 myeloma cells as fusion partners and two fusions were performed using FOX-NY cells. Antibodies specific to promastigotes were detected using an indirect enzyme-linked immunosorbent assay (ELISA). Initially 56 monoclonal antibodies were selected, and their species and stage specificity were determined using both an ELISA and an indirect fluorescent antibody assay (IFA). Twelve monoclonal antibodies showed species specificity to L. major when tested against four sympatric species of Leishmania. Four other monoclonal antibodies showed species and infective-stage specificity to L. major promastigotes. When tested in immunoblots, all four species- and stage-specific monoclonal antibodies bound to five protein bands that were unique to the infective-stage promastigotes. PMID:2087235

  11. Transcriptome Analysis of the SL221 Cells at the Early Stage during Spodoptera litura Nucleopolyhedrovirus Infection

    PubMed Central

    Yu, Qian; Xiong, Youhua; Liu, Jianliang; Wen, Dongling; Wu, Xiaohui; Yin, Hanqi

    2016-01-01

    Spodoptera litura (S. litura) is one of the most destructive agricultural pests worldwide. There is urgent need for a nuclear polyhedrosis virus that is specific to S. litura. To date, there have been no reports regarding the responses of S. litura cells to early Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection due to the lack of a reference genome and transcriptome for S. litura. In this study, a cell transcriptome from the host S. litura was assembled and used for Illumina strand-specific RNA sequencing (RNA-seq) to generate 99180 unigenes, representing the 18 hour infection cycle. More than 2000 S. litura genes were significant differentially regulated throughout the infection. The levels of viral mRNAs began to increase dramatically at 6 hpi, and this increase continued throughout the remainder of the infection. We focused on the expression of genes related to stress responses, apoptosis, metabolic enzymes and host cell innate immune system. A small subset of genes related to host stress response, especially for 62 ones being able to annotated as enzyme, ligand and receptor genes, were observed to be specifically differentially expressed at 6 hpi. At 18 hpi, 104 unigenes were continuously significantly changing from 0 hpi to 18 hpi, considered to be viral multiplication related genes, including 3 annotated SL221 unigenes and 81 viral genes, such as tetraspanin and iap gene. This information and further studies on the regulation of host gene expression by baculovirus infection at early stage will provide the tools needed to enhance the utility of this virus as an effective insecticide. PMID:26840182

  12. Regular production of infective sporozoites of Plasmodium falciparum and P. vivax in laboratory-bred Anopheles albimanus.

    PubMed

    Hurtado, S; Salas, M L; Romero, J F; Zapata, J C; Ortiz, H; Arevalo-Herrera, M; Herrera, S

    1997-01-01

    One of the major constraints for studies on the sporogonic cycle of the parasites causing human malaria, and on the protective efficacy of pre-erythrocytic vaccines, is the scarcity of laboratory-reared Anopheles mosquitoes as a source of infective sporozoites. The aim of the present study was to reproduce the life-cycles of Plasmodium falciparum and P. vivax in the laboratory and so develop the ability to produce infective sporozoites of these two species regularly under laboratory conditions. Colonized Anopheles albimanus, of Buenaventura and Tecojate strains, were infected by feeding either on Plasmodium-infected blood, from human patients or experimentally inoculated Aotus monkeys, or on gametocytes of the P. falciparum NF-54 isolate grown in vitro. The monkeys were infected with the blood stages of a Colombian P. vivax isolate and then, after recovery, with the Santa Lucia strain of P. falciparum from El Salvador. Although both of the mosquito strains used were successfully infected with both parasite species, the Buenaventura strain of mosquito was generally more susceptible to infection than the Tecojate strain, and particularly to infection with the parasites from the patients, who lived where this strain of mosquitoes was originally isolated. Monkeys injected intravenously with the P. vivax sporozoites produced in the mosquitoes developed patent sexual and asexual parasitaemias; the gametocytes that developed could then be used to infect mosquitoes, allowing the development of more sporozoites. However, experimental infections failed to establish after the P. falciparum sporozoites were used to inoculate monkeys. The ability to reproduce the complete life cycle of P. vivax in the laboratory, from human to mosquito and then to monkey, should greatly facilitate many studies on vivax malaria and on the efficacy of candidate malaria vaccines. The availability of the sporogonic cycles of P. falciparum from three different sources should also permit a variety of

  13. TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection

    PubMed Central

    Gonçalves, Lígia Antunes; Rodrigues-Duarte, Lurdes; Rodo, Joana; Vieira de Moraes, Luciana; Marques, Isabel; Penha-Gonçalves, Carlos

    2013-01-01

    Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2−/− Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2−/− mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer–hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite. PMID:24218563

  14. Downregulation of protein kinase PKR activation by porcine reproductive and respiratory syndrome virus at its early stage infection.

    PubMed

    Xiao, Yueqiang; Ma, Zexu; Wang, Rong; Yang, Liping; Nan, Yuchen; Zhang, Yan-Jin

    2016-05-01

    The interferon-induced double-strand RNA activated protein kinase (PKR) plays an important role in antiviral response. The objective of this study was to assess the effect of porcine reproductive and respiratory syndrome virus (PRRSV) on PKR activation. Here we report that PRRSV inhibited PKR activation during its early stage infection of primary pulmonary alveolar macrophages (PAMs). PRRSV infection led to lower level of phosphorylated PKR in comparison with mock-infected cells. The PKR inhibition was sustained until 10h post infection in the presence of polyI:C, a synthetic analog of double-stranded RNA activating PKR. PKR-mediated phosphorylation of the eukaryotic translation initiation factor eIF2α was also lower in the PRRSV-infected PAMs during the early stage infection. Interestingly, inactivated PRRSV was capable to inhibit the PKR activation until 6h post infection. This suggests that structural components of PRRSV virions were responsible for the inhibition, although PRRSV replication was needed for longer inhibition. These results indicate that the downregulation of PKR activation during early infection stage should be essential for PRRSV to avoid the antiviral response to initiate replication. This finding contributes to our understanding on PRRSV interaction with host innate immune response and reveal a target for control of PRRSV infection. PMID:27066702

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

    PubMed

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

    2015-12-01

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

  16. 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. PMID:25772333

  17. Cowpea-Meloidogyne incognita interaction: Root proteomic analysis during early stages of nematode infection.

    PubMed

    Villeth, Gabriela R C; Carmo, Lilian S T; Silva, Luciano P; Fontes, Wagner; Grynberg, Priscila; Saraiva, Mario; Brasileiro, Ana C M; Carneiro, Regina M D; Oliveira, José T A; Grossi-de-Sá, Maria F; Mehta, Angela

    2015-05-01

    Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea is the root-knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2-DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile-specifier protein. A follow-up study was performed by quantitative RT-PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT-PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection. PMID:25736976

  18. Is two-stage reimplantation effective for virulent pathogenic infection in a periprosthetic hip? A retrospective analysis

    PubMed Central

    Yoon, Yong-Cheol; Lakhotia, Devendra; Oh, Jong-Keon; Moon, Jun Gyu; Prashant, Kumar; Shon, Won Yong

    2015-01-01

    AIM: To investigate the effectiveness of two-stage reimplantation using antibiotic-loaded bone cement (ALBC) and the risk factors associated with failure to control periprosthetic joint infection (PJI). METHODS: We retrospectively reviewed 38 consecutive hips managed using two-stage reimplantation with ALBC. The mean follow-up period was 5.4 years (range: 2.5-9 years). RESULTS: The causative pathogens were isolated from 29 patients (76%), 26 of whom were infected with highly virulent organisms. Sixteen patients (42%) underwent at least two first-stage debridements. An increased debridement frequency correlated significantly with high comorbidity (P < 0.001), a lower preoperative Harris hip score (HHS; P < 0.001), antimicrobial resistance, and gram-negative and polymicrobial infection (P = 0.002). Of the 35 patients who underwent two-stage reimplantation, 34 showed no signs of recurrence of infection. The mean HHS improved from 46 ± 12.64 to 78 ± 10.55 points, with 7 (20%), 12 (34%), 11 (32%) and 5 (14%) patients receiving excellent, good, fair and poor ratings, respectively. CONCLUSION: The current study demonstrated that two-stage reimplantation could successfully treat PJI after hip arthroplasty. However, the ability of ALBC to eradicate infection was limited because frequent debridement was required in high-risk patients (i.e., patients who are either in poor general health due to associated comorbidities or harbor infections due to highly virulent, difficult-to-treat organisms). Level of evidence: Level IV. PMID:26495248

  19. 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. PMID:24559522

  20. Dissecting host factors that regulate the early stages of tuberculosis infection.

    PubMed

    Agrawal, Neha; Bhattacharyya, Chandrika; Mukherjee, Ankur; Ullah, Ubaid; Pandit, Bhaswati; Rao, Kanury V S; Majumder, Partha P

    2016-09-01

    Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-α and IFN-γ secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the Gi-protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation. PMID:27553417

  1. Diagnosis of dengue infection using various diagnostic tests in the early stage of illness.

    PubMed

    Lolekha, Rangsima; Chokephaibulkit, Kulkanya; Yoksan, Sutee; Vanprapar, Nirun; Phongsamart, Wanatpreeya; Chearskul, Sanay

    2004-06-01

    In order to elucidate the usefulness of various tests in the early course of dengue infection, in terms of diagnosis and correlation with clinical severity, blood specimens were collected every 48 hours on 3 occasions from patients with clinical suspicion of dengue infection with fever for less than 4 days. Viral isolation was attempted by mosquito inoculation (MI), tissue culture inoculation (TC), and reverse transcriptase polymerase chain reaction (RT-PCR). Antibodies were detected by hemagglutination inhibition test (HI), an in-house-ELISA (IH-ELISA), and an ELISA by MRL diagnostics Clinical data were collected from the time of enrollment to complete recovery. Of the 40 patients enrolled, 31 were diagnosed as dengue infection and confirmed by either serology or viral isolation. Of these, 12 had primary infection and 19 had secondary infection. Dengue fever occurred in 9 cases. Dengue viruses were isolated from 28 out of 31 patients, and dengue hemorrhagic fever was diagnosed in 22 patients. Viral serotypes identified by viral isolation, and RT-PCR were concordant: DEN1 was isolated in 8, DEN2 in 13, DEN3 in 5, and DEN4 in 2 patients. Viral isolation yielded positive results on blood collected before the 5th day of fever. MI was more sensitive than TC. RT-PCR was less sensitive than viral isolation during the early days of fever, but became more sensitive after the 5th day of fever. RT-PCR was able to detect virus up to day 7-8 of fever, even after defervescence, and in the presence of antibody. During the febrile stage, serological diagnosis on blood samples taken 48 hours apart was carried out by HI, IH-ELISA, and MRL-ELISA, facilitating diagnosis in 3 (10%), 21 (67%), and 27 (87%) of patients, respectively. All of the patients with secondary infection were diagnosed by MRL-ELISA before defervescence. By the 8th day of fever, a serological diagnosis aided to diagnose in 9 (29%), 29 (93%), and 31 (100%) of patients by HI, IH-ELISA, and MRL-ELISA, respectively

  2. Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections.

    PubMed

    Ramalhete, Cátia; da Cruz, Filipa P; Lopes, Dinora; Mulhovo, Silva; Rosário, Virgílio E; Prudêncio, Miguel; Ferreira, Maria-José U

    2011-12-15

    Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita-5,24-diene-3β,23(R)-diol-7-O-β-D-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods including 2D-NMR experiments (COSY, HMQC, HMBC and NOESY). Compounds 1-6, were evaluated for their antimalarial activity against the erythrocytic stages of the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Assessment of compounds (1-3 and 5, 6) activity against the liver stage of Plasmodium berghei was also performed, measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luc(con). Active compounds were shown to inhibit the parasite's intracellular development rather than its ability to invade hepatic cells. Toxicity of compounds (1-3 and 5, 6) was assessed on the same cell line and on mouse primary hepatocytes through the fluorescence measurement of cell confluency. Furthermore, toxicity of compounds 1-6 towards human cells was also investigated in the MCF-7 breast cancer cell line, showing that they were not toxic or exhibited weak toxicity. In blood stages of P. falciparum, compounds 1-5 displayed antimalarial activity, revealing triacetylbalsaminol F (5) the highest antiplasmodial effects (IC(50) values: 0.4μM, 3D7; 0.2μM, Dd2). The highest antiplasmodial activity against the liver stages of P.berghei was also displayed by compound 5, with high inhibitory activity and no toxicity. PMID:22071523

  3. Nocardia prosthetic knee infection successfully treated by one-stage exchange: case report and review.

    PubMed

    Laurent, F; Rodriguez-Villalobos, H; Cornu, O; Vandercam, B; Yombi, J C

    2015-08-01

    A 64-year-old man with a history of sarcoidosis on corticosteroids and azathioprine was admitted to our hospital with complaints of worsening left knee pain and swelling for the past 3 weeks. His past medical history is also significant for severe osteoarthritis requiring a cemented total left knee arthroplasty 1 year ago. Diagnostic investigation during his hospital admission eventually led to the diagnosis of Nocardia nova knee prosthetic joint infection in the setting of a disseminated nocardiosis. He was successful treated by one-stage complete hardware exchange in conjunction with an adapted antibiotic therapy regimen (meropenem and doxycycline followed by ceftriaxone and doxycycline). Two years later, his recovery was deemed excellent. PMID:25560058

  4. Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection.

    PubMed

    Lee, Chia Min; Weight, Alisha K; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M; Chen, Jianzhu

    2012-12-11

    Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

  5. Plasmacytoid dendritic cells sequester high prion titres at early stages of prion infection.

    PubMed

    Castro-Seoane, Rocio; Hummerich, Holger; Sweeting, Trevor; Tattum, M Howard; Linehan, Jacqueline M; Fernandez de Marco, Mar; Brandner, Sebastian; Collinge, John; Klöhn, Peter-Christian

    2012-02-01

    In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with

  6. Two-Stage Procedure for Infected Aortic Graft Pseudoaneurysm: 10-Year Follow Up after Omental Prosthesis Wrapping.

    PubMed

    von Aspern, Konstantin; Etz, Christian D; Mohr, Friedrich W; Battellini, Roberto R

    2015-08-01

    Prosthetic graft infections with mediastinitis following aortic surgery are rare, yet represent grave complications yielding high morbidity and mortality. We present the case of a 57-year-old female patient with past history of emergent surgery for iatrogenic Type A dissection treated by supracoronary ascending aortic replacement. Four months after the initial surgery, a sternal fistula had formed and due to severe bleeding emergent reoperation was required. Imaging and pathology on admission revealed an infected pseudoaneurysm at the distal aortic prosthesis and mediastinitis with methicillin-resistant Staphylococcus aureus. Rescue surgery was performed by means of a two-stage approach, with extensive debridement, graft replacement and continuous antiseptic lavage in a first step and an omental wrapping of the new prosthesis in a second stage 24 hours later. During 10 years of follow-up, no recurrent infection occurred. The operative approach and general considerations for management of infected pseudoaneurysms are discussed. PMID:27069945

  7. In Vitro Alterations Do Not Reflect a Requirement for Host Cell Cycle Progression during Plasmodium Liver Stage Infection

    PubMed Central

    Hanson, Kirsten K.; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N.

    2014-01-01

    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. PMID:25416236

  8. 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...

  9. Automated system for characterization and classification of malaria-infected stages using light microscopic images of thin blood smears.

    PubMed

    Das, D K; Maiti, A K; Chakraborty, C

    2015-03-01

    In this paper, we propose a comprehensive image characterization cum classification framework for malaria-infected stage detection using microscopic images of thin blood smears. The methodology mainly includes microscopic imaging of Leishman stained blood slides, noise reduction and illumination correction, erythrocyte segmentation, feature selection followed by machine classification. Amongst three-image segmentation algorithms (namely, rule-based, Chan-Vese-based and marker-controlled watershed methods), marker-controlled watershed technique provides better boundary detection of erythrocytes specially in overlapping situations. Microscopic features at intensity, texture and morphology levels are extracted to discriminate infected and noninfected erythrocytes. In order to achieve subgroup of potential features, feature selection techniques, namely, F-statistic and information gain criteria are considered here for ranking. Finally, five different classifiers, namely, Naive Bayes, multilayer perceptron neural network, logistic regression, classification and regression tree (CART), RBF neural network have been trained and tested by 888 erythrocytes (infected and noninfected) for each features' subset. Performance evaluation of the proposed methodology shows that multilayer perceptron network provides higher accuracy for malaria-infected erythrocytes recognition and infected stage classification. Results show that top 90 features ranked by F-statistic (specificity: 98.64%, sensitivity: 100%, PPV: 99.73% and overall accuracy: 96.84%) and top 60 features ranked by information gain provides better results (specificity: 97.29%, sensitivity: 100%, PPV: 99.46% and overall accuracy: 96.73%) for malaria-infected stage classification. PMID:25523795

  10. 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. PMID:27329138

  11. Differentially proteomic analysis of the Chinese shrimp at WSSV latent and acute infection stages by iTRAQ approach.

    PubMed

    Li, Shihao; Li, Fuhua; Sun, Zheng; Zhang, Xiaojun; Xiang, Jianhai

    2016-07-01

    As the direct executors of biological function, the expression level of proteins will reveal the molecular mechanisms regulating WSSV acute infection more directly. In the present study, the iTRAQ approach was applied to identifying differentially expressed proteins in Chinese shrimp during WSSV latent infection and acute infection. A total of 4051 unique peptides corresponding to 1286 proteins were identified. 118 unique proteins showed differential up-regulation and 122 proteins were down-regulated in shrimp during WSSV acute infection compared with those in WSSV latent infection stage. A number of proteins related to actin-myosin cytoskeleton process, including myosin, actin, tubulin, clathrin, and tropomyosin were found up-regulated in shrimp at WSSV AI stage, indicating that the phagocytosis process was involved in WSSV AI stage. The apoptosis process in shrimp during WSSV AI seemed to be inhibited because some proteins suppressive on apoptosis were up-regulated, such as ALG-2 interacting protein x, Hsp90, 14-3-3-like protein, peroxiredoxin 5, peroxiredoxin 6 and adenine nucleotide translocase 2. Association analysis between the proteomic data and the previous transcriptome data was performed. Quantitative real-time PCR and western blot were carried out to verify the reliability of the proteomics data. The present study provided a comprehensive view of molecular mechanisms regulating WSSV acute infection at the protein level. PMID:27192146

  12. Use of a New Knee Prosthesis as an Articulating Spacer in Two-Stage Revision of Infected Total Knee Arthroplasty

    PubMed Central

    Fabrin, Jesper; Poulsen, Klaus; Schroder, Henrik Morville

    2016-01-01

    Purpose To report our experience with two-stage revision using a new femoral component (NFC) spacer (Depuy Synthes) as an articulating spacer. Materials and Methods In this retrospective study, we reviewed 22 two-stage revisions that were performed using an NFC spacer in 22 patients suspected of having an infected total knee arthroplasty (TKA) from December 2010 to March 2013. The result was considered successful when eradication of infection was achieved using only one NFC spacer. Results The average time from primary TKA to the first stage procedure was 29.1 months and the average time from the first stage procedure until the final second stage procedure was 12.7 weeks. The average range of motion increased from 82° preoperatively to 104° postoperatively. The American Knee Society Knee score increased from 29.3 points to 66 points. The Function score increased from 29.5 points to 64 points. Four cases were reinfected after two-stage revision. The mean follow-up was 37.6 months. Conclusions The new articulating spacer showed promising short-term results both with regard to eradication of infection and functional improvement. PMID:27595079

  13. Autoclaved metal-on-cement spacer versus static spacer in two-stage revision in periprosthetic knee infection

    PubMed Central

    Chen, Yu-Pin; Wu, Cheng-Chun; Ho, Wei-Pin

    2016-01-01

    Background: Periprosthetic knee infection is troublesome for Orthopedic surgeons and a catastrophy for patients. Reported rates of periprosthetic joint infection following primary total knee arthroplasty (TKA) are 0.39–2%. Two stage revision arthroplasty, which has success rates exceeding 90%, has been the gold standard for treating subacute and chronic periprosthetic infection following TKA. Antibiotic spacers, a well established means of delivering local antibiotic therapy, maintain soft tissue tension during two stage revision arthroplasty. However, controversy remains around whether static or mobile antibiotic impregnated spacers are superior for treating infection following TKA. Various mobile spacers are available, including cement-on-cement, cement-on-polyethylene and metal-on-polyethylene. In this study, the efficacy of the modified metal-on-cement spacer, consisting of reinsertion of the autoclaved femoral component and implantation of antibiotic-loaded cement in the proximal tibia, is assessed. Materials and Methods: Records of 19 patients diagnosed as periprosthetic knee infection were reviewed in this retrospective study. Among these patients, 10 patients received first stage debridement with the autoclaved metal-on-cement spacer and 8 patients with the static spacer, who eventually underwent two-stage re-implantation, were listed in the final comparison. Patient demographics, infection eradication rates, average range of motion (ROM), surgical time and blood loss during the second-stage of the surgery, and Knee Society (KS) knee scores at last followup after revision total knee replacement were clinically evaluated. Results: At a minimum of 2-year followup after re-implantation, infection eradication rates, surgical times, blood loss during the second-stage of the surgery, and KS knee score after re-implantation were similar for the two groups. Patients receiving autoclaved metal-on-cement spacers had superior ROM after re-implantation compared to

  14. Prevalence and intensity of infection with third stage larvae of Angiostrongylus cantonensis in mollusks from Northeast Thailand.

    PubMed

    Tesana, Smarn; Srisawangwong, Tuanchai; Sithithaworn, Paiboon; Laha, Thewarach; Andrews, Ross

    2009-06-01

    Prevalences and intensity of infection with Angiostrongylus cantonensis third stage larvae were examined in mollusks to determine whether they are potential intermediate hosts in eight provinces, northeast Thailand. Mollusk samples were collected from 24 reservoirs (3 reservoirs/province) in close to human cases during the previous year. Six out of 24 localities and 9 (3 new record species) out of 27 species were found with the infection. The highest intensity in infected species was found to be only one or two snails, whereas the majority had very low or no infection. The highest density was found in Pila pesmei and the lowest in Pila polita. The edible snails, P. polita, P. pesmei, and Hemiplecta distincta have the potential to transmit A. cantonensis to man. The varying density levels of larvae in infected snails may reflect observed variation in symptoms of people who traditionally eat a raw snail dish. PMID:19478262

  15. 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 ...

  16. CD40 is required for protective immunity against liver stage Plasmodium infection1

    PubMed Central

    Murray, Sara A; Mohar, Isaac; Miller, Jessica L; Brempelis, Katherine J; Vaughan, Ashley M; Kappe, Stefan HI; Crispe, Ian N

    2015-01-01

    The co-stimulatory molecule CD40 enhances immunity through several distinct roles in T cell activation and T cell interaction with other immune cells. In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8+ T cells in the liver, and protective immunity induced by immunization with the P. yoelii fabb/f- genetically attenuated parasite. Using mixed adoptive transfers of polyclonal wild type (WT) and CD40-deficient (CD40−/−) CD8+ T cells into WT and CD40−/− hosts, we evaluated the contributions to CD8+ T cell immunity of CD40 expressed on host tissues including antigen-presenting cells (APC), compared to CD40 expressed on the CD8+ T cells themselves. Most of the effects of CD40 could be accounted for by expression in the T cells’ environment, including the accumulation of large numbers of CD8+ T cells in the livers of immunized mice. Thus, protective immunity generated during immunization with fabb/f- was largely dependent on effective APC licensing via CD40 signaling. PMID:25646303

  17. 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.

  18. The Modified Static Spacers Using Antibiotic-Impregnated Cement Rod in Two-Stage Revision for Infected Total Knee Arthroplasty

    PubMed Central

    Yoo, Juhyung; Lee, Seungyup; Han, Changdong

    2011-01-01

    The two-stage exchange arthroplasty (one- or two-stage) is believed to be the gold standard for the management of infections following total knee arthroplasty. We herein report a novel two-stage exchange arthroplasty technique using an antibiotic-impregnated cement intramedullary nail, which can be easily prepared during surgery using a straight thoracic tube and a Steinmann pin, and may provide additional stability to the knee to maintain normal mechanical axis. In addition, there is less pain between the period of prosthesis removal and subsequent reimplantation. Less soft tissue contracture, less scar adhesion, easy removal of the cement intramedullary nail, and successful infection control are the advantages of this technique. PMID:21909473

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

    PubMed

    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

  20. 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

  1. Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens.

    PubMed

    Ateba-Ngoa, Ulysse; Jones, Sophie; Zinsou, Jeannot Fréjus; Honkpehedji, Josiane; Adegnika, Ayola Akim; Agobe, Jean-Claude Dejon; Massinga-Loembe, Marguerite; Mordmüller, Benjamin; Bousema, Teun; Yazdanbakhsh, Maria

    2016-08-01

    Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium-infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity. PMID:27273645

  2. 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.

  3. Two-stage reimplantation in infected total knee arthroplasty using a re-sterilized tibial polyethylene insert and femoral component.

    PubMed

    Lee, Jin Kyu; Choi, Choong H

    2012-10-01

    Infection in total knee arthroplasty (TKA) is a challenging complication. We reviewed 20 cases of infected TKAs treated by two-stage reimplantation procedure involving the use of a temporary articulating system composed of autoclaved femoral component, low temperature hydrogen peroxide gas plasma sterilized polyethylene insert, and antibiotic-impregnated bone cement. The knee and functional score of the Knee Society scoring system at the last follow (average, 64.8 months) up was 86.2 points and 78.8 points. The success rate in terms of eradication of infection was 95% (19/20 knees). Use of a temporary articulating system composed of the re-sterilized components with antibiotic-impregnated bone cement was an effective therapy not only for the eradication of the infection but also for the recovery of soft tissue health and knee function. PMID:22503405

  4. One-stage reconstruction with open bone grafting and vacuum-assisted closure for infected tibial non-union

    PubMed Central

    Deng, Zhouming; Jin, Wei; Ping, Ansong; Wei, Renxiong

    2013-01-01

    Introduction Non-union of the tibia complicated by osteomyelitis is one of the most challenging problems in orthopaedic surgery. There remains a significant amount of debate and controversy regarding the optimal medical management of infected tibial non-union. There are few articles which have reported the outcomes of treatment for infected non-union of tibia from single-stage reconstruction with open bone grafting plus vacuum-assisted closure (VAC). Material and methods Our report covers experience between March 2007 and February 2010 of open bone grafting plus VAC in one stage for patients with infected tibial non-union. The time for bone union and wound healing to occur, the duration of hospitalisation, and the rate of resolution of infection were all analysed. The main outcome measures were based on a clinical scoring system that assessed functional ability, range of knee and ankle motion, shortening, infection and pain. Fifteen patients were involved in this study. Results All patients were followed up for an average of 22.6 months (range: 14–42 months). Bone union was achieved in 93.3% (14/15) of patients after a mean of 5.93 months (range: 3–10 months). All wounds healed within an average period of 5 weeks (range: 3–10 weeks), and the function and appearance of all limbs were satisfactory. Conclusions Open bone grafting combined with VAC in a one-stage procedure can be a feasible alternative to the treatment of infected tibial non-union, especially for those wounds which are not good candidates for microsurgery; however, further studies are required to confirm the likely benefits. PMID:25276163

  5. 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.

  6. Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice.

    PubMed

    Sousa, L M A; Carneiro, M B H; Resende, M E; Martins, L S; Dos Santos, L M; Vaz, L G; Mello, P S; Mosser, D M; Oliveira, M A P; Vieira, L Q

    2014-01-01

    Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice. PMID:24102495

  7. Short interfering RNA-mediated gene silencing in Globodera pallida and Meloidogyne incognita infective stage juveniles.

    PubMed

    Dalzell, Johnathan J; McMaster, Steven; Fleming, Colin C; Maule, Aaron G

    2010-01-01

    The analysis of gene function through RNA interference (RNAi)-based reverse genetics in plant parasitic nematodes (PPNs) remains inexplicably reliant on the use of long double-stranded RNA (dsRNA) silencing triggers; a practice inherently disadvantageous due to the introduction of superfluous dsRNA sequence, increasing chances of aberrant or off-target gene silencing through interactions between nascent short interfering RNAs (siRNAs) and non-cognate mRNA targets. Recently, we have shown that non-nematode, long dsRNAs have a propensity to elicit profound impacts on the phenotype and migrational abilities of both root knot and cyst nematodes. This study presents, to our knowledge for the first time, gene-specific knockdown of FMRFamide-like peptide (flp) transcripts, using discrete 21bp siRNAs in potato cyst nematode Globodera pallida, and root knot nematode Meloidogyne incognita infective (J2) stage juveniles. Both knockdown at the transcript level through quantitative (q)PCR analysis and functional data derived from migration assay, indicate that siRNAs targeting certain areas of the FMRFamide-like peptide (FLP) transcripts are potent and specific in the silencing of gene function. In addition, we present a method of manipulating siRNA activity through the management of strand thermodynamics. Initial evaluation of strand thermodynamics as a determinant of RNA-Induced Silencing Complex (RISC) strand selection (inferred from knockdown efficacy) in the siRNAs presented here suggested that the purported influence of 5' stand stability on guide incorporation may be somewhat promiscuous. However, we have found that on strategically incorporating base mismatches in the sense strand of a G. pallida-specific siRNA, we could specifically increase or decrease the knockdown of its target (specific to the antisense strand), presumably through creating more favourable thermodynamic profiles for incorporation of either the sense (non-target-specific) or antisense (target

  8. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

    PubMed

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-08-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  9. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection

    PubMed Central

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-01-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  10. 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.

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

    PubMed Central

    Winkler, Heinz

    2009-01-01

    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

  12. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review

    PubMed Central

    Aguirre Valadez, Jonathan; García Juárez, Ignacio; Rincón Pedrero, Rodolfo; Torre, Aldo

    2015-01-01

    Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation. PMID:25767389

  13. Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection.

    PubMed

    Nigam, Pragati; Kwa, Suefen; Velu, Vijayakumar; Amara, Rama Rao

    2011-01-15

    Progressive disease caused by pathogenic SIV/HIV infections is marked by systemic hyperimmune activation, immune dysregulation, and profound depletion of CD4(+) T cells in lymphoid and gastrointestinal mucosal tissues. IL-17 is important for protective immunity against extracellular bacterial infections at mucosa and for maintenance of mucosal barrier. Although IL-17-secreting CD4 (Th17) and CD8 (Tc17) T cells have been reported, very little is known about the latter subset for any infectious disease. In this study, we characterized the anatomical distribution, phenotype, and functional quality of Tc17 and Th17 cells in healthy (SIV-) and SIV+ rhesus macaques. In healthy macaques, Tc17 and Th17 cells were present in all lymphoid and gastrointestinal tissues studied with predominance in small intestine. About 50% of these cells coexpressed TNF-α and IL-2. Notably, ∼50% of Tc17 cells also expressed the co-inhibitory molecule CTLA-4, and only a minority (<20%) expressed granzyme B suggesting that these cells possess more of a regulatory than cytotoxic phenotype. After SIV infection, unlike Th17 cells, Tc17 cells were not depleted during the acute phase of infection. However, the frequency of Tc17 cells in SIV-infected macaques with AIDS was lower compared with that in healthy macaques demonstrating the loss of these cells during end-stage disease. Antiretroviral therapy partially restored the frequency of Tc17 and Th17 cells in the colorectal mucosa. Depletion of Tc17 cells was not observed in colorectal mucosa of chronically infected SIV+ sooty mangabeys. In conclusion, our results suggest a role for Tc17 cells in regulating disease progression during pathogenic SIV infection. PMID:21148794

  14. 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 Central

    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.

    2014-01-01

    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. PMID:24854165

  15. Interleukin-15 production at the early stage after oral infection with Listeria monocytogenes in mice

    PubMed Central

    MITANI, A; NISHIMURA, H; HIROSE, K; WASHIZU, J; KIMURA, Y; TANAKA, S; YAMAMOTO, G; NOGUCHI, T; YOSHIKAI, Y

    1999-01-01

    We previously reported that exogenous interleukin-15 (IL-15) induces proliferation and activation of intestinal intraepithelial lymphocytes (i-IEL) in naive mice. To investigate the ability of endogenous IL-15 to stimulate i-IEL in vivo, we monitored i-IEL and intestinal epithelial cells (i-EC) in mice after an oral infection with Listeria monocytogenes. Although the populations of αβ and γδ i-IEL were not significantly changed after the oral infection, the expression level of interferon-γ (IFN-γ) was increased both at transcriptional and protein levels, and a conversely marked decrease in interleukin-4 (IL-4) was detected in the i-IEL on day 1 after infection as compared with before infection. The T helper 1 (Th1)-biased response of i-IEL coincided with a peak response of IL-15 production in the i-EC after oral infection. These results suggested that IL-15 produced from i-EC may be at least partly involved in the stimulation of i-IEL to produce IFN-γ after oral infection with L. monocytogenes. PMID:10447719

  16. 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

  17. 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. PMID:27289435

  18. Recognition of Stage-Specific Mycobacterial Antigens Differentiates between Acute and Latent Infections with Mycobacterium tuberculosis

    PubMed Central

    Demissie, Abebech; Leyten, Eliane M. S.; Abebe, Markos; Wassie, Liya; Aseffa, Abraham; Abate, Getahun; Fletcher, Helen; Owiafe, Patrick; Hill, Philip C.; Brookes, Roger; Rook, Graham; Zumla, Alimuddin; Arend, Sandra M.; Klein, Michel; Ottenhoff, Tom H. M.; Andersen, Peter; Doherty, T. Mark

    2006-01-01

    Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or α-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB. PMID:16467323

  19. Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection

    PubMed Central

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  20. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    PubMed

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  1. Serologic markers in early stages of African horse sickness virus infection.

    PubMed

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1997-02-01

    Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection. PMID:9003637

  2. 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.

  3. Stage-specific regulation of natural killer cell homeostasis and response against viral infection by microRNA-155

    PubMed Central

    Zawislak, Carolyn L.; Beaulieu, Aimee M.; Loeb, Gabriel B.; Karo, Jenny; Canner, David; Bezman, Natalie A.; Lanier, Lewis L.; Rudensky, Alexander Y.; Sun, Joseph C.

    2013-01-01

    Natural killer (NK) cells function in the recognition and destruction of host cells infected with pathogens. Many regulatory mechanisms govern the potent responses of NK cells, both at the cellular and molecular level. Ablation of microRNA (miRNA) processing enzymes demonstrated that miRNAs play critical roles in NK cell differentiation and function; however, the role of individual miRNAs requires further investigation. Using mice containing a targeted deletion of microRNA-155 (miR-155), we observed defects in NK cell maintenance and maturation at steady state, as well as in homeostatic proliferation in lymphopenic mice. In addition, we discovered that miR-155 is up-regulated in activated NK cells during mouse cytomegalovirus (MCMV) infection in response to signals from the proinflammatory cytokines IL-12 and IL-18 and through signal transducer and activator of transcription 4 (STAT4) signaling. Although miR-155 was found to be dispensable for cytotoxicity and cytokine production when triggered through activating receptors, NK cells lacking miR-155 exhibited severely impaired effector and memory cell numbers in both lymphoid and nonlymphoid tissues after MCMV infection. We demonstrate that miR-155 differentially targets Noxa and suppressor of cytokine signaling 1 (SOCS1) in NK cells at distinct stages of homeostasis and activation. NK cells constitutively expressing Noxa and SOCS1 exhibit profound defects in expansion during the response to MCMV infection, suggesting that their regulation by miR-155 promotes antiviral immunity. PMID:23572582

  4. Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks

    PubMed Central

    Thompson, Robin N.; Gilligan, Christopher A.; Cunniffe, Nik J.

    2016-01-01

    We assess how presymptomatic infection affects predictability of infectious disease epidemics. We focus on whether or not a major outbreak (i.e. an epidemic that will go on to infect a large number of individuals) can be predicted reliably soon after initial cases of disease have appeared within a population. For emerging epidemics, significant time and effort is spent recording symptomatic cases. Scientific attention has often focused on improving statistical methodologies to estimate disease transmission parameters from these data. Here we show that, even if symptomatic cases are recorded perfectly, and disease spread parameters are estimated exactly, it is impossible to estimate the probability of a major outbreak without ambiguity. Our results therefore provide an upper bound on the accuracy of forecasts of major outbreaks that are constructed using data on symptomatic cases alone. Accurate prediction of whether or not an epidemic will occur requires records of symptomatic individuals to be supplemented with data concerning the true infection status of apparently uninfected individuals. To forecast likely future behavior in the earliest stages of an emerging outbreak, it is therefore vital to develop and deploy accurate diagnostic tests that can determine whether asymptomatic individuals are actually uninfected, or instead are infected but just do not yet show detectable symptoms. PMID:27046030

  5. Monocyte chemotactic protein-1 secretion and expression after Toxoplasma gondii infection in vitro depend on the stage of the parasite.

    PubMed

    Brenier-Pinchart, Marie-Pierre; Vigan, Inés; Jouvin-Marche, Evelyne; Marche, Patrice Noél; Pelet, Elisabeth; Gross, Uwe; Ambroise-Thomas, Pierre; Pelloux, Hervé

    2002-08-27

    Infection of human fibroblasts with tachyzoites of RH and Prugniaud strains, two different strains of Toxoplasma gondii, significantly increased monocyte chemotactic protein (MCP)-1 secretion contrary to what happened with bradyzoites of the cystogenetic strain. Quantification of MCP-1 mRNA by RT-PCR showed that this phenomenon is regulated at the transcriptional level. Thus, the stage of parasite can be deciding in MCP-1 induction since only tachyzoites induced MCP-1 expression and secretion. MCP-1 induced by tachyzoites could be involved in cell recruitment, as shown by the quantification of MCP1 ARNm by real-time PCR (LightCycler, Roche Diagnostics), in the pathogenesis of T. gondii infection. PMID:12204371

  6. 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. PMID:25913888

  7. 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...

  8. The physiology of infection with nematodes: the role of intracellular pH in the development of the early parasitic stage.

    PubMed

    Petronijevic, T; Rogers, W P

    1987-01-01

    1. H2CO3, the host's signal which induced (less than 25 min) the Ca2+-dependent development of the first parasitic stage of Haemonchus contortus, produced a diphasic change in the pHi (less than 30 min), measured with 5,5-dimethyl-2,4-oxazolidinedione, in the infective stage. The intensity of the diphasic change was related to the [H2CO3] and so to the efficiency of the stimulus for development. 2. MES and HEPES buffers induced a rapid rise in pHi of infective stages in step with pHo. Ortho-and pyrophosphate induced greater changes in pHi. Such buffers did not initiate development. 3. These and other results suggest that the stimulus for development, H2CO3, induced an energy-dependent Ca2+/H+ exchange mediated by mitochondria of the infective stage, which initiated development of the parasitic stage. PMID:2890466

  9. Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells.

    PubMed

    Zeng, Xuehuo; Carlin, Cathleen R

    2013-02-01

    Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lysosomal degradation pathway for recycling intracellular components that is upregulated during periods of cell stress. Autophagic cargo is sequestered in double-membrane structures called autophagosomes that fuse with endosomes to form amphisomes which then deliver their content to lysosomes. Autophagy is an important adaptive response in airway epithelial cells targeted by many common adenovirus serotypes. Using two established tissue culture models, we demonstrate here that adaptive autophagy enhances expression of the early region 1 adenovirus protein, induction of mitogen-activated protein kinase signaling, and production of new viral progeny in airway epithelial cells infected with adenovirus type 2. We have also discovered that adenovirus infections are tightly regulated by endosome maturation, a process characterized by abrupt exchange of Rab5 and Rab7 GTPases, associated with early and late endosomes, respectively. Moreover, endosome maturation appears to control a pool of early endosomes capable of fusing with autophagosomes which enhance adenovirus infection. Many viruses have evolved mechanisms to induce autophagy in order to aid their own replication. Our studies reveal a novel role for host cell autophagy that could have a significant impact on the outcome of respiratory infections. PMID:23236070

  10. Soluble cell adhesion molecules in human Chagas' disease: association with disease severity and stage of infection.

    PubMed

    Laucella, S; De Titto, E H; Segura, E L; Orn, A; Rottenberg, M E

    1996-12-01

    Formation of inflammatory lesions, one of the pathologic consequences of infection with Trypanosoma cruzi, involves intricate cell-cell interactions in which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease patients grouped according to disease severity were studied for the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1), soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if they could be used alone or in different combinations as markers for specific diagnostic procedures. Comparisons were made between congenitally, acutely, and chronically infected patients and aged-matched, noninfected individuals, as well as between patients with chronic Chagas' disease grouped according to the severity of their heart-related pathology. No differences in levels of s-CAMs were detected between sera from children with congenital T. cruzi infection and sera from noninfected infants born from chagasic mothers. In contrast, titers of s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were significantly increased in sera from patients during the acute phase of infection with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically infected patients. A positive association with disease severity in sera from patients with chronic disease was observed for the levels of s-P-selectin. In contrast, we found no association between clinical symptoms and levels of s-VCAM-1. Patients with chronic disease with severe cardiopathy also showed diminished levels of s-CD44 in comparison with healthy controls or patients with mild disease. The results are discussed in the context of pathology of Chagas' disease. PMID:9025689

  11. The JAK-STAT Pathway Controls Plasmodium vivax Load in Early Stages of Anopheles aquasalis Infection

    PubMed Central

    Bahia, Ana C.; Kubota, Marina S.; Tempone, Antonio J.; Araújo, Helena R. C.; Guedes, Bruno A. M.; Orfanó, Alessandra S.; Tadei, Wanderli P.; Ríos-Velásquez, Claudia M.; Han, Yeon S.; Secundino, Nágila F. C.; Barillas-Mury, Carolina

    2011-01-01

    Malaria affects 300 million people worldwide every year and 450,000 in Brazil. In coastal areas of Brazil, the main malaria vector is Anopheles aquasalis, and Plasmodium vivax is responsible for the majority of malaria cases in the Americas. Insects possess a powerful immune system to combat infections. Three pathways control the insect immune response: Toll, IMD, and JAK-STAT. Here we analyze the immune role of the A. aquasalis JAK-STAT pathway after P. vivax infection. Three genes, the transcription factor Signal Transducers and Activators of Transcription (STAT), the regulatory Protein Inhibitors of Activated STAT (PIAS) and the Nitric Oxide Synthase enzyme (NOS) were characterized. Expression of STAT and PIAS was higher in males than females and in eggs and first instar larvae when compared to larvae and pupae. RNA levels for STAT and PIAS increased 24 and 36 hours (h) after P. vivax challenge. NOS transcription increased 36 h post infection (hpi) while this protein was already detected in some midgut epithelial cells 24 hpi. Imunocytochemistry experiments using specific antibodies showed that in non-infected insects STAT and PIAS were found mostly in the fat body, while in infected mosquitoes the proteins were found in other body tissues. The knockdown of STAT by RNAi increased the number of oocysts in the midgut of A. aquasalis. This is the first clear evidence for the involvement of a specific immune pathway in the interaction of the Brazilian malaria vector A. aquasalis with P. vivax, delineating a potential target for the future development of disease controlling strategies. PMID:22069502

  12. The JAK-STAT pathway controls Plasmodium vivax load in early stages of Anopheles aquasalis infection.

    PubMed

    Bahia, Ana C; Kubota, Marina S; Tempone, Antonio J; Araújo, Helena R C; Guedes, Bruno A M; Orfanó, Alessandra S; Tadei, Wanderli P; Ríos-Velásquez, Claudia M; Han, Yeon S; Secundino, Nágila F C; Barillas-Mury, Carolina; Pimenta, Paulo F P; Traub-Csekö, Yara M

    2011-11-01

    Malaria affects 300 million people worldwide every year and 450,000 in Brazil. In coastal areas of Brazil, the main malaria vector is Anopheles aquasalis, and Plasmodium vivax is responsible for the majority of malaria cases in the Americas. Insects possess a powerful immune system to combat infections. Three pathways control the insect immune response: Toll, IMD, and JAK-STAT. Here we analyze the immune role of the A. aquasalis JAK-STAT pathway after P. vivax infection. Three genes, the transcription factor Signal Transducers and Activators of Transcription (STAT), the regulatory Protein Inhibitors of Activated STAT (PIAS) and the Nitric Oxide Synthase enzyme (NOS) were characterized. Expression of STAT and PIAS was higher in males than females and in eggs and first instar larvae when compared to larvae and pupae. RNA levels for STAT and PIAS increased 24 and 36 hours (h) after P. vivax challenge. NOS transcription increased 36 h post infection (hpi) while this protein was already detected in some midgut epithelial cells 24 hpi. Imunocytochemistry experiments using specific antibodies showed that in non-infected insects STAT and PIAS were found mostly in the fat body, while in infected mosquitoes the proteins were found in other body tissues. The knockdown of STAT by RNAi increased the number of oocysts in the midgut of A. aquasalis. This is the first clear evidence for the involvement of a specific immune pathway in the interaction of the Brazilian malaria vector A. aquasalis with P. vivax, delineating a potential target for the future development of disease controlling strategies. PMID:22069502

  13. Transovarial Transmission Efficiency of Babesia bovis Tick Stages Acquired by Rhipicephalus (Boophilus) microplus during Acute Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The protozoan parasite Babesia bovis, a reemerging threat to U.S. cattle, is acquired by adult female ticks of the subgenus Boophilus, and is transovarially transmitted as the kinete stage to developing larval offspring. Sporozoites develop within larvae and are transmitted during larval feeding on ...

  14. Antibiotic treatment of Lyme disease. Current recommendations by stage and extent of infection.

    PubMed

    Rahn, D W

    1992-05-15

    Much has been learned about Lyme disease over the past several years, but much remains to be learned. Careful clinical observation has led to elucidation of the natural history of this disease, and further clinical observations are needed to unravel the remaining areas of uncertainty. It is by no means clear that all the symptoms attributed to Lyme disease today actually represent true manifestations of Borrelia burgdorferi infection or that patients with well-documented Lyme disease whose symptoms do not respond to antibiotic therapy have persistent infection. Immunologically mediated mechanisms may be responsible for the chronic disease manifestations that seem so resistant to antibiotics. Uncovering answers to these questions requires the close collaboration of astute practicing physicians and biomedical scientists working together for their patients' benefit. PMID:1589368

  15. 2-Hexadecynoic Acid Inhibits Plasmodial FAS-II Enzymes and Arrest Erythrocytic and Liver Stage Plasmodium Infections

    PubMed Central

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L.; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H.; Brun, Reto; Carballeira, Néstor M.

    2010-01-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of P. yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC50 value 6.6. μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescense analysis (IC50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory against the PfFAS-II enzymes PfFabI and PfFabZ with IC50 values of 0.38 and 0.58 μg/ml (IC50 control drugs 14 and 30 ng/ml) respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC50 values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC50 20.2 μg/ml), and Leishmania donovani (IC50 values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature and calculated pharmacokinetic properties suggest that 2-HDA could be a useful compound to study the interaction of fatty

  16. 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

  17. Parasite distribution and early-stage encephalitis in Sarcocystis calchasi infections in domestic pigeons (Columba livia f. domestica).

    PubMed

    Maier, Kristina; Olias, Philipp; Enderlein, Dirk; Klopfleisch, Robert; Mayr, Sylvia L; Gruber, Achim D; Lierz, Michael

    2015-01-01

    Pigeon protozoal encephalitis is a biphasic, neurologic disease of domestic pigeons (Columba livia f. domestica) caused by the apicomplexan parasite Sarcocystis calchasi. Despite severe inflammatory lesions of the brain, associated parasitic stages have only rarely been identified and the cause of the lesions is still unclear. The aim of this study was therefore to characterize the tissue distribution of S. calchasi within pigeons between the two clinical phases and during the occurrence of neurological signs. For this purpose, a semi-quantitative real-time polymerase chain reaction (PCR) was developed. Forty-five domestic pigeons were infected orally (via a cannula into the crop) with 200 S. calchasi sporocysts and euthanized in groups of three pigeons at intervals of 2 to 10 days over a period of 61 days. Tissue samples including brain and skeletal muscle were examined by histology, immunohistochemistry, and PCR. Schizonts were detected in the liver of one pigeon at day 10 post infection. A mild encephalitis was detected at day 20 post infection, around 4 weeks before the onset of neurological signs. At the same time, immature sarcocysts were present in the skeletal muscle. In seven pigeons a few sarcocysts were identified in the brain, but not associated with any lesion. These results suggest that the encephalitis is induced at a very early stage of the S. calchasi lifecycle rather than in the chronic phase of pigeon protozoal encephalitis. Despite the increasing severity of lesions in the central nervous system, the amount of sarcocysts did not increase. This supports the hypothesis of a delayed-type hypersensitivity response as the cause of the encephalitis. The study also demonstrated that S. calchasi DNA is detectable in tissues negative by histological methods, indicating a higher sensitivity of the real-time PCR. PMID:25338141

  18. 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

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

    PubMed

    Zhuang, Jianguo; Gao, Peng; 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, [Formula: see text], 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

  20. 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

    2016-01-01

    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. PMID:26864744

  1. Fighting while parasitized: can nematode infections affect the outcome of staged combat in beetles?

    PubMed

    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

  2. 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.

  3. CD8+ T Cells Mediate Robust Stage-Specific Immunity to P. berghei under Chemoprophylaxis and This Protective Environment Is Not Downregulated by the Presence of Blood-Stage Infection

    PubMed Central

    Heiss, Kirsten; Mueller, Ann-Kristin

    2014-01-01

    Sterile protection against malaria infection can be achieved by the inoculation of intact sporozoites while treating concomitantly with the 4-aminoquinoline chloroquine. We present an analysis of protective immunity elicited by successive immunization with Plasmodium berghei sporozoites under chemoprophylaxis. Immunization resulted in a protective, stage-specific immune response. Protection appeared to be mediated by CD8+ T cells and was abrogated upon their specific depletion. Adoptive transfer of splenocytes rendered recipient animals resistant to sporozoite infection, but not to blood-stage challenge. Immunization with sporozoites under chemoprophylaxis results in robust immunity, and the presence of blood-stage infection at sporozoite immunization had no downregulating effect on the protective immune response. PMID:24516592

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

    PubMed

    Scandiani, María M; Luque, Alicia G; Razori, María V; Ciancio Casalini, Lucila; Aoki, Takayuki; O'Donnell, Kerry; Cervigni, Gerardo D L; Spampinato, Claudia P

    2015-01-01

    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. tucumaniae. Disease symptoms were scored at 7, 10, 14, and 25 days post-inoculation (dpi). The greatest difference in the area under the disease progress curve (AUDPC) values among genotypes was observed at 25 dpi. In order to detect early metabolic markers that could potentially discriminate between susceptible and resistant genotypes, gas chromatography-mass spectrometry (GC-MS) analyses of root samples were performed. These analyses show higher levels of several amino acids and the polyamine cadaverine in the inoculated than in the uninoculated susceptible cultivar at 7 dpi. Principal component analysis (PCA) revealed that the metabolic profile of roots harvested at the earliest time points from the inoculated susceptible genotype was clearly differentiated from the rest of the samples. Furthermore, variables associated with the first principal component were mainly amino acids. Taken together, the results indicate that the pathogen induced the susceptible plant to accumulate amino acids in roots at early time points after infection, suggesting that GC-MS-based metabolomics could be used for the rapid characterization of cultivar response to SDS. PMID:25336687

  5. Evidence for the expression of actomyosin in the infective stage of the sporozoan protist Eimeria.

    PubMed

    Preston, T M; King, C A

    1992-04-01

    A high-speed supernatant extract was obtained from infective oocysts of Eimeria tenella homogenised in a sucrose-low ionic strength buffer. Immunoblotting showed this soluble, micropore-filtered preparation (designated E1) to be rich in actin. E1 underwent superprecipitation on addition of ATP but not its non-hydrolysable analogue AMP.PMP--behaviour typical of an actomyosin solution. The superprecipitate fluoresced strongly in the presence of rhodamine-phalloidin (indicative of the presence of F-actin) and electron microscopy of negatively-stained preparations of this flocculent matter confirmed the abundance of filamentous material within it. This is the first demonstration of a functional actomyosin isolated from a member of the economically important phylum Apicomplexa. PMID:1525837

  6. 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. PMID:26143866

  7. The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection

    PubMed Central

    van Ooij, Christiaan; Tamez, Pamela; Bhattacharjee, Souvik; Hiller, N. Luisa; Harrison, Travis; Liolios, Konstantinos; Kooij, Taco; Ramesar, Jai; Balu, Bharath; Adams, John; Waters, Andy; Janse, Chris; Haldar, Kasturi

    2008-01-01

    The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful, but additional functional analyses revealed the first conserved secretome function. This gave new insight into mechanisms for the assembly of the parasite-induced tubovesicular network needed for import of nutrients into the infected erythrocyte. Thus, genomic screens combined with functional assays provide unexpected and fundamental insights into host remodeling by this major human pathogen. PMID:18551176

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

    PubMed

    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

  9. 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

  10. Interleukin-6 in two-stage revision arthroplasty: what is the threshold value to exclude persistent infection before re-implanatation?

    PubMed

    Hoell, S; Borgers, L; Gosheger, G; Dieckmann, R; Schulz, D; Gerss, J; Hardes, J

    2015-01-01

    The purpose of this study was to evaluate whether the serum level of interleukin 6 (IL-6) could be used to identify the persistence of infection after the first stage of a two-stage revision for periprosthetic joint infection. Between 2010 and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified in two intra-operative tissue samples during re-implantation in 16 patients. These cases were classified as representing persistent infection. To calculate a precise cut-off value which could be used in everyday clinical practice, a 3 x 2 contingency table was constructed and manually defined. We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8 pg/mL can be regarded as indicating an absence of infection: its negative predictive value is 92.1%. The serum IL-6 level seems to be a reasonable marker for identifying persistent infection after the first stage of a revision joint arthroplasty and before attempting re-implantation. PMID:25568416

  11. Effect of Thai 'koi-hoi' food flavoring on the viability and infectivity of the third-stage larvae of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae).

    PubMed

    Eamsobhana, Praphathip; Yoolek, Adisak; Yong, Hoi-Sen

    2010-03-01

    The effect of the food flavoring of 'koi-hoi', a popular Thai snail dish, on the viability and infectivity of Angiostrongylus (=Parastrongylus) cantonensis third-stage larvae was assessed in a mouse model. Groups of 50 each of actively moving, non-motile coiled, and extended larvae were obtained from experimentally infected snail meat, after one-hour exposure to standard 'koi-hoi' flavoring. These larvae and groups of 50 unexposed moving larvae (control) were individually fed to each group of three experimental BALB/c mice. The effect on Angiostrongylus worm burden was measured after 3 weeks of infection. Infectivity of the motile larvae after exposure to 'koi-hoi' food flavoring was 38 + or - 5.29%. This was highly significantly lower than the infectivity (62 + or - 7.21%) of the control (unexposed) third-stage larvae (chi(2) = 17.28, P < 0.001). In the non-motile larvae resulting from exposure to the food flavoring, no adult worm was recovered from the extended larvae, indicating that they were no longer alive and unable to cause infection. A small proportion (3.33 + or - 2.31%) of the coiled larvae developed into young adult worms, indicating that mobility alone is not a definitive indicator of viability. The present study confirms that the food flavoring components of 'koi-hoi' dish adversely affect the viability and infectivity of A. cantonensis larvae. Exposure of the third-stage larvae to 'koi-hoi' food flavoring resulted in decreased viability and eventually death. Prolonged treatment with food flavoring to inactivate/immobilize and then kill the infective, third-stage larvae of A. cantonensis in snail meat prior to consumption may be one of the possible economical means of reducing human infection. PMID:19931504

  12. Use of a High Resolution Melting (HRM) Assay to Compare Gag, Pol, and Env Diversity in Adults with Different Stages of HIV Infection

    PubMed Central

    Cousins, Matthew M.; Laeyendecker, Oliver; Beauchamp, Geetha; Brookmeyer, Ronald; Towler, William I.; Hudelson, Sarah E.; Khaki, Leila; Koblin, Beryl; Chesney, Margaret; Moore, Richard D.; Kelen, Gabor D.; Coates, Thomas; Celum, Connie; Buchbinder, Susan P.; Seage, George R.; Quinn, Thomas C.; Donnell, Deborah; Eshleman, Susan H.

    2011-01-01

    Background Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual. Methods HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14–540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env. Results Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection. Conclusions The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined. PMID:22073290

  13. An Immediate Innate Immune Response Occurred In the Early Stage of E.granulosus Eggs Infection in Sheep: Evidence from Microarray Analysis

    PubMed Central

    Tang, Jishun; Hou, Hongyan; Chen, Sheng; Jia, Bin; Ban, Qian

    2015-01-01

    Background Cystic Echinococcosis(CE), caused by infection with the larval stage of the cestode Echinococcus granulosus (E. granulosus), is a chronic parasitic zoonosis, with highly susceptible infection in sheep. However, the comprehensive molecular mechanisms that underlie the process of E. granulosus infection in the early stage remain largely unknown. The objective of this present study was to gain a cluster of genes expression profiles in the intestine tissue of sheep infected with CE. Methods Nine healthy sheep were divided into infection group and healthy controls, with six infected perorally 5000 E. granulosus eggs suspended in 1000μl physiological saline and three controls perorally injected 1000μl physiological saline. All animals were sacrificed at 4 hours post-infection, respectively. The intestine tissue was removed and the RNA was extracted. In the infection group, the biology replicates were designed to make sure the accuracy of the data. The ovine microarrays were used to analyze changes of gene expression in the intestine tissue between CE infected sheep and healthy controls. Real-time PCR was used to assess reliability of the microarray data. Results By biology repeats, a total of 195 differentially expressed genes were identified between infected group and controls at 4 hours post-infection, with 105 genes related to immune responses, while 90 genes associated with functions including energy metabolism, fat soluble transport, etc. Among the 105 immunity genes, 72 genes showed up-regulated expression levels while 33 showed down-regulation levels. Function analysis showed that most of up-regulated genes were related to innate immune responses, such as mast cell, NK cell, cytokines, chemokines and complement. In addition, Real-time PCR analysis of a random selection of nine genes confirmed the reliability of the microarray data. Conclusion To our knowledge, this is the first report describing gene expression profiles in the intestine tissue of CE

  14. Cathepsin Gene Family Reveals Transcriptome Patterns Related to the Infective Stages of the Salmon Louse Caligus rogercresseyi

    PubMed Central

    Maldonado-Aguayo, Waleska; Chávez-Mardones, Jacqueline; Gonçalves, Ana Teresa; Gallardo-Escárate, Cristian

    2015-01-01

    Cathepsins are proteases involved in the ability of parasites to overcome and/or modulate host defenses so as to complete their own lifecycle. However, the mechanisms underlying this ability of cathepsins are still poorly understood. One excellent model for identifying and exploring the molecular functions of cathepsins is the marine ectoparasitic copepod Caligus rogercresseyi that currently affects the Chilean salmon industry. Using high-throughput transcriptome sequencing, 56 cathepsin-like sequences were found distributed in five cysteine protease groups (B, F, L, Z, and S) as well as in an aspartic protease group (D). Ontogenic transcriptome analysis evidenced that L cathepsins were the most abundant during the lifecycle, while cathepsins B and K were mostly expressed in the larval stages and adult females, thus suggesting participation in the molting processes and embryonic development, respectively. Interestingly, a variety of cathepsins from groups Z, L, D, B, K, and S were upregulated in the infective stage of copepodid, corroborating the complexity of the processes involved in the parasitic success of this copepod. Putative functional roles of cathepsins were conjectured based on the differential expressions found and on roles previously described in other phylogenetically related species. Moreover, 140 single nucleotide polymorphisms (SNP) were identified in transcripts annotated for cysteine and aspartic proteases located into untranslated regions, or the coding region. This study reports for the first time the presence of cathepsin-like genes and differential expressions throughout a copepod lifecycle. The identification of cathepsins together with functional validations represents a valuable strategy for pinpointing target molecules that could be used in the development of new delousing drugs or vaccines against C. rogercresseyi. PMID:25923525

  15. 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

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

    PubMed

    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

  17. Cathepsin Gene Family Reveals Transcriptome Patterns Related to the Infective Stages of the Salmon Louse Caligus rogercresseyi.

    PubMed

    Maldonado-Aguayo, Waleska; Chávez-Mardones, Jacqueline; Gonçalves, Ana Teresa; Gallardo-Escárate, Cristian

    2015-01-01

    Cathepsins are proteases involved in the ability of parasites to overcome and/or modulate host defenses so as to complete their own lifecycle. However, the mechanisms underlying this ability of cathepsins are still poorly understood. One excellent model for identifying and exploring the molecular functions of cathepsins is the marine ectoparasitic copepod Caligus rogercresseyi that currently affects the Chilean salmon industry. Using high-throughput transcriptome sequencing, 56 cathepsin-like sequences were found distributed in five cysteine protease groups (B, F, L, Z, and S) as well as in an aspartic protease group (D). Ontogenic transcriptome analysis evidenced that L cathepsins were the most abundant during the lifecycle, while cathepsins B and K were mostly expressed in the larval stages and adult females, thus suggesting participation in the molting processes and embryonic development, respectively. Interestingly, a variety of cathepsins from groups Z, L, D, B, K, and S were upregulated in the infective stage of copepodid, corroborating the complexity of the processes involved in the parasitic success of this copepod. Putative functional roles of cathepsins were conjectured based on the differential expressions found and on roles previously described in other phylogenetically related species. Moreover, 140 single nucleotide polymorphisms (SNP) were identified in transcripts annotated for cysteine and aspartic proteases located into untranslated regions, or the coding region. This study reports for the first time the presence of cathepsin-like genes and differential expressions throughout a copepod lifecycle. The identification of cathepsins together with functional validations represents a valuable strategy for pinpointing target molecules that could be used in the development of new delousing drugs or vaccines against C. rogercresseyi. PMID:25923525

  18. 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...

  19. 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...

  20. Evaluation of the therapeutic effect of potassium permanganate at early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of potassium permanganate (KMnO4) against early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus) was evaluated. Fish were experimentally challenged, by waterborne exposure for 2 h to F. columnare after cutaneous abrasion, an...

  1. 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. PMID:27018615

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

    PubMed Central

    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. PMID:26098302

  3. Plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase

    PubMed Central

    2011-01-01

    Background Plasmodium falciparum sporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. Shortly after hepatocyte invasion, the parasite starts to produce Liver Stage Antigen-1 (LSA-1), which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. The LSA-1 protein has been described as a flocculent mass, but its role in parasite development has not been determined. Methods Recombinant N-terminal, C-terminal or a construct containing both the N- and C- terminal regions flanking two 17 amino acid residue central repeat sequences (LSA-NRC) were subjected to in vitro modification by tissue transglutaminase-2 (TG2) to determine if cross-linking occurred. In addition, tissue sections of P. falciparum-infected human hepatocytes were probed with monoclonal antibodies to the isopeptide ε-(γ-glutamyl)lysine cross-bridge formed by TG2 enzymatic activity to determine if these antibodies co-localized with antibodies to LSA-1 in the growing liver schizonts. Results This study identified a substrate motif for (TG2) and a putative casein kinase 2 phosphorylation site within the central repeat region of LSA-1. The function of TG2 is the post-translational modification of proteins by the formation of a unique isopeptide ε-(γ-glutamyl)lysine cross-bridge between glutamine and lysine residues. When recombinant LSA-1 protein was crosslinked in vitro by purified TG2 in a calcium dependent reaction, a flocculent mass of protein was formed that was highly resistant to degradation. The cross-linking was not detectably affected by phosphorylation with plasmodial CK2 in vitro. Monoclonal antibodies specific to the very unique TG2 catalyzed ε- lysine cross-bridge co-localized with antibodies to LSA-1 in infected human hepatocytes providing visual evidence that LSA-1 was cross-linked in vivo. Conclusions While the

  4. Stages of HIV Infection

    MedlinePlus

    ... Disease Dementia Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination ... New Media Tools Blogs Mashups Mobile Office Hours Online Collaboration Tools Photo Sharing Sites Podcasts QR Codes ...

  5. 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

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

    PubMed

    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

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

    PubMed

    Pittman, Kelly J; Knoll, Laura J

    2015-12-01

    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

  8. Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection.

    PubMed

    Thanapati, Subrat; Das, Rumki; Tripathy, Anuradha S

    2015-01-01

    The aim of this study was to characterize NK (CD56(+)CD3(-)) and NKT-like cell (CD56(+)CD3(+)) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30(+)CD3(-)CD56(+), NKp30(+)CD3(+)CD56(+), CD244(+)CD3(-)CD56(+), and CD244(+)CD3(+)CD56(+)cells were high, whereas the percentages of NKG2D(+)CD3(-)CD56(+) and NKG2D(+)CD3(+)CD56(+)cells were low in both patient groups. The percentages of NKp44(+)CD3(-)CD56(+) cells were high in both patient groups, whereas the percentages of NKp44(+)CD3(+)CD56(+) cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46(+)CD3(-)CD56(+) cells were high in both patient groups. Higher percentages of perforin(+)CD3(-)CD56(+) and perforin(+)CD3(+)CD56(+) cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin(+) NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin(+) NK cells in the acute phase and IFN-γ(+) NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection. PMID:26388848

  9. Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection

    PubMed Central

    Thanapati, Subrat; Das, Rumki; Tripathy, Anuradha S.

    2015-01-01

    The aim of this study was to characterize NK (CD56+CD3−) and NKT-like cell (CD56+CD3+) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30+CD3−CD56+, NKp30+CD3+CD56+, CD244+CD3−CD56+, and CD244+CD3+CD56+cells were high, whereas the percentages of NKG2D+CD3−CD56+ and NKG2D+CD3+CD56+cells were low in both patient groups. The percentages of NKp44+CD3−CD56+ cells were high in both patient groups, whereas the percentages of NKp44+CD3+CD56+ cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46+CD3−CD56+ cells were high in both patient groups. Higher percentages of perforin+CD3−CD56+ and perforin+CD3+CD56+ cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin+ NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin+ NK cells in the acute phase and IFN-γ+ NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection. PMID:26388848

  10. A core MRB1 complex component is indispensable for RNA editing in insect and human infective stages of Trypanosoma brucei.

    PubMed

    Ammerman, Michelle L; Tomasello, Danielle L; Faktorová, Drahomíra; Kafková, Lucie; Hashimi, Hassan; Lukeš, Julius; Read, Laurie K

    2013-01-01

    Uridine insertion/deletion RNA editing is a unique and vital process in kinetoplastids, required for creation of translatable open reading frames in most mitochondrially-encoded RNAs. Emerging as a key player in this process is the mitochondrial RNA binding 1 (MRB1) complex. MRB1 comprises an RNA-independent core complex of at least six proteins, including the GAP1/2 guide RNA (gRNA) binding proteins. The core interacts in an RNA-enhanced or -dependent manner with imprecisely defined TbRGG2 subcomplexes, Armadillo protein MRB10130, and additional factors that comprise the dynamic MRB1 complex. Towards understanding MRB1 complex function in RNA editing, we present here functional characterization of the pentein domain-containing MRB1 core protein, MRB11870. Inducible RNAi studies demonstrate that MRB11870 is essential for proliferation of both insect vector and human infective stage T. brucei. MRB11870 ablation causes a massive defect in RNA editing, affecting both pan-edited and minimally edited mRNAs, but does not substantially affect mitochondrial RNA stability or processing of precursor transcripts. The editing defect in MRB1-depleted cells occurs at the initiation stage of editing, as pre-edited mRNAs accumulate. However, the gRNAs that direct editing remain abundant in the knockdown cells. To examine the contribution of MRB11870 to MRB1 macromolecular interactions, we tagged core complexes and analyzed their composition and associated proteins in the presence and absence of MRB11870. These studies demonstrated that MRB11870 is essential for association of GAP1/2 with the core, as well as for interaction of the core with other proteins and subcomplexes. Together, these data support a model in which the MRB1 core mediates functional interaction of gRNAs with the editing machinery, having GAP1/2 as its gRNA binding constituents. MRB11870 is a critical component of the core, essential for its structure and function. PMID:24250748

  11. Efficacy of Single-stage Revision with Aggressive Debridement Using Intra-articular Antibiotics in the Treatment of Infected Joint Prosthesis

    PubMed Central

    Antony, Suresh J; Westbrook, Richard S; Jackson, John S; Heydemann, Jacob S; Nelson, Jenny L

    2015-01-01

    Prosthetic joint infections (PJI) of the hip and knee are uncommon, but result in significant morbidity and mortality when they do occur. Current management consists of a combination of either single- or two-stage exchange of the prosthesis and/or exchange of polymer components with intravenous (IV) antibiotics (4–6 weeks) and intraoperative debridement of the joint prior to reimplantation. However, failure rate, morbidity, and expense associated with current management are high, especially if the infection involves resistant pathogens and/or osteomyelitis. Also, the current use of systemic antibiotics does not allow for high local concentrations of the drug and biofilm penetration of the infected prosthesis. To overcome these difficulties, we examined the outcomes of aggressive operative debridement of the infected prosthesis. This was achieved through the use of a single-stage revision and administration of high concentrations of local intra-articular antibiotics via Hickman catheters. We present 57 patients with PJI who were treated with intra-articular antibiotics and single-stage revisions. Minimal systemic toxicity was observed along with a 100% microbiologic cure rate and 89% without relapse at 11-month follow-up despite isolation of multidrug resistant pathogens. This is the largest study to date using this method in the treatment of PJI. PMID:26279625

  12. Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells.

    PubMed Central

    Chakrabarti, L.; Isola, P.; Cumont, M. C.; Claessens-Maire, M. A.; Hurtrel, M.; Montagnier, L.; Hurtrel, B.

    1994-01-01

    Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellular tropism. The lymph nodes presented a remarkably high viral load during the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, macrophages and T4 lymphocytes were identified by combined immunohistochemistry and in situ hybridization as the target cells of the virus. Simian immunodeficiency virus-positive macrophages concentrated in the subcapsular sinuses, suggesting an entry of infected cells via the afferent lymphatics. A shift in the pattern of viral infection was observed at 2 weeks after inoculation, with a concentration of viral RNA in the germinal centers of the developing lymphoid follicles. Follicular dendritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the virus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection. Images Figure 2 Figure 4 Figure 5 Figure 6 PMID:8203463

  13. Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers

    PubMed Central

    McCarthy, James S.; Baker, Mark; O'Rourke, Peter; Marquart, Louise; Griffin, Paul; Hooft van Huijsduijnen, Rob; Möhrle, Jörg J.

    2016-01-01

    Objectives OZ439, or artefenomel, is an investigational synthetic ozonide antimalarial with similar potency, but a significantly improved pharmacokinetic profile, compared with artemisinins. We wished to measure key pharmacokinetic and pharmacodynamic parameters and the pharmacokinetic/pharmacodynamic relationship of artefenomel in humans to guide the drug's further development as combination therapy in patients. Patients and methods We tested artefenomel in the human induced blood-stage malaria (IBSM) model. Plasmodium infection was monitored by quantitative PCR (qPCR) and upon reaching 1000 parasites/mL single doses of 100, 200 and 500 mg of artefenomel were administered orally with evaluation of drug exposure and parasitaemia until rescue treatment after 16 days or earlier, if required. Results A single 100 mg dose had only a transient effect, while the 200 mg dose resulted in a significant reduction in parasitaemia before early recrudescence. At the highest (500 mg) dose, initial clearance of parasites below the limit of detection of qPCR was observed, with a 48 h parasite reduction ratio (PRR48) >10 000 and a parasite clearance half-life of 3.6 h (95% CI 3.4–3.8 h). However, at this dose, recrudescence was seen in four of eight subjects 6–10 days after treatment. Pharmacokinetic/pharmacodynamic modelling predicted an MIC of 4.1 ng/mL. Conclusions These results confirm the antimalarial potential of artefenomel for use in a single-exposure combination therapy. The observations from this study support and will assist further clinical development of artefenomel. PMID:27272721

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

    PubMed Central

    Raaben, Matthijs; Einerhand, Alexandra WC; Taminiau, Lucas JA; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis AM; Rossen, John WA

    2007-01-01

    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. PMID:17555580

  15. One-stage débridement and knee fusion for infected total knee arthroplasty using the hybrid frame.

    PubMed

    VanRyn, Jacques S; Verebelyi, David M

    2002-01-01

    In 1997 and 1998, a hybrid fixator was used for a one-step arthrodesis in 2 cases of infected total knee arthroplasty. One patient had rheumatoid arthritis, and the other had an infected reimplant arthroplasty. Neither patient was a candidate for reimplantation. Fusions were achieved with the hybrid frame in an average of 10 weeks. All signs of local and systemic infections were eliminated. After 24 months for patient 1 and 37 months for patient 2, both are infection-free and ambulatory without the aid of a wheelchair. PMID:11805940

  16. 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

  17. Clinical disease and stage of lactation influence shedding of Mycobacterium avium subspecies paratuberculosis into milk and colostrum of naturally infected dairy cows.

    PubMed

    Stabel, J R; Bradner, L; Robbe-Austerman, S; Beitz, D C

    2014-10-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of Johne's disease (JD). One mode of transmission of MAP is through ingestion of contaminated milk and colostrum by susceptible calves. The objective of this study was to determine if the amount of MAP shed into the milk and colostrum of infected cows was affected by severity of infection as well as the number of days in milk (DIM). Milk was collected over the 305-d lactation period from naturally infected cows in the asymptomatic subclinical (n=39) and symptomatic clinical (n=29) stages of disease, as well as 8 noninfected control cows. All milk samples were assayed for MAP by culture on Herrold's egg yolk medium and either BACTEC 12B (Becton Dickinson, Franklin Lakes, NJ) or para-JEM (Thermo Fisher Scientific, Trek Diagnostic Systems Inc., Cleveland, OH) liquid medium, and by direct PCR for the IS900 target gene. Mycobacterium avium ssp. paratuberculosis was detected in 3.8, 4.1, and 12.6% of milk samples collected from cows with subclinical JD after culture in Herrold's egg yolk medium, liquid medium, and direct PCR, respectively. The frequency of MAP positivity increased to 12.9, 18.4, and 49.2% of milk samples collected from cows with clinical JD by these same methods, respectively. None of the milk samples collected from control cows was positive for MAP by any detection method. Viable MAP was primarily isolated from milk and colostrum of subclinically and clinically infected cows collected in early lactation (DIM 0-60), with negligible positive samples observed in mid (DIM 60-240) and late (DIM 240-305) lactation. This study demonstrates that shedding of MAP into milk is affected by infection status of the cow as well as stage of lactation, providing useful information to producers to help break the cycle of infection within a herd. PMID:25064655

  18. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection.

    PubMed

    Li, Qingxue; Wilkie, Adrian R; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I

    2015-07-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  19. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection

    PubMed Central

    Li, Qingxue; Wilkie, Adrian R.; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I.

    2015-01-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  20. 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

    Jimenez-Coello, Matilde; Acosta-Viana, Karla Y; 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

  1. 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

  2. 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

    2016-01-01

    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

  3. 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

  4. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

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

    PubMed

    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

  6. 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

  7. The Ubiquitin-Proteasome System Plays an Important Role during Various Stages of the Coronavirus Infection Cycle ▿

    PubMed Central

    Raaben, Matthijs; Posthuma, Clara C.; Verheije, Monique H.; te Lintelo, Eddie G.; Kikkert, Marjolein; Drijfhout, Jan W.; Snijder, Eric J.; Rottier, Peter J. M.; de Haan, Cornelis A. M.

    2010-01-01

    The ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins. In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle. Inhibition of the proteasome by different chemical compounds (i.e., MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (i.e., mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV). MHV assembly and release were, however, not appreciably affected by these compounds. The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors. Stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2α. MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination. Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs. Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry. Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection. PMID:20484504

  8. First descriptions of early- and middle-stage copepodids of Anthosoma crassum (Dichelesthiidae: Siphonostomatoida) and lesions on shortfin makos (Isurus oxyrinchus) infected with A. crassum.

    PubMed

    Benz, George W; Borucinska, Joanna D; Greenwaldt, Scott A

    2002-02-01

    Early- and middle-stage copepodids of Anthosoma crassum (Dichelesthiidae: Siphonostomatoida) and lesions associated with A. crassum infections are described from samples collected from the jaws of shortfin makos captured off southern California. The copepodids did not possess frontal filaments or frontal organs, and they resided in a headstandlike position firmly attached by their embedded antennae. Copepod larvae and small adults were lodged in shallow mucosal ulcers that basally exhibited mild, acute granulocytic stomatitis; large adults were lodged in deep tunnels encompassing the anterior aspects of their bodies. Some lesions contained more than I copepod. Examinations of lesions revealed that A. crassum infection of shortfin makos can result in severe subacute, necrotizing stomatitis with hemorrhage, granulation tissue, and lymphocytic aggregations in the mucosa, and reactive lymphocytic infiltration of the submucosal skeletal muscle. Copepod gut contents consisted of shark erythrocytes, hemosiderin granules, and necrotic host cells. These observations, along with reports of sharks heavily infected with A. crassum, suggest that this copepod may sometimes play a role in the morbidity and mortality of sharks that it infects. PMID:12053965

  9. [Studies upon behaviour of snails in anthropogenically changed water environment. 1. Locomotor activity of Lymnaea stagnalis (L.), with regard to subpopulations infected with developmental stages of digeneans].

    PubMed

    Pokora, Zbigniew

    2002-01-01

    The aim of the paper was to analyse the locomotor activity of snails, Lymnaea stagnalis, with regard to physico-chemical properties of water in an inhabited reservoir and parasitic infection. The material was collected in selected anthropogenic water environments situated in the Upper Silesian Industrial Region (sinkhole ponds, sand- and clay-excavations). The locomotor activity of each snail was analysed in laboratory conditions by designation of number of penetrated segments, marked in tanks filled with water originating from a given reservoir, during 15', with intervals of 1'. It was observed the significant relationship between locomotor activity of examined snails and the water carbonaceous hardness (r = -0,812, at range of the independent variable 173.0-863.5 mg CaCO3/dm3). Correlation coefficients with other physico-chemical parameters of water were close to zero. Locomotion of snails infected with developmental stages of digenetic trematodes was significantly lower comparing to non-infected individuals. Locomotor activity of these former ones was dependend more on degree of the digestive gland damage by the parasite than on the infection agent. PMID:16883702

  10. 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

  11. 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

  12. NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria

    PubMed Central

    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.

    2014-01-01

    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. PMID:24379293

  13. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages. PMID:25573360

  14. The early stages of the immune response of the European abalone Haliotis tuberculata to a Vibrio harveyi infection.

    PubMed

    Cardinaud, Marion; Dheilly, Nolwenn M; Huchette, Sylvain; Moraga, Dario; Paillard, Christine

    2015-08-01

    Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone mortalities in France, Japan and Australia. In the European abalone, V. harveyi invades the circulatory system in a few hours after exposure and is lethal after 2 days of infection. In this study, we investigated the responses of European abalone immune cells over the first 24 h of infection. Results revealed an initial induction of immune gene expression including Rel/NF-kB, Mpeg and Clathrin. It is rapidly followed by a significant immuno-suppression characterized by reduced cellular hemocyte parameters, immune response gene expressions and enzymatic activities. Interestingly, Ferritin was overexpressed after 24 h of infection suggesting that abalone attempt to counter V. harveyi infection using soluble effectors. Immune function alteration was positively correlated with V. harveyi concentration. This study provides the evidence that V. harveyi has a hemolytic activity and an immuno-suppressive effect in the European abalone. PMID:25766281

  15. The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.

    PubMed

    Yau, Wai-Lok; Pescher, Pascale; MacDonald, Andrea; Hem, Sonia; Zander, Dorothea; Retzlaff, Silke; Blisnick, Thierry; Rotureau, Brice; Rosenqvist, Heidi; Wiese, Martin; Bastin, Philippe; Clos, Joachim; Späth, Gerald F

    2014-07-01

    During its life cycle, the protozoan pathogen Leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. Combining null mutant analysis with phosphorylation site-specific mutagenesis and functional complementation we genetically tested the requirement of the L. donovani chaperone cyclophilin 40 (LdCyP40) for infection. Targeted replacement of LdCyP40 had no effect on parasite viability, axenic amastigote differentiation, and resistance to various forms of environmental stress in culture, suggesting important functional redundancy to other parasite chaperones. However, ultrastructural analyses and video microscopy of cyp40-/- promastigotes uncovered important defects in cell shape, organization of the subpellicular tubulin network and motility at stationary growth phase. More importantly, cyp40-/- parasites were unable to establish intracellular infection in murine macrophages and were eliminated during the first 24 h post infection. Surprisingly, cyp40-/- infectivity was restored in complemented parasites expressing a CyP40 mutant of the unique S274 phosphorylation site. Together our data reveal non-redundant CyP40 functions in parasite cytoskeletal remodelling relevant for the development of infectious parasites in vitro independent of its phosphorylation status, and provide a framework for the genetic analysis of Leishmania-specific phosphorylation sites and their role in regulating parasite protein function. PMID:24811325

  16. 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...

  17. Role of lipids in the transmission of the infective stage (L3) of Strongylus vulgaris (Nematoda: Strongylida).

    PubMed

    Medica, D L; Sukhdeo, M V

    1997-10-01

    Infective larvae (L3) of Strongylus vulgaris have limited energy stores for host finding and for infection. For transmission to occur, the larvae must have sufficient energy to (a) migrate onto grass, where they are ingested by their equine host (host finding), and (b) penetrate into the host gut. This study is designed to test the hypothesis that L3 larvae of S. vulgaris partition their energy stores between locomotory activity (used in host finding) and infection activity (penetration). Chronic locomotory activity was stimulated by incubating S. vulgaris L3 larvae at a constant temperature (38 C). After 8 days of treatment, locomotory activity ceased (exhaustion). Exhausted L3 larvae had significantly decreased total lipid when compared to controls (P < 0.05), but there was no decrease in levels of protein of carbohydrate. Lipids of S. vulgaris L3 larvae are comprised of 9 fatty acids, some of which are depleted in exhausted worms (14:0, 14:1, 16:0, 16:1, 18:1, 18:2), whereas others (18:0, 20:4, 24:0) remain unchanged. These data suggest that specific fatty acids provide the energy source for locomotory activity in S. vulgaris. Exhausted L3 larvae were also less able to penetrate host cecal tissue in in vitro penetration assays when compared to controls (P < 0.05), suggesting that the depletion of individual fatty acids during locomotory activity also reduced infectivity. These data do not support the hypothesis that S. vulgaris L3 larvae partition their energy stores between host-finding and infection activities. A comparison of lipid storage profiles in the L3 larvae of 4 nematode species with similar transmission strategies (S. vulgaris, Strongylus edentatus, Strongylus equinus, and Haemonchus contortus) revealed similarities in the fatty acid composition of these species. These data suggest a relationship between transmission patterns and energy storage strategies in the L3 larvae of nematode parasites of vertebrates. PMID:9379277

  18. Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease.

    PubMed

    Ioannidis, Lisa J; Nie, Catherine Q; Ly, Ann; Ryg-Cornejo, Victoria; Chiu, Chris Y; Hansen, Diana S

    2016-02-01

    CXCL10, or IFN-γ-inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum-mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10(-/-) mice with bone marrow from either WT or CXCL10(-/-) mice. Similar to CXCL10(-/-) mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3(+)CD4(+) T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs. PMID:26718341

  19. Morphology of the infective larval stage of the equid parasite Habronema muscae (Spirurida: Habronematidae), from houseflies (Musca domestica).

    PubMed

    Buzzell, Gerald R; Tariq, Saeed; Traversa, Donato; Schuster, Rolf

    2011-03-01

    The infective larva of the spirurid nematode Habronema muscae, a parasite of houseflies, was measured and specimens fixed in Karnovsky's fluid were examined by scanning electron microscopy. The oral opening contains six teeth and is surrounded by large bilobed dorsal and ventral lips and smaller lateral lips. A pair of amphids lie behind the lateral lips. There are two rows of four cephalic papillae. The body is deeply ridged, both transversely and longitudinally. The caudal end of the worm is studded by small papillae. The position of the anal opening is somewhat ambiguous. These larval morphological features are discussed, as well as the changes which must have occurred in the metamorphosis of the infective larva to the adult in the stomach of horses. PMID:20949282

  20. Nervous Necrosis Virus Replicates Following the Embryo Development and Dual Infection with Iridovirus at Juvenile Stage in Grouper

    PubMed Central

    Hsu, Hao-Hsuan; Chen, Peng-Peng; Lee, Szu-Hsien; Chen, Young-Mao; Tsai, Tieh-Jung; Wang, Chien-Kai; Ku, Hsiao-Tung; Lee, Gwo-Bin; Chen, Tzong-Yueh

    2012-01-01

    Infection of virus (such as nodavirus and iridovirus) and bacteria (such as Vibrio anguillarum) in farmed grouper has been widely reported and caused large economic losses to Taiwanese fish aquaculture industry since 1979. The multiplex assay was used to detect dual viral infection and showed that only nervous necrosis virus (NNV) can be detected till the end of experiments (100% mortality) once it appeared. In addition, iridovirus can be detected in a certain period of rearing. The results of real-time PCR and in situ PCR indicated that NNV, in fact, was not on the surface of the eggs but present in the embryo, which can continue to replicate during the embryo development. The virus may be vertically transmitted by packing into eggs during egg development (formation) or delivering into eggs by sperm during fertilization. The ozone treatment of eggs may fail to remove the virus, so a new strategy to prevent NNV is needed. PMID:22563447

  1. Specific cessation of minus-strand RNA accumulation at an early stage of tobacco mosaic virus infection.

    PubMed

    Ishikawa, M; Meshi, T; Ohno, T; Okada, Y

    1991-02-01

    The time course of accumulation of viral plus-strand RNAs (genomic RNA and subgenomic mRNA for the coat protein) and minus-strand RNA in tobacco protoplasts synchronously infected with tobacco mosaic virus (TMV) RNA was examined. In protoplasts infected with the wild-type TMV L RNA, the plus and minus strands accumulated differently not only in quantity but also in the outline of kinetics. The time courses of accumulation of the genomic RNA and coat protein mRNA were similar: they became detectable at 2 or 4 h postinoculation (p.i.), and their accumulation increased until 14 to 18 h p.i. The accumulation rate reached the maximum at about 4 h p.i. and then gradually decreased. In contrast, accumulation of the minus-strand RNA ceased at 6 to 8 h p.i., at which time the plus-strand accumulation was already about 100 times greater and still continued vigorously. This specific halt of minus-strand accumulation was not caused exclusively by encapsidation of the genomic RNA, because a similar halt was observed upon infection with a deletion mutant that lacks the 30K and coat protein genes. Upon infection with a mutant that could not produce the 130K protein (one of the two proteins that are thought to be involved in viral RNA replication), the accumulation levels of both plus and minus strands were lower than that of the parental wild-type virus. Given these observations, possible mechanisms of TMV replication are discussed. PMID:1987377

  2. Growth of HIV-Infected Children in the Early Stage of Antiretroviral Treatment: A Retrospective Cohort Study in China.

    PubMed

    Hu, Ran; Mu, Weiwei; Sun, Xin; Wu, Hao; Pang, Lin; Wang, Liming; Zhao, Qingxia; Wu, Yasong; Zhao, Decai; Chen, Meiling; Ma, Ye; Zhang, Fujie

    2016-08-01

    Malnutrition and human immunodeficiency virus (HIV)-related complications are commonly seen in HIV-infected children, and these have been shown in high-prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled disease progression, whereas it effectively reverses underweight and growth retardation in HIV-infected children. This study was conducted to evaluate the growth status after initiation of ART in HIV-infected children in China. A retrospective cohort study was conducted based on the National Science and Technology Major Project. HIV-infected children who initiated antiretroviral treatment between January 1st, 2012 and December 31st, 2012 were followed up to December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro (plus). Linear mixed-effects models were used to model trajectories of weight- and height-for-age Z-scores. Seven hundred forty-four participants enrolled in the study, with 585 participants and 712 participants who had WAZ (weight-for-age Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After treatment, among the 125 underweight children, WAZ improved in 69 patients, regained more than -2 on average. Among the 301 stunted children, HAZ improved in 123 patients, regained more than -2 on average. WAZ improved for the first 6 months by 0.052 units each month and then stabilized, whereas HAZ consistently improved by 0.014 units each month over time. Antiretroviral treatment reversed the adverse effects of HIV to some degree. Early diagnosis and treatment, with an effective nutrition program, is necessary to improve malnutrition further. PMID:27509236

  3. ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection.

    PubMed

    Othumpangat, Sreekumar; Noti, John D; McMillen, Cynthia M; Beezhold, Donald H

    2016-01-01

    Intercellular cell adhesion molecule-1 (ICAM-1) is an inducible cell surface glycoprotein that is expressed on many cell types. Influenza virus infection enhanced ICAM-1 expression and messenger RNA levels. Human bronchial epithelial cells (HBEpC) and nasal epithelial cells, on exposure to different strains of influenza virus (H1N1, H3N2, and H9N1) showed significant increase in ICAM-1 gene expression (p<0.001) along with the ICAM-1 protein levels (surface and secreted). Depleting ICAM-1 in HBEpC with ICAM-1 siRNA and subsequently infecting with H1N1 showed increased viral copy numbers. Influenza virus infection in HBEpC resulted in up-regulation of NF-ĸB protein and the lack of ICAM-1 decreased NF-ĸB activity in NF-ĸB luciferase reporter assay. Addition of exogenous IL-1β to HBEpC induced the ICAM-1 expression and decreased matrix gene copy number. Taken together, HBEpC induced ICAM-1 plays a key role in modulating the influenza virus survival possibly through the NF-ĸB pathway. PMID:26499045

  4. [The effect of betain on biology and morphology of developmental stages of Eimeria acervulina in broiler chicks experimentally infected].

    PubMed

    Teixeira, Marcel; Niang, Tania Marcia S; Gomes, Augusto V da C; Lopes, Carlos Wilson G

    2006-01-01

    Purposing to investigate the betaine effect on biology and morphology of developmental stages of Eimeria acervulina, 420 broiler chicks Cobb were experimentally inoculated with 2 x 10(5) sporulated oocysts and housed in battery cages in a block design with five treatments and six replicates each, including a positive control, a group treated with salinomycin and growth promoter plus three levels of betaine as additive in the feed at 0.05, 0.10 and 0.15%. Measurements of oocysts, sporocysts and endogenous stages were performed as morphological parameters, while pre patent and patent periods and sporulation time were taken as biological parameters. Morphology was also associated with the mathematical constant Phi (1.618) to evaluate possible relationship. Betaine was able to cause modifications in both biology and morphology of oocysts and sporocysts, whereas it was weakly able to affect developmental stages based on trophozoites and macrogamonts measurements. According to the measures of sporocysts E. acervulina development was closely related to Phi. PMID:17196124

  5. Why the proportion of transmission during early-stage HIV infection does not predict the long-term impact of treatment on HIV incidence

    PubMed Central

    Hallett, Timothy B.

    2014-01-01

    Antiretroviral therapy (ART) reduces the infectiousness of HIV-infected persons, but only after testing, linkage to care, and successful viral suppression. Thus, a large proportion of HIV transmission during a period of high infectiousness in the first few months after infection (“early transmission”) is perceived as a threat to the impact of HIV “treatment-as-prevention” strategies. We created a mathematical model of a heterosexual HIV epidemic to investigate how the proportion of early transmission affects the impact of ART on reducing HIV incidence. The model includes stages of HIV infection, flexible sexual mixing, and changes in risk behavior over the epidemic. The model was calibrated to HIV prevalence data from South Africa using a Bayesian framework. Immediately after ART was introduced, more early transmission was associated with a smaller reduction in HIV incidence rate—consistent with the concern that a large amount of early transmission reduces the impact of treatment on incidence. However, the proportion of early transmission was not strongly related to the long-term reduction in incidence. This was because more early transmission resulted in a shorter generation time, in which case lower values for the basic reproductive number (R0) are consistent with observed epidemic growth, and R0 was negatively correlated with long-term intervention impact. The fraction of early transmission depends on biological factors, behavioral patterns, and epidemic stage and alone does not predict long-term intervention impacts. However, early transmission may be an important determinant in the outcome of short-term trials and evaluation of programs. PMID:25313068

  6. 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

  7. 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

    2016-01-01

    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. PMID:26983695

  8. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26983695

  10. 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.

  11. 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

  12. Correlation of Deoxynivalenol Accumulation in Fusarium-Infected Winter and Spring Wheat Cultivars with Secondary Metabolites at Different Growth Stages.

    PubMed

    Etzerodt, Thomas; Gislum, Rene; Laursen, Bente B; Heinrichson, Kirsten; Gregersen, Per L; Jørgensen, Lise N; Fomsgaard, Inge S

    2016-06-01

    Fusarium infection in wheat causes Fusarium head blight, resulting in yield losses and contamination of grains with trichothecenes. Some plant secondary metabolites inhibit accumulation of trichothecenes. Eighteen Fusarium infected wheat cultivars were harvested at five time points and analyzed for the trichothecene deoxynivalenol (DON) and 38 wheat secondary metabolites (benzoxazinoids, phenolic acids, carotenoids, and flavonoids). Multivariate analysis showed that harvest time strongly impacted the content of secondary metabolites, more distinctly for winter wheat than spring wheat. The benzoxazinoid 2-β-glucopyranoside-2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-glc), α-tocopherol, and the flavonoids homoorientin and orientin were identified as potential inhibitors of DON accumulation. Several phenolic acids, lutein and β-carotene also affected DON accumulation, but the effect varied for the two wheat types. The results could form a basis for choosing wheat cultivars using metabolite profiling as a marker for selecting wheat cultivars with improved resistance against Fusarium head blight and accumulation of trichothecene toxins in wheat heads. PMID:27195655

  13. Stress-Induced Glucocorticoids at the Earliest Stages of Herpes Simplex Virus-1 Infection Suppress Subsequent Antiviral Immunity, Implicating Impaired Dendritic Cell Function

    PubMed Central

    Elftman, Michael D.; Hunzeker, John T.; Mellinger, Jennifer C.; Bonneau, Robert H.; Norbury, Christopher C.; Truckenmiller, Mary E.

    2013-01-01

    The systemic elevation of psychological stress-induced glucocorticoids strongly suppresses CD8+ T cell immune responses resulting in diminished antiviral immunity. However, the specific cellular targets of stress/glucocorticoids, the timing of exposure, the chronology of immunological events, and the underlying mechanisms of this impairment are incompletely understood. In this study, we address each of these questions in the context of a murine cutaneous HSV infection. We show that exposure to stress or corticosterone in only the earliest stages of an HSV-1 infection is sufficient to suppress, in a glucocorticoid receptor-dependent manner, the subsequent antiviral immune response after stress/corticosterone has been terminated. This suppression resulted in early onset and delayed resolution of herpetic lesions, reduced viral clearance at the site of infection and draining popliteal lymph nodes (PLNs), and impaired functions of HSV-specific CD8+ T cells in PLNs, including granzyme B and IFN-γ production and the ability to degranulate. In knockout mice lacking glucocorticoid receptors only in T cells, we show that these impaired CD8+ T cell functions are not due to direct effects of stress/corticosterone on the T cells, but the ability of PLN-derivcd dendritic cells to prime HSV-1–specific CD8+ T cells is functionally impaired. These findings highlight the susceptibility of critical early events in the generation of an antiviral immune response to neuroendocrine modulation and implicate dendritic cells as targets of stress/glucocorticoids in vivo. These findings also provide insight into the mechanisms by which the clinical use of glucocorticoids contributes to altered immune responses in patients with viral infections or tumors. PMID:20089700

  14. 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

  15. Role of the long cytoplasmic domain of the SIV Env glycoprotein in early and late stages of infection

    PubMed Central

    Vzorov, Andrei N; Weidmann, Armin; Kozyr, Natalia L; Khaoustov, Vladimir; Yoffe, Boris; Compans, Richard W

    2007-01-01

    Background The Env glycoproteins of retroviruses play an important role in the initial steps of infection involving the binding to cell surface receptors and entry by membrane fusion. The Env glycoprotein also plays an important role in viral assembly at a late step of infection. Although the Env glycoprotein interacts with viral matrix proteins and cellular proteins associated with lipid rafts, its possible role during the early replication events remains unclear. Truncation of the cytoplasmic tail (CT) of the Env glycoprotein is acquired by SIV in the course of adaptation to human cells, and is known to be a determinant of SIV pathogenicity. Results We compared SIV viruses with full length or truncated (T) Env glycoproteins to analyze possible differences in entry and post-entry events, and assembly of virions. We observed that early steps in replication of SIV with full length or T Env were similar in dividing and non-dividing cells. However, the proviral DNA of the pathogenic virus clone SIVmac239 with full length Env was imported to the nucleus about 20-fold more efficiently than proviral DNA of SIVmac239T with T Env, and 100-fold more efficiently than an SIVmac18T variant with a single mutation A239T in the SU subunit and with a truncated cytoplasmic tail (CT). In contrast, proviral DNA of SIVmac18 with a full length CT and with a single mutation A239T in the SU subunit was imported to the nucleus about 50-fold more efficiently than SIVmac18T. SIV particles with full length Env were released from rhesus monkey PBMC, whereas a restriction of release of virus particles was observed from human 293T, CEMx174, HUT78 or macrophages. In contrast, SIV with T Envs were able to overcome the inhibition of release in human HUT78, CEMx174, 293T or growth-arrested CEMx174 cells and macrophages resulting in production of infectious particles. We found that the long CT of the Env glycoprotein was required for association of Env with lipid rafts. An Env mutant C787S which

  16. Ultrastructural changes in the third-stage, infective larvae of ruminant nematodes treated with sainfoin (Onobrychis viciifolia) extract.

    PubMed

    Brunet, S; Fourquaux, I; Hoste, H

    2011-12-01

    Plants rich in condensed tannins are an alternative to chemical anthelmintics to control gastrointestinal nematodes (GINs) in ruminants. Previous functional studies have shown that sainfoin extracts affect the two forms of infective larvae (L3), ensheathed and exsheathed. However, the mechanisms of action remain unknown. The aim of this study was thus to compare ultrastructural changes in ensheathed and exsheathed L3 of two GIN species after in vitro contact with sainfoin extracts using transmission electron microscopy. The main changes identified were an alteration of the hypodermis, the presence of numerous vesicles in the cytoplasm and degeneration and/or death of muscular and intestinal cells. The changes suggested similar and nonspecies-specific lesions in the two nematode species. Comparison of the modifications found in the ensheathed vs. exsheathed L3s revealed different locations of the main cellular changes depending on the larval form. It is hypothesized that these spatial differences in lesions are mainly influenced by the presence of the sheath which favors contact between the active compounds and either the cuticle or the digestive tract. Overall, our observations suggest that the functional changes observed in the biology of GIN L3s after contact with sainfoin extracts are mediated through a direct mode of action, i.e. different interactions between the bioactive plant metabolites and the nematode structure depending on the route of contact. PMID:21787880

  17. Evidence of Blood Stage Efficacy with a Virosomal Malaria Vaccine in a Phase IIa Clinical Trial

    PubMed Central

    Thompson, Fiona M.; Porter, David W.; Okitsu, Shinji L.; Westerfeld, Nicole; Vogel, Denise; Todryk, Stephen; Poulton, Ian; Correa, Simon; Hutchings, Claire; Berthoud, Tamara; Dunachie, Susanna; Andrews, Laura; Williams, Jack L.; Sinden, Robert; Gilbert, Sarah C.; Pluschke, Gerd; Zurbriggen, Rinaldo; Hill, Adrian V. S.

    2008-01-01

    Background Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle. Methods This was a Phase I/IIa study of a new combination malaria vaccine FFM ME-TRAP+PEV3A. PEV3A includes peptides from both the pre-erythrocytic circumsporozoite protein and the blood-stage antigen AMA-1. This study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. The participants were healthy, malaria naïve volunteers, from Oxford. The interventions were vaccination with PEV3A alone, or PEV3A+FFM ME-TRAP. The main outcome measure was protection from malaria in a sporozoite challenge model. Other outcomes included measures of parasite specific immune responses induced by either vaccine; and safety, assessed by collection of adverse event data. Results We observed evidence of blood stage immunity in PEV3A vaccinated volunteers, but no volunteers were completely protected from malaria. PEV3A induced high antibody titres, and antibodies bound parasites in immunofluorescence assays. Moreover, we observed boosting of the vaccine-induced immune response by sporozoite challenge. Immune responses induced by FFM ME-TRAP were unexpectedly low. The vaccines were safe, with comparable side effect profiles to previous trials. Although there was no sterile protection two major observations support an effect of the vaccine-induced response on blood stage parasites: (i) Lower rates of parasite growth were observed in volunteers vaccinated with PEV3A compared to unvaccinated controls (p = 0.012), and this was reflected in the PCR results from PEV3A vaccinated volunteers. These showed early control of parasitaemia by some volunteers in this

  18. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxaemia

    PubMed Central

    Cote, C. K.; Kaatz, L.; Reinhardt, J.; Bozue, J.; Tobery, S. A.; Bassett, A. D.; Sanz, P.; Darnell, S. C.; Alem, F.; O’Brien, A. D.

    2012-01-01

    Current vaccine approaches to combat anthrax are effective; however, they target only a single protein [the protective antigen (PA) toxin component] that is produced after spore germination. PA production is subsequently increased during later vegetative cell proliferation. Accordingly, several aspects of the vaccine strategy could be improved. The inclusion of spore-specific antigens with PA could potentially induce protection to initial stages of the disease. Moreover, adding other epitopes to the current vaccine strategy will decrease the likelihood of encountering a strain of Bacillus anthracis (emerging or engineered) that is refractory to the vaccine. Adding recombinant spore-surface antigens (e.g. BclA, ExsFA/BxpB and p5303) to PA has been shown to augment protection afforded by the latter using a challenge model employing immunosuppressed mice challenged with spores derived from the attenuated Sterne strain of B. anthracis. This report demonstrated similar augmentation utilizing guinea pigs or mice challenged with spores of the fully virulent Ames strain or a non-toxigenic but encapsulated ΔAmes strain of B. anthracis, respectively. Additionally, it was shown that immune interference did not occur if optimal amounts of antigen were administered. By administering the toxin and spore-based immunogens simultaneously, a significant adjuvant effect was also observed in some cases. Thus, these data further support the inclusion of recombinant spore antigens in next-generation anthrax vaccine strategies. PMID:22767539

  19. trans-dominant interference with virus infection at two different stages by a mutant envelope protein of Friend murine leukemia virus.

    PubMed Central

    Matano, T; Odawara, T; Ohshima, M; Yoshikura, H; Iwamoto, A

    1993-01-01

    A dominant negative mutant Friend murine leukemia virus (FMLV) env gene was cloned from an immunoselected Friend erythroleukemia cell. The mutant env had a point mutation which resulted in a Cys-to-Arg substitution at the 361st amino acid in the FMLV envelope protein (Env). The mutant Env was retained in the endoplasmic reticulum (ER) and accumulated because of its slow degradation. The NIH 3T3 cells expressing the mutant env were resistant to ecotropic Moloney MLV (MoMLV) penetration, suggesting that the mutant Env traps the ecotropic MLV receptors in the ER. When the mutant env gene was transfected into and expressed in the cells persistently infected with MoMLV, the wild-type Env was trapped in the ER, and the MoMLV production was suppressed. Thus, the mutant Env accumulating in the ER trans-dominantly and efficiently interfered with the ecotropic MLV infection at both the early and the late stages. Images PMID:8445721

  20. Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy.

    PubMed

    Fortier, Marie-Eve; Luheshi, Giamal N; Boksa, Patricia

    2007-08-01

    Maternal infection during pregnancy is a risk factor for some psychiatric illnesses of neurodevelopmental origin such as schizophrenia and autism. In experimental animals, behavioral and neuropathological outcomes relevant to schizophrenia have been observed in offspring of infected dams. However, the type of infectious agent used and gestational age at time of administration have varied. The objective of the present study was to compare the effects of prenatal challenge with different immune agents given at different time windows during gestation on behavioral outcomes in offspring. For this, pregnant rats were administered bacterial endotoxin (lipopolysaccharide, LPS), the viral mimic polyinosinic: polycytidylic acid (poly I:C), or turpentine, an inducer of local inflammation, at doses known to produce fever, at three different stages in pregnancy: embryonic day (E)10-11, E15-16 and E18-19. Prepulse inhibition of acoustic startle (PPI) was later measured in male adult offspring. PPI was significantly decreased in offspring after prenatal LPS treatment at E15-16 and E18-19. Intramuscular injection of pregnant dams with turpentine at E15-16 also decreased PPI in adult offspring. Maternal poly I:C administration had no significant effect on PPI in offspring. In contrast to prenatal LPS exposure, acute LPS administration to naive adult males had no effect on PPI. Thus, prenatal exposure both to a systemic immunogen and to local inflammation at brief periods during later pregnancy produced lasting deficits in PPI in rat offspring. These findings support the idea that maternal infection during critical windows of pregnancy could contribute to sensorimotor gating deficits in schizophrenia. PMID:17553574

  1. 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

  2. Comparative proteomic analysis reveals that T3SS, Tfp, and xanthan gum are key factors in initial stages of Citrus sinensis infection by Xanthomonas citri subsp. citri.

    PubMed

    Facincani, Agda P; Moreira, Leandro M; Soares, Márcia R; Ferreira, Cristiano B; Ferreira, Rafael M; Ferro, Maria I T; Ferro, Jesus A; Gozzo, Fabio C; de Oliveira, Julio C F

    2014-03-01

    The bacteria Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus canker. The disease symptoms are characterized by localized host cell hyperplasia followed by tissue necrosis at the infected area. An arsenal of bacterial pathogenicity- and virulence-related proteins is expressed to ensure a successful infection process. At the post-genomic stage of Xac, we used a proteomic approach to analyze the proteins that are displayed differentially over time when the pathogen attacks the host plant. Protein extracts were prepared from infectious Xac grown in inducing medium (XAM1) for 24 h or from host citrus plants for 3 or 5 days after infection, detached times to evaluate the adaptation and virulence of the pathogen. The protein extracts were proteolyzed, and the peptides derived from tryptic digestion were investigated using liquid chromatography and tandem mass spectrometry. Changes in the protein expression profile were compared with the Xac genome and the proteome recently described under non-infectious conditions. An analysis of the proteome of Xac under infectious conditions revealed proteins directly involved in virulence such as the type III secretion system (T3SS) and effector proteins (T3SS-e), the type IV pilus (Tfp), and xanthan gum biosynthesis. Moreover, four new mutants related to proteins detected in the proteome and with different functions exhibited reduced virulence relative to the wild-type proteins. The results of the proteome analysis of infectious Xac define the processes of adaptation to the host and demonstrate the induction of the virulence factors of Xac involved in plant-pathogen interactions. PMID:24676796

  3. Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up

    PubMed Central

    Esser, Stefan; Eisele, Lewin; Schwarz, Birte; Schulze, Christina; Holzendorf, Volker; Brockmeyer, Nobert H; Hower, Martin; Kwirant, Friedhelm; Rudolph, Roland; Neumann, Till; Reinsch, Nico

    2014-01-01

    Introduction Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. Methods The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. Results 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88–0.94]) and ART (per y: HR: 0.81 [0.79–0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8–482.8) versus 574 cells/µL (IQR: 406–786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies

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

    PubMed Central

    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. PMID:25408684

  5. 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. PMID:25408684

  6. 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

  7. A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

    PubMed Central

    Douglas, Alexander D.; Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Crosnier, Cécile; Bartholdson, S. Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E.; Ventocilla, Julio A.; Leiva, Karina P.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G.W.; Turner, Alison V.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Wu, Yimin; Long, Carole A.; Wright, Gavin J.; Lescano, Andrés G.; Draper, Simon J.

    2015-01-01

    Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. PMID:25590760

  8. Respiratory viral infections in institutions from late stage of the first and second waves of pandemic influenza A (H1N1) 2009, Ontario, Canada

    PubMed Central

    Asner, Sandra; Peci, Adriana; Marchand‐Austin, Alex; Winter, Anne‐Luise; Olsha, Romy; Kristjanson, Erik; Low, Donald E.; Gubbay, Jonathan B.

    2012-01-01

    Please cite this paper as: Asner et al. (2012) Respiratory viral infections in institutions from late stage of the first and second waves of pandemic A (H1N1) 2009, Ontario, Canada. Influenza and Other Respiratory Viruses 6(3), e11–e15. We report the impact of respiratory viruses on various outbreak settings by using surveillance data from the late first and second wave periods of the 2009 pandemic. A total of 278/345(78·5%) outbreaks tested positive for at least one respiratory virus by multiplex PCR. We detected A(H1N1)pdm09 in 20·6% of all reported outbreaks of which 54·9% were reported by camps, schools, and day cares (CSDs) and 29·6% by long‐term care facilities (LCFTs), whereas enterovirus/human rhinovirus (ENT/HRV) accounted for 62% outbreaks of which 83·7% were reported by long‐term care facilities (LCTFs). ENT/HRV was frequently identified in LTCF outbreaks involving elderly residents, whereas in CSDs, A(H1N1)pdm09 was primarily detected. PMID:22353417

  9. Characterization and cloning of metallo-proteinase in the excretory/secretory products of the infective-stage larva of Trichinella spiralis.

    PubMed

    Lun, H M; Mak, C H; Ko, R C

    2003-05-01

    Inhibitor sensitivity assays using azocaesin and FTC-caesin as substrates showed that the excretory/secretory (E/S) products of the infective-stage larvae of Trichinella spiralis contained serine, metallo-, cysteine and aspartic proteinases. The activity of the metallo-proteinase was zinc ion dependent (within a range of ZnSO(4) concentrations). Gelatin-substrate gel electrophoresis revealed two bands of molecular mass 48 and 58 kDa which were sensitive to the metallo-proteinase inhibitor EDTA. The former peptide was probably a cleavage product of the latter. The authenticity of the 58 kDa metallo-proteinase as an E/S product was confirmed by immunoprecipitation. Using PCR and RACE reactions, a complete nucleotide sequence of the metallo-proteinase gene was obtained. It comprised 2,223 bp with an open reading frame encoding 604 amino acid residues. The 3' untranslated region consisted of 352 bp, including a polyadenylation signal AATAA. A consensus catalytic zinc-binding motif was present. The conserved domains suggest that the cloned metallo-proteinase belongs to the astacin family and occurs as a single copy gene with 11 introns and 10 exons. Cluster analysis showed that the sequence of the metallo-proteinase gene of T. spiralis resembles those of Caenorhabdites elegans and Strongyloides stercoralis. PMID:12743801

  10. Overview of the functional virulent genome of the coffee leaf rust pathogen Hemileia vastatrix with an emphasis on early stages of infection

    PubMed Central

    Talhinhas, Pedro; Azinheira, Helena G.; Vieira, Bruno; Loureiro, Andreia; Tavares, Sílvia; Batista, Dora; Morin, Emmanuelle; Petitot, Anne-Sophie; Paulo, Octávio S.; Poulain, Julie; Da Silva, Corinne; Duplessis, Sébastien; Silva, Maria do Céu; Fernandez, Diana

    2014-01-01

    Hemileia vastatrix is the causal agent of coffee leaf rust, the most important disease of coffee Arabica. In this work, a 454-pyrosequencing transcriptome analysis of H. vastatrix germinating urediniospores (gU) and appressoria (Ap) was performed and compared to previously published in planta haustoria-rich (H) data. A total of 9234 transcripts were identified and annotated. Ca. 50% of these transcripts showed no significant homology to international databases. Only 784 sequences were shared by the three conditions, and 75% were exclusive of either gU (2146), Ap (1479) or H (3270). Relative transcript abundance and RT-qPCR analyses for a selection of genes indicated a particularly active metabolism, translational activity and production of new structures in the appressoria and intense signaling, transport, secretory activity and cellular multiplication in the germinating urediniospores, suggesting the onset of a plant-fungus dialogue as early as at the germ tube stage. Gene expression related to the production of carbohydrate-active enzymes and accumulation of glycerol in germinating urediniospores and appressoria suggests that combined lytic and physical mechanisms are involved in appressoria-mediated penetration. Besides contributing to the characterization of molecular processes leading to appressoria-mediated infection by rust fungi, these results point toward the identification of new H. vastatrix candidate virulence factors, with 516 genes predicted to encode secreted proteins. PMID:24672531

  11. 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

  12. 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

    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

  13. 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

  14. Assessment of Immune Interference, Antagonism and Diversion following Human Immunization with Bi-Allelic Blood-Stage Malaria Viral Vectored Vaccines and Controlled Malaria Infection

    PubMed Central

    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.

    2012-01-01

    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 antigen variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). However previous studies, utilizing malaria antigens, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands (APL), in such a vaccine may be detrimental to both the priming and in vivo re-stimulation of antigen-experienced T cells. Here we analyze the T cell responses to two alleles of MSP1 and AMA1 induced by vaccination of malaria-naïve adult volunteers with bi-valent viral vectored vaccine candidates. We show a significant bias to the 3D7/MAD20 allele compared to the Wellcome allele for the 33kDa region of MSP1, but not for the 19kDa fragment or the AMA1 antigen. Whilst this bias could be caused by ‘immune interference’ at priming, the data don’t support a significant role for ‘immune antagonism’ during memory T cell re-stimulation, 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 towards the Wellcome allele. PMID:23293353

  15. Limited Interference at the Early Stage of Infection between Two Recombinant Novirhabdoviruses: Viral Hemorrhagic Septicemia Virus and Infectious Hematopoietic Necrosis Virus▿ †

    PubMed Central

    Biacchesi, Stéphane; Lamoureux, Annie; Mérour, Emilie; Bernard, Julie; Brémont, Michel

    2010-01-01

    The genome sequence of a hypervirulent novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) French strain 23-75, was determined. Compared to the genome of the prototype Fil3 strain, a number of substitutions, deletions, and insertions were observed. Following the establishment of a plasmid-based minigenome replication assay, recombinant VHSV (rVHSV) was successfully recovered. rVHSV exhibits wild-type-like growth properties in vitro as well as in vivo in rainbow trout. The dispensable role of NV for the novirhabdovirus replication was confirmed by generating rVHSV-ΔNV, in which the NV gene was deleted. This deletion mutant was shown to be as debilitated as that previously described for infectious hematopoietic necrosis virus (IHNV), a distantly related novirhabdovirus (S. Biacchesi, M. I. Thoulouze, M. Bearzotti, Y. X. Yu, and M. Bremont, J. Virol. 74:11247-11253, 2000). Recombinant VHSV and IHNV expressing tdTomato and GFPmax reporter genes, respectively, were generated, demonstrating the potential of these rhabdoviruses to serve as viral vectors. Interestingly, rIHNV-GFPmax could be recovered using the replicative complex proteins of either virus, whereas rVHSV-Tomato could be recovered only by using its own replicative complex, reflecting that the genome signal sequences of VHSV are relatively distant from those of IHNV and do not allow their cross-recognition. Moreover, the use of heterologous protein combinations underlined the importance of strong protein-protein interactions for the formation of a functional ribonucleoprotein complex. The rIHNV-GFPmax and rVHSV-Tomato viruses were used to simultaneously coinfect cell monolayers. It was observed that up to 74% of the cell monolayer was coinfected by both viruses, demonstrating that a limited interference phenomenon exists during the early stage of primary infection, and it was not mediated by a cellular antiviral protein or by some of the viral proteins. PMID:20631140

  16. Factors associated with initiation of antiretroviral therapy in the advanced stages of HIV infection in six Ethiopian HIV clinics, 2012 to 2013

    PubMed Central

    Nash, Denis; Tymejczyk, Olga; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Yigzaw, Muluneh; Elul, Batya; Remien, Robert H; Lahuerta, Maria; Daba, Shalo; El Sadr, Wafaa; Melaku, Zenebe

    2016-01-01

    Introduction Most HIV-positive persons in sub-Saharan Africa initiate antiretroviral therapy (ART) with advanced infection (late ART initiation). Intervening on the drivers of late ART initiation is a critical step towards achieving the full potential of HIV treatment scale-up. This study aimed to identify modifiable factors associated with late ART initiation in Ethiopia. Methods From 2012 to 2013, Ethiopian adults (n=1180) were interviewed within two weeks of ART initiation. Interview data were merged with HIV care histories to assess correlates of late ART initiation (CD4+ count <150 cells/µL or World Health Organization Stage IV). Results The median CD4 count at enrolment in HIV care was 263 cells/µL (interquartile range (IQR): 140 to 390) and 212 cells/µL (IQR: 119 to 288) at ART initiation. Overall, 31.2% of participants initiated ART late, of whom 85.1% already had advanced HIV disease at enrolment. Factors associated with higher odds of late ART initiation included male sex (vs. non-pregnant females; adjusted odds ratio (aOR): 2.02; 95% CI: 1.50 to 2.73), high levels of psychological distress (vs. low/none, aOR: 1.96; 95% CI: 1.34 to 2.87), perceived communication barriers with providers (aOR: 2.42, 95% CI: 1.24 to 4.75), diagnosis via provider initiated testing (vs. voluntary counselling and testing, aOR: 1.47, 95% CI: 1.07 to 2.04), tuberculosis (TB) treatment prior to ART initiation (aOR: 2.16, 95% CI: 1.43 to 3.25) and a gap in care of six months or more prior to ART initiation (aOR: 2.02, 95% CI: 1.10 to 3.72). Testing because of partner illness/death (aOR: 0.64, 95% CI: 0.42 to 0.95) was associated with lower odds of late ART initiation. Conclusions Programmatic initiatives promoting earlier diagnosis, engagement in pre-ART care, and integration of TB and HIV treatments may facilitate earlier ART initiation. Men and those experiencing psychological distress may also benefit from targeted support prior to ART initiation. PMID:27113335

  17. Leishmania (Viannia) braziliensis amastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection.

    PubMed

    Gomes, Clayson M; Ávila, Lucilla R; Santos, Jéssica C; Oliveira, Pollyana G; Tomé, Fernanda D; Pereira, Ledice I A; Dorta, Miriam L; Lino, Ruy S; Ribeiro-Dias, Fátima; Oliveira, Milton A P

    2016-06-01

    Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate. PMID:27073255

  18. Targeting of a Fixed Bacterial Immunogen to Fc Receptors Reverses the Anti-Inflammatory Properties of the Gram-Negative Bacterium, Francisella tularensis, during the Early Stages of Infection.

    PubMed

    Babadjanova, Zulfia; Wiedinger, Kari; Gosselin, Edmund J; Bitsaktsis, Constantine

    2015-01-01

    Production of pro-inflammatory cytokines by innate immune cells at the early stages of bacterial infection is important for host protection against the pathogen. Many intracellular bacteria, including Francisella tularensis, the agent of tularemia, utilize the anti-inflammatory cytokine IL-10, to evade the host immune response. It is well established that IL-10 has the ability to inhibit robust antigen presentation by dendritic cells and macrophages, thus suppressing the generation of protective immunity. The pathogenesis of F. tularensis is not fully understood, and research has failed to develop an effective vaccine to this date. In the current study, we hypothesized that F. tularensis polarizes antigen presenting cells during the early stages of infection towards an anti-inflammatory status characterized by increased synthesis of IL-10 and decreased production of IL-12p70 and TNF-α in an IFN-ɣ-dependent fashion. In addition, F. tularensis drives an alternative activation of alveolar macrophages within the first 48 hours post-infection, thus allowing the bacterium to avoid protective immunity. Furthermore, we demonstrate that targeting inactivated F. tularensis (iFt) to Fcγ receptors (FcɣRs) via intranasal immunization with mAb-iFt complexes, a proven vaccine strategy in our laboratories, reverses the anti-inflammatory effects of the bacterium on macrophages by down-regulating production of IL-10. More specifically, we observed that targeting of iFt to FcγRs enhances the classical activation of macrophages not only within the respiratory mucosa, but also systemically, at the early stages of infection. These results provide important insight for further understanding the protective immune mechanisms generated when targeting immunogens to Fc receptors. PMID:26114641

  19. 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. PMID:19654061

  20. The critical time of avian leukosis virus subgroup J-mediated immunosuppression during early stage infection in specific pathogen-free chickens.

    PubMed

    Wang, Feng; Wang, Xiaowei; Chen, Hongbo; Liu, Jianzhu; Cheng, Ziqiang

    2011-09-01

    The critical time of avian leukosis virus subgroup J (ALV-J)-mediated immunosuppression was determined by body weight, relative immune organ weight, histopathology, and presence of group specific antigen and antibodies in specific pathogen-free (SPF) chickens. CD4(+) and CD8(+) cell activity in the spleen, total and differential leukocyte counts in blood, and viral RNA levels in spleen were measured. Significant growth suppression was observed in the two ALV-J-infected groups. A strong immune response by infected groups was present in spleen at 2-weeks-of-age, but after 4-weeks-of-age, the response decreased quickly. The thymus and bursa showed persistent immunosuppression until 4-weeks-of-age. Proliferation of fibroblasts and dendritic cells were observed in immune organs at 4- and 5-weeks-of-age. However, the granulocyte cell number was markedly lower in the infected groups than in the control group. In group 1 (day 1 infection) CD4(+) cells increased during the second week but significantly decreased during the fourth week, while group 2 (day 7 infection) showed the opposite effect. Viral RNA increased significantly by the fourth week. These data identify 3~4 weeks post-infection as the key time at which the ALV-J virus exerts its immunosuppressive effects on the host. PMID:21897096

  1. The critical time of avian leukosis virus subgroup J-mediated immunosuppression during early stage infection in specific pathogen-free chickens

    PubMed Central

    Wang, Feng; Wang, Xiaowei; Chen, Hongbo; Liu, Jianzhu

    2011-01-01

    The critical time of avian leukosis virus subgroup J (ALV-J)-mediated immunosuppression was determined by body weight, relative immune organ weight, histopathology, and presence of group specific antigen and antibodies in specific pathogen-free (SPF) chickens. CD4+ and CD8+ cell activity in the spleen, total and differential leukocyte counts in blood, and viral RNA levels in spleen were measured. Significant growth suppression was observed in the two ALV-J-infected groups. A strong immune response by infected groups was present in spleen at 2-weeks-of-age, but after 4-weeks-of-age, the response decreased quickly. The thymus and bursa showed persistent immunosuppression until 4-weeks-of-age. Proliferation of fibroblasts and dendritic cells were observed in immune organs at 4- and 5-weeks-of-age. However, the granulocyte cell number was markedly lower in the infected groups than in the control group. In group 1 (day 1 infection) CD4+ cells increased during the second week but significantly decreased during the fourth week, while group 2 (day 7 infection) showed the opposite effect. Viral RNA increased significantly by the fourth week. These data identify 3~4 weeks post-infection as the key time at which the ALV-J virus exerts its immunosuppressive effects on the host. PMID:21897096

  2. Parasite-specific IgM plays a significant role in the protective immune response to asexual erythrocytic stage Plasmodium chabaudi AS infection.

    PubMed

    Couper, K N; Phillips, R S; Brombacher, F; Alexander, J

    2005-05-01

    A comparison of Plasmodium chabaudi AS infection in BALB/c and BALB/c IgM-deficient mice demonstrated a protective role for IgM during infection. IgM-/- mice, unlike microMT mice, display competent B cell humoral immune responses. Increased susceptibility of IgM-/- mice was demonstrated by increased mortality, an advanced ascending infection and higher peak parasitaemia, as well as enhanced anaemia and weight loss compared with wild-type mice. The recrudescent parasitaemias were also higher in the IgM-/- mice. Early specific IgM production in P. chabaudi-infected wild-type mice was followed by IgG1 and IgG2a production, while IgG1 and IgG2a production in IgM-/- mice was preceded by specific IgD production. No protective role for natural IgM against P. chabaudi AS infection was detected as passive transfer of naïve WT serum into IgM-/- mice did not alter the disease outcome or reduce parasite numbers. Passive transfer of WT antiserum, containing predominantly specific IgM, into IgM-/- mice delayed the ascending parasitaemia and reduced mortality. Similarly, coating parasitized red blood cells with WT antiserum, but not IgM-/- antisera, prior to infection also slightly delayed the ascending acute parasitaemia. Specific IgM therefore plays an important role in the limitation of parasite replication during asexual erythrocytic P. chabaudi AS infection. PMID:15987340

  3. Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice.

    PubMed

    Wu, Xilin; Liu, Li; Cheung, Ka-Wai; Wang, Hui; Lu, Xiaofan; Cheung, Allen Ka Loon; Liu, Wan; Huang, Xiuyan; Li, Yanlei; Chen, Zhiwei W; Chen, Samantha M Y; Zhang, Tong; Wu, Hao; Chen, Zhiwei

    2016-09-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. PMID:26838362

  4. 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. PMID:22584045

  5. Impeded establishment of the infective stage of Trichinella in the intestinal mucosa of mice by passive transfer of an IgA monoclonal antibody.

    PubMed

    Inaba, Takashi; Sato, Hiroshi; Kamiya, Haruo

    2003-11-01

    Our previous study showed that the IgA monoclonal antibody (mAb) HUSM-Tb1 forms immunoprecipitates on the cuticular surface of infective larvae of Trichinella britovi, and that intraperitoneal injection of this mAb to mice 5 hr before challenge infection confers a high level of protection against intestinal T. britovi. The same treatment produced a similar effect in BALB/c mice inoculated orally with Trichinella pseudospiralis larvae, indicating that the effects may be seen upon most members of the genus Trichinella. Worms recovered from the intestinal mucosa at 1 hr after challenge infection with T. pseudospiralis was few in mice passively immunized with the mAb, whereas a substantial number of worms were recovered from the mucosa of control groups. These results suggest that the IgA mAb impedes establishment of infective Trichinella worms in the intestinal mucosa. Trichinella worms inoculated orally into BALB/c mice vaccinated with ultraviolet-irradiated muscle larvae 3 weeks earlier were expelled between days 4 and 7 after challenge infection. Although the mAb HUSM-Tb1 originated from the mesenteric lymph node cells of mice vaccinated repeatedly with such irradiated larvae, IgA-mediated expulsion does not seem to play an important role in this vaccination model. PMID:14665753

  6. Thai koi-hoi snail dish and angiostrongyliasis due to Angiostrongylus cantonensis: Effects of food flavoring and alcoholic drink on the third-stage larvae in infected snail meat.

    PubMed

    Eamsobhana, Praphathip; Yoolek, Adisak; Punthuprapasa, Paibulaya; Yong, Hoi-Sen

    2009-04-01

    Human infection with the rat lungworm Angiostrongylus cantonensis (Parastrongylus cantonensis) in Thailand, especially in the northeastern region, is associated with the habit of eating koi-hoi, which contains raw snail meat. Infection results from the snails being carriers of the larval parasite. The present study was conducted to assess the effect of food flavorings in koi-hoi, alcohol, and exposure time of the two variable on the infective larvae of A. cantonensis. Infected Biomphalaria glabrata snails were used for koi-hoi preparation. Raw snail meat was mixed with koi-hoi flavoring and left at room temperature for various time periods ranging from 5 to 60 minutes. At a predetermined time, two pieces of snail meat were removed at random and examined for viability (as determined by motility) of the parasitic third-stage larvae. At the same time, two random pieces of snail meat were removed and treated with 10 mL of a local 40% alcoholic drink for 30 minutes before examination of larval viability. Exposure of infected snail meat for 10 minutes or more to koi-hoi food flavoring resulted in significantly more nonmotile (dying or dead) larvae. Addition of the local alcoholic drink after exposure to the flavoring exerted an additional killing effect on the larvae. Despite long exposure time, both the koi-hoi flavoring and addition of alcoholic drink were not completely effective in killing the infective larvae in the snail meat. Thorough cooking of the food intended for human consumption should still be practiced. PMID:19272010

  7. Disseminated Mycobacterium abscessus Complex Infection Manifesting as Multiple Areas of Lymphadenitis and Skin Abscess in the Preclinical Stage of Acute Lymphocytic Leukemia.

    PubMed

    Tahara, Masahiro; Yatera, Kazuhiro; Yamasaki, Kei; Orihashi, Takeshi; Hirosawa, Makoto; Ogoshi, Takaaki; Noguchi, Shingo; Nishida, Chinatsu; Ishimoto, Hiroshi; Yonezawa, Akihito; Tsukada, Junichi; Mukae, Hiroshi

    2016-01-01

    A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia. PMID:27374685

  8. Fatal Case of Brucellosis Misdiagnosed in Early Stages of Brucella suis Infection in a 46-Year-Old Patient with Marfan Syndrome

    PubMed Central

    Carrington, M.; Choe, U.; Ubillos, S.; Stanek, D.; Campbell, M.; Wansbrough, L.; Lee, P.; Churchwell, G.; Rosas, K.; Zaki, S. R.; Drew, C.; Paddock, C. D.; DeLeon-Carnes, M.; Guerra, M.; Hoffmaster, A. R.; Tiller, R. V.

    2012-01-01

    We report a fatal case of Brucella suis endocarditis initially misdiagnosed by automated identification systems as Ochrobactrum anthropi infection in a patient with a history of Marfan syndrome and recreational feral swine hunting. This report emphasizes the need to consider brucellosis as a part of the differential diagnosis of acute febrile illness, particularly in patients with known risk of exposure. PMID:22495564

  9. [The nature of changes of some immunophysiological characteristics in bream (Abramis brama) infected with plerocercoids (Ligula intestinalis) at various stages of parasite development].

    PubMed

    Silkina, N I; Mikriakov, V R; Mikriakov, D V

    2012-01-01

    The data from studies of the antimicrobial properties of blood serum, the content of total lipids, and antioxidant activity of immunocompetent tissues and organs of breams Abramis brama infected with plerocercoids Ligula intestinalis depending on the phase of development of the parasite are presented. The quantitative characteristics of the studied parameters are determined. PMID:23136746

  10. Antimicrobial peptides in the duodenum at the acute and convalescent stages in patients with diarrhea due to Vibrio cholerae O1 or enterotoxigenic Escherichia coli infection.

    PubMed

    Shirin, Tahmina; Rahman, Arman; Danielsson, Åke; Uddin, Taher; Bhuyian, Taufiqur Rahman; Sheikh, Alaullah; Qadri, Syed Saleheen; Qadri, Firdausi; Hammarström, Marie-Louise

    2011-11-01

    Patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) were analyzed for innate immune factors produced by the epithelium during the disease process. Duodenal biopsies were obtained from study participants at the acute (day 2) and convalescent (day 21) stages of disease. Levels of α-defensin (HD-5 and -6), β-defensin (hBD-1-4), and cathelicidin (LL-37) mRNAs were determined by real-time qRT-PCR. hBD-2, HD-5, LL-37 peptides were analyzed in duodenal epithelium by immunomorphometry. Concentration of hBD-2 in stool was determined by ELISA. Specimens from healthy controls were also analyzed. hBD-2 mRNA levels were significantly increased at acute stage of diarrhea; hBD-2 peptide was detected in fecal specimens but barely in duodenal epithelium at acute stage. Immunomorphometry analysis showed that Paneth cells contain significantly higher amounts of HD-5 pre/propeptide at convalescence (P<0.01) and in healthy controls (P<0.001) compared to acute stage, LL-37 peptide levels also decreased at acute stage while mRNA levels remained unchanged. mRNA expression levels of the other antimicrobial peptides remained unchanged with higher levels of α-defensins than β-defensins. V. cholerae induced an innate immune response at the acute stage of disease characterized by increased expression of hBD-2, and continued expression of hBD-1, HD-5-6, and LL-37. PMID:21782033

  11. 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.

  12. Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR

    PubMed Central

    2013-01-01

    Background Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. BLV infection may remain clinically silent at the aleukemic (AL) stage, cause persistent lymphocytosis (PL), or, more rarely, B cell lymphoma. BLV has been identified in B cells, CD2+ T cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, γ/δ T cells, monocytes, and granulocytes in infected cattle that do not have tumors, although the most consistently infected cell is the CD5+ B cell. The mechanism by which BLV causes uncontrolled CD5+ B cell proliferation is unknown. Recently, we developed a new quantitative real-time polymerase chain reaction (PCR) method, BLV-CoCoMo-qPCR, which enabled us to demonstrate that the proviral load correlates not only with BLV infection, as assessed by syncytium formation, but also with BLV disease progression. The present study reports the distribution of BLV provirus in peripheral blood mononuclear cell subpopulations isolated from BLV-infected cows at the subclinical stage of EBL as examined by cell sorting and BLV-CoCoMo-qPCR. Results Phenotypic characterization of five BLV-infected but clinically normal cattle with a proviral load of > 100 copies per 1 × 105 cells identified a high percentage of CD5+ IgM+ cells (but not CD5- IgM+ B cells, CD4+ T cells, or CD8+T cells). These lymphocyte subpopulations were purified from three out of five cattle by cell sorting or using magnetic beads, and the BLV proviral load was estimated using BLV-CoCoMo-qPCR. The CD5+ IgM+ B cell population in all animals harbored a higher BLV proviral load than the other cell populations. The copy number of proviruses infecting CD5- IgM+ B cells, CD4+ cells, and CD8+ T cells (per 1 ml of blood) was 1/34 to 1/4, 1/22 to 1/3, and 1/31 to 1/3, respectively, compared with that in CD5+ IgM+ B cells. Moreover, the BLV provirus remained integrated into the genomic DNA of CD5+ IgM+ B cells, CD5- IgM+ B cells, CD4+ T

  13. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

    PubMed Central

    Schuitemaker, H; Koot, M; Kootstra, N A; Dercksen, M W; de Goede, R E; van Steenwijk, R P; Lange, J M; Schattenkerk, J K; Miedema, F; Tersmette, M

    1992-01-01

    The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood. PMID:1738194

  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. PMID:26518036

  15. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium.

    PubMed

    Lyte, Mark; Li, Wang; Opitz, Noel; Gaykema, Ronald P A; Goehler, Lisa E

    2006-10-30

    Symptoms of anxiety frequently occur concomitant to the development and persistence of inflammatory bowel disease (IBD) in patients. In the present study, we utilized an animal model of IBD, infection with Citrobacter rodentium, to determine whether the infection per se can drive anxiety-like behavior. Nine-week-old CF-1 male mice were challenged orally with either saline or C. rodentium. Early in the infective process (7-8 h later), mice were tested on a hole-board open field apparatus for anxiety-like behavior measurement. Immediately following behavioral testing, plasma samples were obtained for immune cytokine analysis and colons were excised for histological analysis. In additional animals, vagal ganglia were removed and processed for c-Fos protein detection. Challenge with C. rodentium significantly increased anxiety-like behavior as evidenced by avoidance of the center area and increased risk assessment behavior. Plasma levels of the cytokines IFN-gamma, TNF-alpha and IL-12 were not different. However vagal sensory ganglia from C. rodentium-treated animals evinced significantly more c-Fos protein-positive neurons, consistent with vagal afferent transmission of C. rodentium-related signals from gut to brain. Histological examination of the colon indicated a lack of overt inflammation at the 8 h post-challenge time point, indicating that the differences in behavior were unlikely to follow from inflammation-related stress. The results of the present study demonstrate that infection with C. rodentium can induce anxiety-like symptoms that are likely mediated via vagal sensory neurons. PMID:16887154

  16. Characterization of tuberculous granulomas in different stages of progression and associated tertiary lymphoid tissue in goats experimentally infected with Mycobacterium avium subsp. hominissuis.

    PubMed

    Schinköthe, Jan; Köhler, Heike; Liebler-Tenorio, Elisabeth M

    2016-08-01

    Oral infection of goats with Mycobacterium avium subsp. hominissuis (MAH) resulted in a large variety of granulomas in organized gut-associated lymphatic tissues and intestinal lymph nodes. To characterize the cellular composition of granulomas, CD4(+), CD8(+), γδ, B lymphocytes and plasma, CD25(+), CD68(+), MHC-II(+), Ki67(+) and endothelial cells were labeled in consecutive frozen sections by immunohistochemistry and acid fast bacilli (AFB) by Kinyoun stain. Granulomas with extensive necrosis, little mineralization and variable numbers of AFB surrounded by many CD4(+) T cells, but only few epitheloid macrophages were observed in severely sick goats at 2-3mpi. They were interpreted as exuberant immune reaction. Organized granulomas with very few AFB were seen in clinically healthy goats at 13mpi. The necrotic cores were surrounded by a zone of granulomatous infiltrate with many epitheloid macrophages and few lymphocytes. This zone was initially wide and highly vascularized and became progressively smaller. It was enclosed by an increasing layer of connective tissue. All organized granulomas were surrounded by compartimentalized tertiary lymphoid tissue. The granulomas in experimental infection of goats with MAH reflect the heterogeneity of lesions seen in mycobacterial infections of humans and ruminants and are therefore valuable for comparative research. PMID:27477506

  17. Sequential Phase 1 and Phase 2 randomized, controlled trials of the safety, immunogenicity and efficacy of combined pre-erythrocytic vaccine antigens RTS,S and TRAP formulated with AS02 Adjuvant System in healthy, malaria naïve adults.

    PubMed

    Kester, Kent E; Gray Heppner, D; Moris, Philippe; Ofori-Anyinam, Opokua; Krzych, Urszula; Tornieporth, Nadia; McKinney, Denise; Delchambre, Martine; Ockenhouse, Christian F; Voss, Gerald; Holland, Carolyn; Beckey, Jolie Palensky; Ballou, W Ripley; Cohen, Joe

    2014-11-20

    In an attempt to improve the efficacy of the candidate malaria vaccine RTS,S/AS02, two studies were conducted in 1999 in healthy volunteers of RTS,S/AS02 in combination with recombinant Plasmodium falciparum thrombospondin-related anonymous protein (TRAP). In a Phase 1 safety and immunogenicity study, volunteers were randomized to receive TRAP/AS02 (N=10), RTS,S/AS02 (N=10), or RTS,S+TRAP/AS02 (N=20) at 0, 1 and 6-months. In a Phase 2 challenge study, subjects were randomized to receive either RTS,S+TRAP/AS02 (N=25) or TRAP/AS02 (N=10) at 0 and 1-month, or to a challenge control group (N=8). In both studies, the combination vaccine had an acceptable safety profile and was acceptably tolerated. Antigen-specific antibodies, lymphoproliferative responses, and IFN-γ production by ELISPOT assay elicited with the combination vaccine were qualitatively similar to those generated by the single component vaccines. However, post-dose 2 anti-CS antibodies in the RTS,S+TRAP/AS02 vaccine recipients were lower than in the RTS,S/AS02 vaccine recipients. After challenge, 10 of 11 RTS,S+TRAP/AS02 vaccinees, 5 of 5 TRAP/AS02 vaccinees, and 8 of 8 infectivity controls developed parasitemia, with median pre-patent periods of 13.0, 11.0, and 12.0 days, respectively. The absence of any prevention or delay of parasitemia by TRAP/AS02 suggests no apparent added value of TRAP/AS02 as a candidate vaccine. The absence of significant protection or delay of parasitemia in the 11 RTS,S+TRAP/AS02 vaccine recipients contrasts with previous 2 dose studies of RTS,S/AS02. The small sample size did not permit identifying statistically significant differences between the study arms. However, we speculate, within the constraints of the challenge study, that the presence of the TRAP antigen may have interfered with the vaccine efficacy previously observed with this regimen of RTS,S/AS02, and that any future TRAP-based vaccines should consider employing alternative vaccine platforms. PMID:24950358

  18. Oncogenic Virus Infections in the General Population and End-stage Renal Disease Patients With Special Emphasis on Kaposi’s Sarcoma Associated Herpes Virus (KSHV) in Northeast of Iran

    PubMed Central

    Ahmadi Ghezeldasht, Sanaz; Hassannia, Tahereh; Rafatpanah, Houshang; Hekmat, Reza; Valizadeh, Narges; Ghayour Mobarhan, Majid; Rezaee, Seyed Abdolrahim

    2015-01-01

    Background: Globally, almost 20% of cancers are related to infectious agents that can be prevented. Oncogenicity refers to viruses that may cause cancers, more importantly in immunocompromised subjects such as transplant and hemodialysis patients. Therefore, epidemiological studies are the first line for understanding the importance of these agents in public health, particularly, in mobile populations, tourism and pilgrimage regions. Objectives: Oncogenic viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and Epstein-barr virus (EBV) are the most common viral agents in immunocompromised patients. Furthermore, human T lymphocyte virus type I (HTLV-I), due to endemicity in Khorasan Razavi province located northeast of Iran as a pilgrimage region, and Kaposi's sarcoma associated herpes virus (KSHV), as an oncogenic herpesvirus in immunocompromised subjects have been investigated among the general population and those with end-stage renal diseases (ESRD). Patients and Methods: A cross-sectional study was carried out among 1227 randomly selected individuals; 25 donors and 195 patients with ESRD, including 60 kidney transplant recipients and 135 dialysis patients from the Khorasan Razavi province, Iran. Serological tests were carried out using commercial enzyme-immunoassay kits. To confirm positive serology tests, the extracted viral DNA or RNA was examined for the presence of KSHV, HTLV-I and HCV by conventional PCR. Results: The prevalence of KSHV infection in the general population was 1.71% (21/1227); 2.60% (10/384) males and 1.30% (11/843) females. In kidney transplants, viral infections occurred in 23.3% of subjects; including EBV, HTLV-I and HBV-HCV co-infection in 8.3%, 3.3% and 1.7%, respectively. In patients on hemodialysis, viral infections were present in 29.6% including EBV, HTLV-I and HBV-HCV co-infection in 2.2%, 5.9% and 16.3%, respectively. Seroprevalence of KSHV in patients with kidney transplants was 1.7% and in patients on

  19. 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

  20. 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

    Rajendran, Vinoth; Rohra, Shilpa; Raza, Mohsin; Hasan, Gulam Mustafa; Dutt, Suparna; Ghosh, Prahlad C

    2016-03-01

    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 [(3)H]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

  1. Assessment of quality of life in early stage HIV-infected persons: data from the AIDS Time-oriented Health Outcome Study (ATHOS).

    PubMed

    Lubeck, D P; Fries, J F

    1997-08-01

    The development of new pharmaceutical interventions for persons with human immunodeficiency virus (HIV) infection has resulted in extended survival and a need for valid, reliable and responsive instruments to assess health-related QoL (HRQoL). This paper reviews the reliability and validity of an HRQoL instrument, the AIDS Health Assessment Questionnaire (AIDS-HAQ), among persons participating in an observational database of HIV infection. The AIDS-HAQ includes nine subscales: disability, energy, general health, pain, cognitive functioning, mental health, social functioning, health distress and symptoms. Individuals complete the AIDS-HAQ quarterly. Data are reported for 440 individuals entering the study with early HIV infection. Fifty-nine progressed to symptomatic disease and 109 to AIDS after 1 year. The subscales of the instrument resulted in high internal consistency reliability (range = 0.79-0.88). Concurrent validity data reflected the ability to distinguish between patients with increasing disease severity. In all domains, except cognitive functioning, individuals who progressed to AIDS had significant decrements (p < 0.01) in HRQoL compared with symptomatic and asymptomatic patients. Significant decrements (p < 0.01) were observed for disability, general health, energy and symptoms for patients who progressed to symptomatic disease from an asymptomatic status. Individuals who had decreasing CD4+ counts also had significant declines (p < 0.001) in disability, general health, social functioning, pain and symptoms. The AIDS-HAQ is an instrument that can be used when comparing group differences and within group changes in observational databases, naturalistic studies and clinical trials. PMID:9330550

  2. [Platelet activating factor in biological fluids of animals with different species-specific resistance at the stage of infective process after inoculation with mycobacterium tuberculosis].

    PubMed

    Kaminskaia, G O; Abdullaev, R Iu; Gedymin, L E

    1998-01-01

    Following 24 hours, 1, 2, and 6 weeks of inoculation of guinea-pigs and albino rats by Mycobacterium tuberculosis (MT), the levels of platelet activation factor (PAF) were determined in the plasma, leukocytes, alveolar macrophages, nonfractionated cellular sediment and fluid of bronchoalveolar lavage (FBAL) by testing rabbit platelets. The guinea-pigs developed generalized tuberculosis, the rats receiving a small dose of MT developed nonspecific inflammation and those taking a large dose had specific foci. In both experiments, spontaneous regression of inflammatory changes began in rats after 6 weeks. In the guinea-pigs inoculated by MT, there was a steady increase in PAF synthesis in all cell populations, PAF levels dropped in fluids. In the rats receiving a small dose of MT, the cellular levels PAF levels periodically rose in early infection, but decreased below the control values during regression of inflammatory changes. Concurrently, the level of PAF became lower in plasma and FBAL. With high-dose inoculation, it drastically fell in the cells just after MT administration, then moderately increased during the development of specific changes and again dropped at the end of the experiment. In early infection the changes in PAF levels in the body's fluids were mirror as regards to the respective cells, but at regression of specific changes, the content of PAF was lower than the normal values in all the fluids under study. PMID:10067355

  3. Interferon-Based Treatment of Hepatitis C Virus Infection Reduces All-Cause Mortality in Patients With End-Stage Renal Disease: An 8-Year Nationwide Cohort Study in Taiwan.

    PubMed

    Hsu, Yueh-Han; Hung, Peir-Haur; Muo, Chih-Hsin; Tsai, Wen-Chen; Hsu, Chih-Cheng; Kao, Chia-Hung

    2015-11-01

    The long-term survival of end-stage renal disease (ESRD) patients with hepatitis C virus (HCV) infection who received interferon treatment has not been extensively evaluated.The HCV cohort was the ESRD patients with de novo HCV infection from 2004 to 2011; they were classified into treated and untreated groups according to interferon therapy records. Patients aged <20 years and those with a history of hepatitis B, kidney transplantation, or cancer were excluded. The control cohort included ESRD patients without HCV infection matched 4:1 to the HCV cohort by age, sex, and year of ESRD registration. We followed up all study participants until kidney transplantation, death, or the end of 2011, whichever came first. We assessed risk of all-cause mortality by using the multivariate Cox proportional hazard model with time-dependent covariate.In the HCV cohort, 134 patients (6.01%) received interferon treatment. Compared with the uninfected control cohort, the treated group had a lower risk of death (hazard ratio 0.47, 95% confidence interval [CI] 0.22-0.99). The untreated group had a 2.62-fold higher risk (95% CI 1.24-5.55) of death compared with the treated group. For the HCV cohort without cirrhosis or hepatoma, the risk of death in the treated group was further markedly reduced (hazard ratio 0.17, 95% CI 0.04-0.68) compared with that in the control cohort.For ESRD patients with HCV infection, receiving interferon treatment is associated with a survival advantage. Such an advantage is more prominent in HCV patients without cirrhosis or hepatoma. PMID:26632730

  4. 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

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

    ClinicalTrials.gov

    2016-09-09

    AIDS-Related Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Stage IIA Hodgkin Lymphoma; Stage IIB Hodgkin Lymphoma; Stage IIIA Hodgkin Lymphoma; Stage IIIB Hodgkin Lymphoma; Stage IVA Hodgkin Lymphoma; Stage IVB Hodgkin Lymphoma

  6. Close interactions between sympathetic neural fibres and follicular dendritic cells network are not altered in Peyer's patches and spleen of C57BL/6 mice during the preclinical stage of 139A scrapie infection.

    PubMed

    Demonceau, Caroline; Piret, Joelle; Zorzi, Danièle; Thellin, Olivier; Heinen, Ernst

    2014-07-15

    During preclinical stage of prion diseases, secondary lymphoid organs seem to play an important role in prion amplification prior the invasion of the associated peripheral nervous system. In mice, it was shown that the relative positioning of follicular dendritic cells (FDC) and sympathetic nervous system (SNS) affects the velocity of neuroinvasion following scrapie inoculation. In this study, we checked if scrapie infection, by oral or intraperitoneal route, could influence this neuroimmune interface between FDC and tyrosine hydroxylase (TH) positive neural fibres within Peyer's patches (PP) and spleen of the C57BL/6 mouse strain. We concluded that, in vivo, scrapie 139A and ME7 strains do not modify FDC-SNS neuroimmune interface. However, age seems to alter this neuroimmune interface and thus could influence the neuroinvasion in prion pathogenesis. PMID:24841625

  7. 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 ...

  8. Identification of MBF2 family genes in Bombyx mori and their expression in different tissues and stages and in response to Bacillus bombysepticus infection and starvation.

    PubMed

    Zhou, Chun-Yan; Zha, Xing-Fu; Liu, Chun; Han, Min-Jin; Zhang, Li-Ying; Shi, Pan-Pan; Wang, He; Zheng, Ren-Wen; Xia, Qing-You

    2016-08-01

    The Multiprotein bridge factor 2 (MBF2) gene was first identified as a co-activator involved in BmFTZ-F1-mediated activation of the Fushi tarazu gene. Herein, nine homologous genes of MBF2 gene are identified. Evolutionary analysis showed that this gene family is insect-specific and that the family members are closely related to response to pathogens (REPAT) genes. Tissue distribution analysis revealed that these genes could be expressed in a tissue-specific manner. Developmental profiles analysis showed that the MBF2 gene family members were highly expressed in the different stages. Analysis of the expression patterns of nine MBF2 family genes showed that Bacillus bombysepticus treatment induced the up-regulation of several MBF2 family genes, including MBF2-4, -7, -9, -8. Furthermore, we found the MBF2 family genes were modulated by starvation and the expression of these genes recovered upon re-feeding, except for MBF2-5, -9. These findings suggested roles for these proteins in insect defense against pathogens and nutrient metabolism, which has an important guiding significance for designing pest control strategies. PMID:27121992

  9. 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 Central

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

    2015-01-01

    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. PMID:26008237

  10. 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 Central

    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.; Khan, Sheik Humarr

    2015-01-01

    Abstract 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. PMID:25531344

  11. 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. PMID:25531344

  12. The comparative efficacy of abamectin, monepantel and an abamectin/derquantel combination against fourth-stage larvae of a macrocyclic lactone-resistant Teladorsagia spp. isolate infecting sheep.

    PubMed

    George, S D; George, A J; Stein, P A; Rolfe, P F; Hosking, B C; Seewald, W

    2012-08-13

    Anthelmintic resistance by gastrointestinal nematodes of sheep continues to be an issue of global interest. While the recent introduction in some countries of one or two new anthelmintic classes (amino-acetonitrile derivatives [AAD] and spiroindoles [SI]) has been welcomed, it is important that there is no relaxation in parasite control and the management of drug resistance. Monepantel (an AAD) was the first new anthelmintic to be approved for use (New Zealand, 2009) and was followed a year later in the same country by a combination of derquantel (a SI) and abamectin. The present study determined the efficacy of the new anthelmintic products and abamectin against fourth-stage larvae of macrocyclic lactone-resistant Teladorsagia spp. in lambs. Efficacies were calculated by comparing post-mortem nematode burdens of treated animals with those of untreated control sheep, and were 98.5, 86.3 and 34.0% for monepantel, abamectin/derquantel and abamectin, respectively. The nematode burdens of monepantel- and abamectin/derquantel-treated sheep were significantly lower than those sheep treated with abamectin and the untreated controls. Similarly, the burden of the monepantel group was significantly lower than that of the abamectin/derquantel group. These findings provide an opportunity to reinforce the recommendation that farmers and animal health advisors need to know the resistance status of nematode populations on subject farms to ensure effective control programs are designed and implemented. Such control programs should include an appropriate choice of anthelmintic(s), monitoring parasite burdens for correct timing of treatments, and pasture management to reduce larval challenge balanced with the maintenance of drug-susceptible populations in refugia. PMID:22459111

  13. 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

  14. 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…

  15. Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

    PubMed Central

    Mizutani, Masanori; Iyori, Mitsuhiro; Blagborough, Andrew M.; Fukumoto, Shinya; Funatsu, Tomohiro; Sinden, Robert E.

    2014-01-01

    A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. PMID:25092912

  16. Infection and Other Complications

    MedlinePlus

    ... Stage 3 Infection and Other Complications NLN Position Papers Lymphedema Awareness Campaign Education Kits Educational Videos What ... Patients (8) LymphLink Articles (175) FAQ's (6) Position Papers (9) LSAP Perspective (9) Become a member now » ...

  17. Stages of Anal Cancer

    MedlinePlus

    ... following stages are used for anal cancer: Stage 0 (Carcinoma in Situ) In stage 0 , abnormal cells ... or check-ups. Treatment Options by Stage Stage 0 (Carcinoma in Situ) Treatment of stage 0 is ...

  18. Stages and Behaviors

    MedlinePlus

    ... Stage Caregiving Middle-Stage Caregiving Late-Stage Caregiving Behaviors Aggression & Anger Anxiety & Agitation Depression Hallucinations Memory Loss & ... Legal Documents alz.org » Caregiver Center » Stages and Behaviors Text size: A A A Stages / Behaviors As ...

  19. 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 ...

  20. [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. PMID:27509655

  1. 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

  2. Bone and Joint Infections in Older Adults.

    PubMed

    Mears, Simon C; Edwards, Paul K

    2016-08-01

    Bone and joint infections in the elderly patient include septic native joints, osteomyelitis, and prosthetic joint infection. Infections are difficult to treat and require a team approach. Surgical debridement and intravenous antibiotics are the keys to treatment. Prosthetic joint infections often need a two-stage approach to treatment. First the infected joint is removed and the infection treated, then a second prosthetic joint is placed. Prosthetic joint infection is becoming the most common complication after joint replacement surgery. Outcomes of treatment of bone and joint infections are related to the severity of the infection and condition of the host. Because the elderly are often frail, treatment is challenging. PMID:27394023

  3. 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 ...

  4. Meningococcal Infections

    MedlinePlus

    ... are a type of bacteria that cause serious infections. The most common infection is meningitis, which is an inflammation of the ... also cause other problems, including a serious bloodstream infection called sepsis. Meningococcal infections can spread from person ...

  5. Infections in Liver Disease.

    PubMed

    Nanchal, Rahul S; Ahmad, Shahryar

    2016-07-01

    Infectious complications are common occurrences in end-stage liver disease (ESLD). Frequent infections precipitate decompensation of liver disease leading to acute or chronic liver failure, organ dysfunction, de-listing from transplant, and major morbidity and mortality. The spectrum of microorganisms has shifted with the emergence of multidrug-resistant strains, which has major implications for both therapy and prophylaxis. Cirrhosis is often associated with an underlying noninfectious systemic inflammatory state that makes diagnosis of infections particularly challenging. Adequate resuscitation and timely administration of appropriate antibiotics are pivotal to improved outcomes from infections in ESLD. PMID:27339680

  6. Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer

    ClinicalTrials.gov

    2016-06-20

    Human Papillomavirus Infection; Salivary Gland Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

  7. Pancreatic Cancer Stage 3

    MedlinePlus

    ... historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...

  8. 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 ...

  9. Hookworm infection

    MedlinePlus

    Hookworm disease; Ground itch; Ancylostoma duodenale infection; Necator americanus infection; Parasitic infection - hookworm ... in getting the disease is walking barefoot on ground where there are feces of people who have ...

  10. Yeast Infections

    MedlinePlus

    ... antibiotics, it can multiply and cause an infection. Yeast infections affect different parts of the body in different ways: Thrush is a yeast infection that causes white patches in your mouth Candida ...

  11. Vaginal Infections

    MedlinePlus

    ... Two common vaginal infections are bacterial vaginosis and yeast infections . Bacterial vaginosis (BV) happens when a certain ... increases the chances that you’ll get BV. Yeast infections happen when a fungus (a type of ...

  12. Bone Infections

    MedlinePlus

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  13. Eye Infections

    MedlinePlus

    Your eyes can get infections from bacteria, fungi, or viruses. Eye infections can occur in different parts of the eye and can affect just one eye or both. Two common eye infections are Conjunctivitis - also known as pinkeye. Conjunctivitis is ...

  14. Proviral activation of the c-myb proto-oncogene is detectable in preleukemic mice infected neonatally with Moloney murine leukemia virus but not in resulting end stage T lymphomas.

    PubMed

    Belli, B; Wolff, L; Nazarov, V; Fan, H

    1995-08-01

    Moloney murine leukemia virus induces myeloid leukemia when inoculated intravenously into pristane-primed adult BALB/c mice. One hundred percent of these tumors show insertional activation of the c-myb proto-oncogene, and reverse transcriptase PCR assays have shown that the c-myb activation could be detected soon after infection. We tested BALB/c and NIH Swiss mice that had been inoculated as newborns with Moloney murine leukemia virus, under which conditions they develop T lymphomas exclusively. Reverse transcriptase-PCR assays indicated that c-myb activations were detectable soon after neonatal infection. However, none of the resulting T lymphomas contained c-myb activations. The implications of these results to the timing of proto-oncogene activations in leukemogenesis and the specificity of proto-oncogene activations for different diseases are discussed. PMID:7609084

  15. Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.

    PubMed

    Loughland, Jessica R; Minigo, Gabriela; Burel, Julie; Tipping, Peta E; Piera, Kim A; Amante, Fiona H; Engwerda, Christian R; Good, Michael F; Doolan, Denise L; Anstey, Nicholas M; McCarthy, James S; Woodberry, Tonia

    2016-05-01

    Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c(+) mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c(+) mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c(+) mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c(+) mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c(+) mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c(+) mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion. PMID:26902728

  16. 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 Central

    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. PMID:26649443

  17. PIRO concept: Staging of sepsis

    PubMed Central

    Rathour, S; Kumar, S; Hadda, V; Bhalla, A; Sharma, N; Varma, S

    2015-01-01

    Introduction: Sepsis is common presenting illness to the emergency services and one of the leading causes of hospital mortality. Researchers and clinicians have realized that the systemic inflammatory response syndrome concept for defining sepsis is less useful and lacks specificity. The predisposition, infection (or insult), response and organ dysfunction (PIRO) staging of sepsis similar to malignant diseases (TNM staging) might give better information. Materials and Methods: A prospective observational study was conducted in emergency medical services attached to medicine department of a tertiary care hospital in Northern India. Patients with age 18 years or more with proven sepsis were included in the first 24 hours of the diagnosis. Two hundred patients were recruited. Multivariate logistic regression analysis was done to assess the factors that predicted in-hospital mortality. Results: Two hundred patients with proven sepsis, admitted to the emergency medical services were analysed. Male preponderance was noted (M: F ratio = 1.6:1). Mean age of study cohort was 50.50 ± 16.30 years. Out of 200 patients, 116 (58%) had in-hospital mortality. In multivariate logistic regression analysis, the factors independently associated with in-hospital mortality for predisposition component of PIRO staging were age >70 years, chronic obstructive pulmonary disease, chronic liver disease, cancer and presence of foley's catheter; for infection/insult were pneumonia, urinary tract infection and meningitis/encephalitis; for response variable were tachypnea (respiratory rate >20/minute) and bandemia (band >5%). Organ dysfunction variables associated with hospital mortality were systolic blood pressure <90mm Hg, prolonged activated partial thromboplastin time, raised serum creatinine, partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio <300, decreased urine output in first two hours of emergency presentation and Glasgow coma scale ≤9. Each

  18. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, V E J; Stam, E D; Welborn, K M; Sas, T C J

    2016-01-01

    Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease. PMID:27122069

  19. Cervical Cancer Stage IIIB

    MedlinePlus

    ... Cancer Stage IIIB Description: Stage IIIB cervical cancer; drawing shows cancer in the cervix, the vagina, and ... that connect the kidneys to the bladder). The drawing shows the ureter on the right blocked by ...

  20. 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. ...

  1. Cervical Cancer Stage IVB

    MedlinePlus

    ... of the body, such as the lymph nodes, lung, liver, intestine, or bone. Stage IVB cervical cancer. Topics/Categories: Anatomy -- Gynecologic Cancer Types -- Cervical Cancer Staging Type: Color, Medical Illustration Source: National Cancer Institute ...

  2. 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.

  3. 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 ...

  4. Current systems: Upper stages

    NASA Technical Reports Server (NTRS)

    Gunn, Charles R.

    1991-01-01

    The United States orbital transfer vehicles are presented: PAM-D (Payload Assist Module); PAM-D2; IUS (Inertial Upper Stage); and TOS (Transfer Orbit Stage). This presentation is represented by viewgraphs.

  5. OxyR and SoxR modulate the inducible oxidative stress response and are implicated during different stages of infection for the bacterial phytopathogen Pantoea stewartii subsp. stewartii.

    PubMed

    Burbank, Lindsey; Roper, M Caroline

    2014-05-01

    Reactive oxygen species (ROS) from a variety of sources are often encountered by invading plant pathogens during the infection process. Pantoea stewartii subsp. stewartii, the etiological agent of Stewart's wilt, is a serious bacterial pathogen of sweet corn that colonizes both the apoplast and xylem tissues in which ROS are produced. The P. stewartii genome predicts the presence of two redox-sensing transcriptional regulators, OxyR and SoxR, which both activate gene expression in response to oxidative stress. ROS exposure in the form of hydrogen peroxide and the superoxide-generating compound paraquat initiates an induced stress response through OxyR and SoxR that includes activation of the ROS-detoxifying enzymes alkyl hydroperoxide reductase and superoxide dismutase. P. stewartii ΔsoxR was more sensitive to paraquat and was compromised in the ability to form water-soaked lesions, while ΔoxyR was more sensitive to hydrogen peroxide treatment and was deficient in exopolysaccharide production and the elicitation of wilting symptoms. This demonstrates that both SoxR and OxyR play an important role in virulence in the different niches that P. stewartii colonize during the infection process. PMID:24450773

  6. HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

    ClinicalTrials.gov

    2016-09-06

    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

  7. 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)

  8. Cervical Cancer Stage IA

    MedlinePlus

    ... historical Searches are case-insensitive Cervical Cancer Stage IA Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Cervical Cancer Stage IA Description: Stage IA1 and IA2 cervical cancer; drawing ...

  9. 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 ...

  10. 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 ...

  11. Ovarian Cancer Stage II

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage II Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage ...

  12. Ovarian Cancer Stage I

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage I Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage I Description: Three-panel drawing of stage ...

  13. 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

  14. 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. PMID:17166598

  15. 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

  16. Tree Growth Stage and Environment after Pathogen Inoculation Alters Susceptibility of Pear Trees to Phytophthora Canker

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated whether growth stage of pear (Pyrus communis) tree rootstock and environment after inoculation with Phytophthora syringae influences tree susceptibility to infection. Trees at different stages of dormancy development were inoculated with the pathogen and maintained in different condi...

  17. 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 ...

  18. 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 ...

  19. Infection Control

    MedlinePlus

    ... lost because of the spread of infections in hospitals. Health care workers can take steps to prevent the spread of infectious diseases. These steps are part of infection control. Proper hand washing is the most effective way ...

  20. Staphylococcal Infections

    MedlinePlus

    ... Most staph skin infections are easily treated with antibiotics or by draining the infection. Some staph bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) are resistant to certain antibiotics, making ...

  1. Staphylococcal Infections

    MedlinePlus

    ... best way to prevent staph is to keep hands and wounds clean. Most staph skin infections are easily treated with antibiotics or by draining the infection. Some staph bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) are ...

  2. Spinal Infections

    MedlinePlus

    ... Surgical risk factors include a long surgical time, instrumentation and re-operations. Infections occur in up to 4% of surgical cases despite the numerous preventative measures that are taken. The likelihood of an infection ...

  3. Bacterial Infections

    MedlinePlus

    ... make you sick. Examples of bacteria that cause infections include Streptococcus, Staphylococcus, and E. coli. Antibiotics are the usual treatment. When you take antibiotics, follow the directions carefully. Each ... infection that those antibiotics cannot cure. NIH: National Institute ...

  4. Gastrointestinal Infections.

    PubMed

    Alby, Kevin; Nachamkin, Irving

    2016-06-01

    Gastrointestinal infections in the immunocompromised host are caused by the common bacterial, viral, fungal, and parasitic agents that also cause infections in the immunocompetent host. Of special consideration is that immunocompromised patients may be at increased risk for infection or disease severity and by pathogens not seen in the competent host. This chapter reviews the various agents, risk factors, and diagnostic approaches to detect gastrointestinal infections in this patient population. PMID:27337464

  5. 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.

  6. 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.

  7. Staging of hepatocellular carcinoma.

    PubMed

    Duseja, Ajay

    2014-08-01

    Hepatocellular carcinoma (HCC) is different from other malignancies because the prognosis in HCC is not only dependent upon the tumor stage but also on the liver function impairment due to accompanying cirrhosis liver. Various other staging systems used in HCC include the European systems [French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system and the cancer of the liver Italian program (CLIP)] and Asian systems [Okuda staging system, Japan integrated Staging (JIS), Tokyo score and Chinese University Prognostic Index (CUPI)]. Out of all the staging systems used in HCC, Barcelona Clinic Liver Cancer (BCLC) staging system is probably the best because it takes in to account the tumor status (defined by tumor size and number, presence of vascular invasion and extrahepatic spread), liver function (defined either by the Child-Pugh's class) and general health status of the patient (defined by the ECOG classification and the presence of symptoms). Since most of the extrahepatic spread in HCC occurs to lymph nodes, lungs and bones, the assessment can be done with either PET/CT or a combination of CT (Chest and abdomen) and a bone scan. This article describes the various staging systems used in HCC, guides choosing a staging system particularly in the Indian context and the assessment of extra-hepatic spread in HCC. PMID:25755615

  8. Imaging liver-stage malaria parasites.

    PubMed

    Rankin, Kathleen E; Graewe, Stefanie; Heussler, Volker T; Stanway, Rebecca R

    2010-05-01

    Plasmodium parasites, the causative agents of malaria, first invade and develop within hepatocytes before infecting red blood cells and causing symptomatic disease. Because of the low infection rates in vitro and in vivo, the liver stage of Plasmodium infection is not very amenable to biochemical assays, but the large size of the parasite at this stage in comparison with Plasmodium blood stages makes it accessible to microscopic analysis. A variety of imaging techniques has been used to this aim, ranging from electron microscopy to widefield epifluorescence and laser scanning confocal microscopy. High-speed live video microscopy of fluorescent parasites in particular has radically changed our view on key events in Plasmodium liver-stage development. This includes the fate of motile sporozoites inoculated by Anopheles mosquitoes as well as the transport of merozoites within merosomes from the liver tissue into the blood vessel. It is safe to predict that in the near future the application of the latest microscopy techniques in Plasmodium research will bring important insights and allow us spectacular views of parasites during their development in the liver. PMID:20180802

  9. [Immunodepression and pulmonary infections].

    PubMed

    Yao, N A; Ngoran, N; de Jaureguiberry, J P; Bérard, H; Jaubert, D

    2002-11-01

    The acquired immunosuppressed states are increasingly numerous. Pneumopathies are a frequent, serious complication and etiologic diagnosis is often difficult. The nature of the micro-organism in question is a function of the immunizing type of deficiency. In neutropenias, the infections are primarily bacterial, their potential gravity being correlated with the depth of the deficiency into polynuclear, or fungic, especially in prolonged neutropenias. The aspleened states are responsible for a deficit of the macrophage system and contribute to the infections with encapsulated germs (pneumococci, klebsiellas...). The organic grafts imply an attack of cell-mediated immunity, in the particular case of the auxiliary T lymphocytes (CD4)), with a special predisposition for viral and fungic infections. During VIH infection, the immunizing deficit of CD4 lymphocytes worsens with time. At the early stage, the infections are especially bacterial. At the more advanced stages, the pulmonary pneumocystosis and tuberculosis dominate. At the late stage, finally, deep immunosuppression allows emerging of the atypical mycobacteries. In the deficiencies of humoral immunity (congenital hypogammaglobulinemias, lymphoid hemopathies B), the germs to be mentioned are the pneumococcus, Haemophilus influenzae, the salmonellas and the legionellas. Immunosuppressed pneumopathies are characterized by radio-clinical pictures of very variable gravity, ranging from focused acute pneumopathy to bilateral diffuse pneumopathy with acute respiratory distress syndrome, with phases of atypical tables with respiratory symptomatology larval or absent. The highlighting of the micro-organisms in question requires urgent complementary investigations: hemocultures, bronchiolo-alveolar washing. In certain cases, it will be possible to resort to the transtracheal puncture or transthoracic puncture guided by tomodensitometry, and if necessary to pulmonary biopsy under videothoracoscopy. Emergency of the anti

  10. Liver-stage malaria parasites vulnerable to diverse chemical scaffolds

    PubMed Central

    Derbyshire, Emily R.; Prudêncio, Miguel; Mota, Maria M.; Clardy, Jon

    2012-01-01

    Human malaria infection begins with a one-time asymptomatic liver stage followed by a cyclic symptomatic blood stage. All high-throughput malaria drug discovery efforts have focused on the cyclic blood stage, which has limited potential for the prophylaxis, transmission blocking, and eradication efforts that will be needed in the future. To address these unmet needs, a high-throughput phenotypic liver-stage Plasmodium parasite screen was developed to systematically identify molecules with liver-stage efficacy. The screen recapitulates liver-stage infection by isolating luciferase-expressing Plasmodium berghei parasites directly from the salivary glands of infected mosquitoes, adding them to confluent human liver cells in 384-well plates, and measuring luciferase activity after a suitable incubation period. Screening 5,375 known bioactive compounds identified 37 liver-stage malaria inhibitors with diverse modes of action, as shown by inhibition time course experiments. Further analysis of the hits in the Food and Drug Administration-approved drug subset revealed compounds that seem to act specifically on the liver stage of infection, suggesting that this phase of the parasite’s life cycle presents a promising area for new drug discovery. Notably, many active compounds in this screen have molecular structures and putative targets distinctly different from those of known antimalarial agents. PMID:22586124

  11. Multiple stage railgun

    SciTech Connect

    Aaland, K.; Hawke, R.S.; Scudder, J.K.

    1982-08-10

    A multiple stage magnetic railgun accelerator for accelerating a projectile by movement of a plasma arc along the rails. The railgun is divided into a plurality of successive rail stages which are sequentially energized by separate energy sources as the projectile moves through the bore of the railgun. Propagation of energy from an energized rail stage back towards the breech end of the railgun can be prevented by connection of the energy sources to the rails through isolation diodes. Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails into electrically isolated rail sections. In such case means are used to extinguish the arc at the end of each energized stage and a fuse or laser device is used to initiate a new plasma arc in the next energized rail stage.

  12. Two-stage Supercharging

    NASA Technical Reports Server (NTRS)

    Buck, Richard S

    1941-01-01

    The arrangement of the parts and the installation and control problems of the two-stage mechanically driven superchargers for aircraft engines are discussed. Unless an entirely new form of supercharging is developed, there will be a definite need for a two-stage centrifugal supercharger. It is shown that the two-stage mechanically driven supercharger itself is a comparatively simple device; the complications arise from the addition of inter-coolers and controls.

  13. Canine rickettsial infections.

    PubMed

    Stiles, J

    2000-09-01

    Dogs that live in tick-infested areas are at risk for contracting rickettsial infections. Clinical signs associated with ehrlichiosis or Rocky Mountain spotted fever may be dramatic or mild. Clinicians must consider the possibility of rickettsial diseases to request laboratory tests that will permit a proper diagnosis. Specific antimicrobial therapy usually brings about clinical improvement, although some dogs may not be cleared of rickettsial organisms, even with prolonged treatment. A small percentage of dogs die of rickettsial infections, either in the acute stage or owing to chronic bone marrow suppression and generalized debilitation. Ocular lesions are an important clinical sign in canine rickettsial infections and may aid the clinician in making a diagnosis and monitoring response to therapy. PMID:11033879

  14. TORCH infections.

    PubMed

    Neu, Natalie; Duchon, Jennifer; Zachariah, Philip

    2015-03-01

    TORCH infections classically comprise toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus, hepatitis viruses, human immunodeficiency virus, and other infections, such as varicella, parvovirus B19, and enteroviruses. The epidemiology of these infections varies; in low-income and middle-income countries, TORCH infections are major contributors to prenatal, perinatal, and postnatal morbidity and mortality. Evidence of infection may be seen at birth, in infancy, or years later. For many of these pathogens, treatment or prevention strategies are available. Early recognition, including prenatal screening, is key. This article covers toxoplasmosis, parvovirus B19, syphilis, rubella, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. PMID:25677998

  15. Heterologous Infection During Chagas' Disease

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Cossi Isasi, S.

    2007-05-01

    Human populations are often infected with more than one parasite strain. This is frequently the case with ChagasŠ disease, which is endemic to large regions of Latin America. In the present work we study the dynamics of the heterologous infection for this disease, using a model for the interaction between the trypanosoma cruzi parasite and the immune system. We find the dependence of the nature of the post-acute stage on the parameters characterizing the inoculated infectious strains.

  16. Sarcocystis spp. in human infections.

    PubMed

    Fayer, Ronald

    2004-10-01

    Sarcocystis species are intracellular protozoan parasites with an intermediate-definitive host life cycle based on a prey-predator relationship. Asexual stages develop in intermediate hosts after they ingest the oocyst stage from definitive-host feces and terminate with the formation of intramuscular cysts (sarcocysts). Sarcocysts in meat eaten by a definitive host initiate sexual stages in the intestine that terminate in oocysts excreted in the feces. Most Sarcocystis species infect specific hosts or closely related host species. For example, humans and some primates are definitive hosts for Sarcocystis hominis and S. suihominis after eating raw meat from cattle and pigs, respectively. The prevalence of intestinal sarcocystosis in humans is low and is only rarely associated with illness, except in volunteers who ingest large numbers of sarcocysts. Cases of infection of humans as intermediate hosts, with intramuscular cysts, number less than 100 and are of unknown origin. The asexual stages, including sarcocysts, can stimulate a strong inflammatory response. Livestock have suffered acute debilitating infections, resulting in abortion and death or chronic infections with failure to grow or thrive. This review provides a summary of Sarcocystis biology, including its morphology, life cycle, host specificity, prevalence, diagnosis, treatment, and prevention strategies, for human and food animal infections. PMID:15489353

  17. Sarcocystis spp. in Human Infections

    PubMed Central

    Fayer, Ronald

    2004-01-01

    Sarcocystis species are intracellular protozoan parasites with an intermediate-definitive host life cycle based on a prey-predator relationship. Asexual stages develop in intermediate hosts after they ingest the oocyst stage from definitive-host feces and terminate with the formation of intramuscular cysts (sarcocysts). Sarcocysts in meat eaten by a definitive host initiate sexual stages in the intestine that terminate in oocysts excreted in the feces. Most Sarcocystis species infect specific hosts or closely related host species. For example, humans and some primates are definitive hosts for Sarcocystis hominis and S. suihominis after eating raw meat from cattle and pigs, respectively. The prevalence of intestinal sarcocystosis in humans is low and is only rarely associated with illness, except in volunteers who ingest large numbers of sarcocysts. Cases of infection of humans as intermediate hosts, with intramuscular cysts, number less than 100 and are of unknown origin. The asexual stages, including sarcocysts, can stimulate a strong inflammatory response. Livestock have suffered acute debilitating infections, resulting in abortion and death or chronic infections with failure to grow or thrive. This review provides a summary of Sarcocystis biology, including its morphology, life cycle, host specificity, prevalence, diagnosis, treatment, and prevention strategies, for human and food animal infections. PMID:15489353

  18. MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

    ClinicalTrials.gov

    2015-03-16

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  19. "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…

  20. Determination of genomic DNA sequences for beta-tubulin isotype 1 from multiple species of cyathostomin and detection of resistance alleles in third-stage larvae from horses with naturally acquired infections

    PubMed Central

    Lake, Sarah L; Matthews, Jacqueline B; Kaplan, Ray M; Hodgkinson, Jane E

    2009-01-01

    Background Genetic resistance against benzimidazole (BZ) anthelmintics is widespread in cyathostomins, the commonest group of intestinal parasitic nematodes of horses. Studies of BZ-resistant nematodes of sheep, particularly Haemonchus contortus, have indicated that an anthelmintic resistance-conferring T/A polymorphism, encoding an F (phenylalanine) to Y (tyrosine) substitution, in beta-tubulin isotype 1 is present at two loci, codons 167 and 200 (F167Y, F200Y). Recent studies using complementary (c) DNA derived from BZ-susceptible and -resistant cyathostomins identified statistical differences in the frequency of the BZ-resistant A allele at these loci. However, the lack of high-throughput genomic DNA-based detection of polymorphisms limits the study of eggs or larvae from field isolates. In the present study, we report genomic DNA sequences for beta-tubulin isotype 1 from multiple cyathostomin species, thus facilitating the development of pyrosequencing assays to genetically characterize third-stage larvae (L3s) of cyathostomins from mixed-species field isolates. Results Sequence analysis of the beta-tubulin isotype 1 gene in a common species, Cylicocyclus nassatus, indicates a revised genomic structure to published data, revealing that codons 167 and 200 are located on separate exons. A consensus sequence was generated from 91 and 76 individual cyathostomins for the regions spanning codons 167 and 200, respectively. A multi-species genomic DNA-based assay was established to directly pyrosequence individual L3 from field samples of unknown species and BZ sensitivity in a 96-well plate. In this format, the assay to detect F167Y gave a 50-90% success rate. The optimisation of the assay at codon 200 is currently underway. Subsequently, the genotype at F167Y was determined for 241 L3s, collected prior to and after BZ treatment. These results demonstrated a reduction in the heterozygous genotype, TTC/TAC, and an increase in the homozygous resistant genotype TAC

  1. Yellow Fever Virus Infection

    PubMed Central

    David-West, Tam. S.; Smith, J. A.

    1971-01-01

    A sequential and quantitative survey of brain and liver of suckling mice for infective virus and complement-fixing antigen, after infection with yellow fever virus, showed that while there was progressive increase of infective virus content in both organs, only the brain showed a corresponding rise in CF antigen. Histopathological examination revealed that the liver was not significantly involved. The target organ was the brain, where the progressive pathological changes culminated in an acute encephalitis by the 3rd day of experiment. Organ destruction began with the molecular layer of the grey matter. But by the 4th day after infection the entire cerebral cortex was involved. At the initial stages the hippocampus was particularly affected. Tissue damage did not appear to be entirely due to the differential quantitative localization of infective virus. It was hypothesized that the CF antigen acting singly or in conjunction with some hypothetical proteins may be principally involved in the pathological outcome of the disease. ImagesFigs. 7-9Figs. 3-6 PMID:5582071

  2. Norovirus Infection

    MedlinePlus

    ... About NIAID News & Events Volunteer NIAID > Health & Research Topics > Norovirus Infection Skip Website Tools Website Tools Print this page Get email updates Order publications Volunteer for Clinical ...

  3. Imaging infection.

    PubMed

    Ketai, Loren; Jordan, Kirk; Busby, Katrina H

    2015-06-01

    Thoracic imaging is widely used to detect lower respiratory tract infections, identify their complications, and aid in differentiating infectious from noninfectious thoracic disease. Less commonly, the combination of imaging findings and a clinical setting can favor infection with a specific organism. This confluence can occur in cases of bronchiectatic nontuberculous mycobacterial infections in immune-competent hosts, invasive fungal disease among neutropenic patients, Pneumocystis jiroveci pneumonia in patients with AIDS, and in cytomegalovirus infections in patients with recent hematopoietic cell transplantation. These specific diagnoses often depend on computed tomography scanning rather than chest radiography alone. PMID:26024600

  4. Centaur upper stage

    NASA Astrophysics Data System (ADS)

    Groesbeck, W.

    An account is given of the design features of the LOX/LH2-fueled Centaur upper stage engine and fuel cryotankage, in order to serve as a basis for understanding the Main Engine Cut Off (MECO) system instituted. MECO follows the instant of spacecraft separation from the upper stage. The planetary launch program during 1966-1978 involved 23 Centaur launches and led to no upper stage reentry; LEO missions for HEAO and OAO satellite lofting in 1963-1979 involved nine Centaur launches and led to five reentries. GEO satellite launches in 1969-1986 saw 32 launches and three known reentries.

  5. Prostate cancer staging

    MedlinePlus

    ... effects of treatment The chance that treatment can cure your cancer or help you in other ways With stage ... III prostate cancer, the main goal is to cure the cancer by treating it and keeping it from coming ...

  6. 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 ...

  7. Stages of Pregnancy

    MedlinePlus

    ... your baby in these three stages. First trimester (week 1-week 12) First trimester See how your baby is ... is each pregnancy. Return to top Second trimester (week 13-week 28) Second trimester See how your ...

  8. 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.

  9. 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.

  10. Understanding cancer staging

    MedlinePlus

    ... the body. The spread of cancer is called metastasis . Cancer staging is used to help describe the ... cancer has spread to nearby lymph nodes (N) Metastasis (M) , or if and how much the cancer ...

  11. 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

  12. 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.

  13. 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.

  14. Postpartum Infections

    MedlinePlus

    ... Drug Interactions Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News ... Muscle Disorders Brain, Spinal Cord, and Nerve Disorders Cancer Children's Health Issues ... Bladder and Kidney Infections Breast Infection Postpartum Blood Clots Postpartum Thyroid Disorders Postpartum ...

  15. Norovirus Infections

    MedlinePlus

    ... include fever, headache or body aches. Treatment includes bed rest and lots of liquids to prevent dehydration. There is no specific medicine to treat norovirus infections. Proper hand washing and safe food preparation may help prevent infections. Centers for Disease Control and Prevention

  16. Bone Infections

    MedlinePlus

    ... 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 fever Swelling, warmth, and redness A blood ...

  17. Mycobacterial Infections

    MedlinePlus

    ... similar to tuberculosis: Cough Weight loss Coughing up blood or mucus Weakness or fatigue Fever and chills Night sweats Lack of appetite and weight loss Medicines can treat these infections, but often more than one is needed to cure the infection.

  18. Salmonella Infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bacteria of the genus Salmonella are responsible for a variety of acute and chronic diseases in poultry. These diseases continue to cause economically significant losses in many nations and absorb a large investment of resources in testing and control efforts in others. Infected poul...

  19. Infection of Plasmodiophora brassicae in Chinese cabbage.

    PubMed

    Ji, R; Zhao, L; Xing, M; Shen, X; Bi, Q; Peng, S; Feng, H

    2014-01-01

    Brassica crops infected by Plasmodiophora brassicae can produce root galls (clubroots) and be prevented from growing normally. To understand the series of changes that occur in the host root during root gall production, the resistance character of 21 Chinese cabbage lines were identified and then resistant and susceptible lines were used for infection observation. Hydroponic technology system was used for plants growing, and the infection process of P. brassicae in the roots of resistant and susceptible Chinese cabbage was examined based on morphology and microscopic characteristics using micoscope. In susceptible Chinese cabbage, the root hair infection stage occurred over approximately 7 days after inoculation, the cortical infection happened over approximatly 14 days after inoculation, and clubroots formed in approximately 30 days after inoculation. However, in resistant Chinese cabbage, the pathogen could be prevented and maintained in the root hair infection stage. This research provides a foundation for the subsequent studies of cabbage resistance of P. brassicae. PMID:25526218

  20. 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

  1. Public Opinion, Public Policy, and HIV Infection.

    ERIC Educational Resources Information Center

    West, Jane

    1989-01-01

    A four-stage framework for considering the development of public policy in regard to the issue of HIV (Human Immunodeficiency Virus) infection is offered. The phases are denial, irrationality, acceptance, and the development of a rational response. Federal antidiscrimination policies which include persons with HIV infections as disabled are…

  2. 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.

  3. Refractory Arthrographis kalrae native knee joint infection

    PubMed Central

    Boan, Peter; Arthur, Ian; Golledge, Clay; Ellis, David

    2012-01-01

    Rare reports of infection with Arthrographis kalrae have often demonstrated a protracted clinical course. We describe refractory infection of the native knee with Arthrographis kalrae after a penetrating injury and Yttrium synovectomy, finally controlled with two stage joint revision and combination antifungal therapy. The paucity of worldwide data about such uncommon invasive fungal infections contributes to the diagnostic and therapeutic challenges of these cases. PMID:24371754

  4. Photoacoustic spectroscopy of man infecting protozoans

    NASA Astrophysics Data System (ADS)

    Acosta-Avalos, D.; Alvarado-Gil, J. J.; Vargas, H.

    1998-08-01

    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.

  5. Principles of Melanoma Staging.

    PubMed

    Boland, Genevieve M; Gershenwald, Jeffrey E

    2016-01-01

    Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging. PMID:26601861

  6. One-stage vs. three-stage repair in anorectal malformation with rectovestibular fistula

    PubMed Central

    Amanollahi, Omid; Ketabchian, Saman

    2016-01-01

    Background: Anorectal malformations (ARMs) disease is one of the congenital anomalies with an incidence of about 1 in 5000 neonate births, and treatment requires surgical intervention. Selecting the one- or three-step surgical procedure to treat the disease, especially in female neonates with rectovestibular fistula, is a subject of debate. This study aims to compare the advantages and disadvantages of these two methods. Materials and Methods: Forty female neonates with ARM and rectovestibular fistula between March 2011 and March 2013 were included in the study, and they were divided into two equal groups. Allocation of the first case was random, and all cases were then allocated alternatively (every other subject was assigned to a treatment group) until each group received 20 cases equally patients of study group underwent a one-stage posterior sagittal anorectoplasty (PSARP) and in control group patients underwent a three-stage operation (colostomy, PSARP, and closure of colostomy). The complications during and after the surgery were recorded in both groups, and the results were compared. Results: In the control group, only one case (5%) of wound infection and dehiscence was seen, whereas in the one-stage study group, six cases (30%) of wound infection and dehiscence were seen (P value = 0.046). However, regarding the incidence of other complications, such as iatrogenic vaginal injury as well as final recovery, no considerable differences were seen between the two groups. Conclusions: Despite more surgical site infections and dehiscence in the one-stage repair, but due to the numerous advantages compared to the three-stage method, which is more time-consuming, more costly, and causes more adverse effect on parents and children, performing the one-stage repair is recommended for this anomaly. PMID:27251519

  7. New School Stages for Old.

    ERIC Educational Resources Information Center

    Miller, James Hull

    A new and dynamic approach to auditorium stage design is presented. Contents include--(1) modified proscenium stage plan--a definition, (2) benefits of a modified proscenium stage plan, and (3) details of a modified proscenium stage plan--basic concepts, a typical layout, projection systems, and scenic design for space stage. (RH)

  8. 2-Stage Classification Modeling

    Energy Science and Technology Software Center (ESTSC)

    1994-11-01

    CIRCUIT2.4 is used to design optimum two-stage classification configurations and operating conditions for energy conservation. It permits simulation of five basic grinding-classification circuits, including one single-stage and four two-stage classification arrangements. Hydrocyclones, spiral classifiers, and sieve band screens can be simulated, and the user may choose the combination of devices for the flowsheet simulation. In addition, the user may select from four classification modeling methods to achieve the goals of a simulation project using themore » most familiar concepts. Circuit performance is modeled based on classification parameters or equipment operating conditions. A modular approach was taken in designing the program, which allows future addition of other models with relatively minor changes.« less

  9. 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. PMID:27486731

  10. Solid organ transplantation and HIV infection.

    PubMed

    Polak, Wojciech G; Gładysz, Andrzej

    2003-01-01

    HIV infection has been traditionally considered to be an absolute contraindication for solid organ transplantation. Recent advances in HIV treatment, as highly active antiretroviral therapy (HAART), significantly reduced HIV-related mortality and morbidity. At the same time the number of HIV-infected patients with end-stage organ diseases constantly increased. Current data describing solid organ transplantation in HIV-infected patients demonstrated comparable outcome to that in the HIV-negative population. In light of this, solid organ transplantation should be considered as a treatment option for selected HIV-positive patients with end-stage organ disease. PMID:15171000

  11. Stage cementing apparatus

    SciTech Connect

    Blamford, D.M.; Easter, J.H.

    1988-06-21

    A stage cementing apparatus for selectively passing cement from the interior passage of a casing to the annulus between the exterior of the casing and borehole, the casing having an upper portion and a lower portion, is described comprising: a barrel secured to the upper portion of the casing; a mandrel secured to the lower portion of the casing, and a stage cementing tool having a generally cylindrical configuration adapted for attachment to the lower end of the barrel about a portion of the mandrel.

  12. 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.

  13. Whipworm infection

    MedlinePlus

    ... Images Trichuris trichiura egg References Diemert DJ. Intestinal nematode infections. In: Goldman L, Schafer AI, eds. Goldman's ... Elsevier Saunders; 2011:chap 365. Maguire JH. Intestinal nematodes (roundworms). In: Mandell GL, Bennett JE, Dolin R, ...

  14. Hantavirus Infections

    MedlinePlus

    ... breathe infected air or come into contact with rodents or their urine or droppings. You cannot catch ... symptoms include coughing and shortness of breath. Controlling rodents in and around your house is the best ...

  15. Ear Infections

    MedlinePlus

    MENU Return to Web version Ear Infections Overview How does the ear work? A tube called the eustachian (say: "you-stay-shee-an") tube connects the middle ear with the back of the nose. Normally this ...

  16. 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 ...

  17. Skin Infections

    MedlinePlus

    ... nearby What to Do Teach kids not to pop, pick at, or scratch pimples, pus-filled infections, ... Your Skin Abscess Impetigo Ringworm Cellulitis Should I Pop My Pimple? Tips for Taking Care of Your ...

  18. Campylobacter infection

    MedlinePlus

    ... with suspected enteric infection. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 24th ed. Philadelphia, PA: ... with diarrhea and malabsorption. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 24th ed. Philadelphia, PA: ...

  19. Giardia infection

    MedlinePlus

    ... with suspected enteric infection. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... with diarrhea and malabsorption. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  20. Staphylococcal Infections

    MedlinePlus

    ... number of skin infections (eg, impetigo, pimples, boils). Staphylococcus aureus also causes toxin-related illnesses, including toxic shock syndrome, scalded skin syndrome, and staphylococcal-related food poisoning. In fact, ... Staphylococcus that you should be familiar with include the ...

  1. 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 ...

  2. Pneumococcal Infections

    MedlinePlus

    ... blood, imaging, or lab tests. Treatment is with antibiotics. Vaccines can prevent pneumococcal infections. There are two vaccines. One is for infants and young children. The other is for people ...

  3. Salmonella Infections

    MedlinePlus

    ... vegetables. You also can get infected after handling pets, especially reptiles like snakes, turtles, and lizards. Symptoms include Fever Diarrhea Abdominal cramps Headache Possible nausea, vomiting, and loss of appetite Symptoms usually last 4-7 days. ...

  4. 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

  5. Norovirus Infections

    MedlinePlus

    Noroviruses are a group of related viruses. Infection with these viruses causes an illness called gastroenteritis, an inflammation of the stomach and intestines. It can spread from person to person, or ...

  6. 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…

  7. "Stage 40" Handbook.

    ERIC Educational Resources Information Center

    Mill River Union High School, North Clarendon, VT.

    The policies, purposes, and guidelines of "Stage 40," an educational repertory company for students, are presented in this paper, which also explains how the company functions. The paper discusses the company's history, the relationship between the company and academics, and the responsibilities of a company member. Letters by the board members…

  8. The Scribble Stage

    ERIC Educational Resources Information Center

    Douglas, Katherine

    2012-01-01

    The term "Scribble Stage" highlights how first efforts appear in student independent work. Age does not correlate with "scribble" work as does experience; upper grade students and even adults will often approach new materials and techniques in an experimental manner as a means to become familiar with them. Everyone is a beginner at the things they…

  9. 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…

  10. 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. ...

  11. 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.

  12. 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.

  13. Evolutive leukoencephalopathy in congenital cytomegalovirus infection.

    PubMed

    Krakar, Goran; Đaković, Ivana; Delin, Sanja; Bošnjak, Vlatka Mejaški

    2015-01-01

    Congenital cytomegalovirus infection is the most common infectious cause of congenital brain injury. Type and severity of congenital cytomegalovirus infection-related brain abnormalities depend on the developmental stage of the central nervous system at the time of fetal infection. The aim of this study was to follow the course of leukoencephalopathy in a patient with congenital cytomegalovirus infection. We describe brain magnetic resonance imaging (MRI) findings of a boy with symptomatic congenital cytomegalovirus infection performed at the age of 3 weeks, 13 months, and 4 and 7 years. Neonatal brain MRI showed most of characteristic findings in congenital cytomegalovirus infection with most prominent white matter abnormalities and cortical dysplasia. MRI follow-up images showed that cortical dysgenesis remained unchanged and static, whereas white matter abnormalities evolved over the years. We propose that leukoencephalopathy in congenital cytomegalovirus infection is not only nonprogressive or static but even evolutive and suggests both underlying disruption and delay of myelination. PMID:24453153

  14. Pinworm Infection

    MedlinePlus

    ... the pinworm—egg, larva (immature stage), and mature worm—takes place inside the human body and requires ... barely noticeable. The movement of egg-laden female worms from your anus to deposit their eggs will ...

  15. Genes expressed in grapevine leaves reveal latent wood infection by the fungal pathogen Neofusicoccum parvum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Detection of wood-infecting pathogens is often limited to the late stage of infection, when disease symptoms are obvious. Detection of the early stage of infection would benefit from identification of host-based markers in asymptomatic leaves. The fungus Neofusicoccum parvum (Botryosphaeria diebac...

  16. MICE Staging and Status

    SciTech Connect

    Hanlet, Pierrick

    2010-03-30

    Ionization cooling will be a key technique for a high-intensity Neutrino Factory or Muon Collider. The Muon Ionization Cooling Experiment (MICE) is a high-precision, staged accelerator experiment being performed at Rutherford Appleton Laboratory in the UK. Its goal is the first demonstration, with 0.1% resolution, of the feasibility of reducing the transverse emittance of a beam of muons by ionization cooling in low-Z absorbers. MICE is being staged in the following steps: I. Creating and characterizing a beam of muons; II. Measuring their emittance; III. Systematic comparison of successive measurements; IV. Inserting absorber; V. Reaccelerating longitudinally; and VI. Complete '10%-cooling' test. Step I is currently in progress with Step II to commence next year; completion of Step VI is anticipated in approx2012.

  17. MICE Staging and Status

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick

    2010-03-01

    Ionization cooling will be a key technique for a high-intensity Neutrino Factory or Muon Collider. The Muon Ionization Cooling Experiment (MICE) is a high-precision, staged accelerator experiment being performed at Rutherford Appleton Laboratory in the UK. Its goal is the first demonstration, with 0.1% resolution, of the feasibility of reducing the transverse emittance of a beam of muons by ionization cooling in low-Z absorbers. MICE is being staged in the following steps: I. Creating and characterizing a beam of muons; II. Measuring their emittance; III. Systematic comparison of successive measurements; IV. Inserting absorber; V. Reaccelerating longitudinally; and VI. Complete "10%-cooling" test. Step I is currently in progress with Step II to commence next year; completion of Step VI is anticipated in ˜2012.

  18. 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

  19. 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

  20. Staged Event Architecture

    Energy Science and Technology Software Center (ESTSC)

    2005-05-30

    Sea is a framework for a Staged Event Architecture, designed around non-blocking asynchronous communication facilities that are decoupled from the threading model chosen by any given application, Components for P networking and in-memory communication are provided. The Sea Java library encapsulates these concepts. Sea is used to easily build efficient and flexible low-level network clients and servers, and in particular as a basic communication substrate for Peer-to-Peer applications.

  1. Endometrial carcinoma stage I.

    PubMed

    Baram, A; Ron, I; Kupferminc, M; Inbar, M

    1997-01-01

    Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately. PMID:21590195

  2. Cytomegalovirus infection.

    PubMed

    Climent, C; Vélez, R; Capriles, J A

    1992-01-01

    Post-transfusion CMV infection most frequently results in asymptomatic seroconversion. Among immunocompetent patients only seronegative pregnant women require such products because of the risk of fetal CMV infection. In selected groups of immunocompromised patients, significant disease can occur. It is desirable to provide blood and blood components with reduced CMV risk to the following patients: seronegative infants weighting less than 1200 g at birth, seronegative bone marrow transplant patients who receive marrow from seronegative donors and seronegative renal transplant patients receiving kidneys from seronegative donors. Heart and liver transplantation seronegative patients may receive seronegative blood if the donor is seronegative. CMV--seronegative HIV infected cases may also be transfused with CMV--seronegative blood. PMID:1323967

  3. [Legionella infections].

    PubMed

    Fleurette, J

    1983-01-01

    The authors review the bacteriological features of Legionella infections, their clinical symptoms and the methods of diagnosis. They stress the unusual ecological features of Legionella which generally lives in natural water reservoirs or in artificial reservoirs (drinking water piping, air conditioning). In the clinical situation, current emphasis is on the extrapulmonary infections whose pathogenesis has not yet been fully explained. The incidence and prevalence of Legionella in pneumonia still needs to be defined. The methods of bacteriological and serological diagnosis are described as well as the ways of interpreting the results. PMID:6666882

  4. 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

  5. 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.

  6. 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

  7. Endemic infection reduces transmission potential of an epidemic parasite during co-infection.

    PubMed

    Randall, J; Cable, J; Guschina, I A; Harwood, J L; Lello, J

    2013-10-22

    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

  8. Whole organism blood stage vaccines against malaria.

    PubMed

    Stanisic, Danielle I; Good, Michael F

    2015-12-22

    Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in significant morbidity and mortality worldwide. An effective malaria vaccine is considered by many to be the definitive solution. Yet, after decades of research, we are still without a vaccine that is capable of inducing robust, long lasting protection in naturally exposed individuals. Extensive sub-unit vaccine development focused on the blood stage of the malaria parasite has thus far yielded disappointing results. There is now a renewed focus on whole parasite vaccine strategies, particularly as they may overcome some of the inherent weaknesses deemed to be associated with the sub-unit approach. This review discusses the whole parasite vaccine strategy focusing on the blood stage of the malaria parasite, with an emphasis on recent advances and challenges in the development of killed and live attenuated vaccines. PMID:26428451

  9. HIV infection and lymphoma

    PubMed Central

    Grogg, K L; Miller, R F; Dogan, A

    2007-01-01

    The incidence of lymphoma in patients with HIV infection greatly exceeds that of the general population. The increased risk for lymphoma appears related to multiple factors, including the transforming properties of the retrovirus itself, the immunosuppression and cytokine dysregulation that results from the disease, and, most importantly, opportunistic infections with other lymphotrophic herpes viruses such as Epstein–Barr virus and human herpesvirus 8. Histologically lymphomas fall into three groups: (1) those also occurring in immunocompetent patients; (2) those occurring more specifically in HIV‐positive patients; and (3) those also occurring in patients with other forms of immunosuppression. Aggressive lymphomas account for the vast majority cases. They frequently present with advanced stage, bulky disease with high tumour burden and, typically, involve extranodal sites. Clinical outcome appears to be worse than in similar aggressive lymphomas in the general population. However, following the introduction of highly active antiretroviral therapy, the risk for developing lymphoma in the context of HIV infection has decreased and the clinical outcome has improved. PMID:18042692

  10. Modeling the Dynamics of Plasmodium vivax Infection and Hypnozoite Reactivation In Vivo

    PubMed Central

    Adekunle, Adeshina I.; Pinkevych, Mykola; McGready, Rose; Luxemburger, Christine; White, Lisa J.; Nosten, François; Cromer, Deborah; Davenport, Miles P.

    2015-01-01

    The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90–96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG. PMID:25780913

  11. 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 ...

  12. Paratyphoid Infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The numerous motile Salmonella serotypes are often referred to collectively as paratyphoid (PT) salmonellae. Found throughout the world, these organisms can infect a very wide variety of hosts (including invertebrate and vertebrate wildlife, domestic animals, and humans) to yield either asymptomati...

  13. 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...

  14. Campylobacter Infections

    MedlinePlus

    ... Campylobacter is found in the intestines of many wild and domestic animals. The bacteria are passed in their feces (poop), which can lead to infection in humans via contaminated food, meats (especially chicken), water taken from contaminated sources (streams or rivers ...

  15. Giardia Infections

    MedlinePlus

    ... diagnose it. You often need to collect several samples to test. Doctors use several drugs to treat it. The best way to prevent giardia infection is to practice good hygiene, including frequent hand washing. You should not drink water that may be contaminated. You should also peel ...

  16. 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 ...

  17. Streptococcal Infections

    MedlinePlus

    ... Strep throat - a sore, red throat, sometimes with white spots on the tonsils Scarlet fever - an illness that follows strep throat. It causes a red rash on the body. Impetigo - a skin infection Toxic shock syndrome Cellulitis and necrotizing fasciitis (flesh-eating disease) Group ...

  18. 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 ...

  19. Fusarium Infection

    PubMed Central

    Muhammed, Maged; Anagnostou, Theodora; Desalermos, Athanasios; Kourkoumpetis, Themistoklis K.; Carneiro, Herman A.; Glavis-Bloom, Justin; Coleman, Jeffrey J.

    2013-01-01

    Abstract Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested. PMID:24145697

  20. Treatment Options by Stage (Anal Cancer)

    MedlinePlus

    ... following stages are used for anal cancer: Stage 0 (Carcinoma in Situ) In stage 0 , abnormal cells ... or check-ups. Treatment Options by Stage Stage 0 (Carcinoma in Situ) Treatment of stage 0 is ...

  1. Craniotomy infections.

    PubMed

    Blomstedt, G C

    1992-04-01

    The incidence of craniotomy infections, usually less than 5%, is dependent on many factors, such as how the information is collected and how the percentage is calculated. Because these factors may vary from report to report, incidence figures should be read with skepticism. It is difficult to prove that a given factor contributes to infection. Most routines are based more on personal convictions than on solid evidence. CSF leak is one factor known to have great impact; it should be avoided with painstaking technique and, if it occurs, it should be treated promptly. Solid evidence favoring prophylactic antibiotics for persistent CSF leak is not available; but, until a well-designed randomized study tells otherwise, the high risk of meningitis justifies prophylaxis. Penicillin is adequate for leaks through the nose or the ear. For leaks through the skin, the antibiotic should be effective against staphylococci. The infection register should provide information about prevailing bacteria. In many hospitals, the prophylaxis should cover gram-negative bacilli. CRP is a useful diagnostic aid for detecting postoperative infections. The operation, however, also causes a CRP rise. Daily CRP monitoring, at least for patients with elevated temperature, is recommended. The third-generation cephalosporins are a welcome contribution to the treatment of bacterial meningitis. To avoid side effects, and to keep them potent when they are really needed, they should be used with caution. Most postoperative cases of meningitis are in fact aseptic. If the patient is moderately ill, chloramphenicol is still eligible as the first choice antibiotic. When the bacterial culture is negative, the antibiotic should be stopped. The standard treatment for bone flap infection is removal of the bone flap. The bone flap is essentially devascularized and comparable to a foreign body. The justification of vancomycin prophylaxis has been shown in a randomized study. PMID:1633466

  2. 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.

  3. 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.

  4. Early Diagnosis and Staging.

    PubMed

    Lilja, H; Lilja, D R H

    1999-01-01

    This report reviews developments in the early diagnosis and staging of prostate cancer and updated on the incidence of postate cancer to discuss the pros and cons of population based screening. Refinements and reliability of various diagnosic procedures are described such as PSA testing, transrectal ultrasound, ratio beteen PSA-level and ultrasound measured prostate volume, rate of change of PSA-level, combination factor equations computed by neural network programs to predict likelihood of prostate cancer, artificial neural network analysis of subvisual transrectal ultrasound information, measurements of different PSA-forms of PSA (in particular percent free PSA), and glandular kallikrein 2. PMID:12496851

  5. 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.

  6. Revision of infected knee arthroplasties in Denmark.

    PubMed

    Lindberg-Larsen, Martin; Jørgensen, Christoffer C; Bagger, Jens; Schrøder, Henrik M; Kehlet, Henrik

    2016-08-01

    Background and purpose - The surgical treatment of periprosthetic knee infection is generally either a partial revision procedure (open debridement and exchange of the tibial insert) or a 2-stage exchange arthroplasty procedure. We describe the failure rates of these procedures on a nationwide basis. Patients and methods - 105 partial revisions (100 patients) and 215 potential 2-stage revision procedures (205 patients) performed due to infection from July 1, 2011 to June 30, 2013 were identified from the Danish Knee Arthroplasty Register (DKR). Failure was defined as surgically related death ≤ 90 days postoperatively, re-revision due to infection, or not reaching the second stage for a planned 2-stage procedure within a median follow-up period of 3.2 (2.2-4.2) years. Results - The failure rate of the partial revisions was 43%. 71 of the partial revisions (67%) were revisions of a primary prosthesis with a re-revision rate due to infection of 34%, as compared to 55% in revisions of a revision prosthesis (p = 0.05). The failure rate of the 2-stage revisions was 30%. Median time interval between stages was 84 (9-597) days. 117 (54%) of the 2-stage revisions were revisions of a primary prosthesis with a re-revision rate due to infection of 21%, as compared to 29% in revisions of a previously revised prosthesis (p = 0.1). Overall postoperative mortality was 0.6% in high-volume centers (> 30 procedures within 2 years) as opposed to 7% in the remaining centers (p = 0.003). Interpretation - The failure rates of 43% after the partial revision procedures and 30% after the 2-stage revisions in combination with the higher mortality outside high-volume centers call for centralization and reconsideration of surgical strategies. PMID:26900908

  7. 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

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed 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 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

  8. Plasmodium vivax trophozoite-stage proteomes

    PubMed Central

    Anderson, D.C.; Lapp, Stacey A.; Akinyi, Sheila; Meyer, Esmeralda V.S.; Barnwell, John W.; Korir-Morrison, Cindy; Galinski, Mary R.

    2015-01-01

    Plasmodium vivax is the causative infectious agent of 80–300 million annual cases of malaria. Many aspects of this parasite’s biology remain unknown. To further elucidate the interaction of P. vivax with its Saimiri boliviensis host, we obtained detailed proteomes of infected red blood cells, representing the trophozoite-enriched stage of development. Data from two of three biological replicate proteomes, emphasized here, were analyzed using five search engines, which enhanced identifications and resulted in the most comprehensive P. vivax proteomes to date, with 1375 P. vivax and 3209 S. boliviensis identified proteins. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with P. vivax’s known reticulocyte host–cell specificity. A majority of the host and pathogen proteins identified belong to specific functional categories, and several parasite gene families, while 33% of the P. vivax proteins have no reported function. Hemoglobin was significantly oxidized in both proteomes, and additional protein oxidation and nitration was detected in one of the two proteomes. Detailed analyses of these post-translational modifications are presented. The proteins identified here significantly expand the known P. vivax proteome and complexity of available host protein functionality underlying the host–parasite interactive biology, and reveal unsuspected oxidative modifications that may impact protein function. Biological significance Plasmodium vivax malaria is a serious neglected disease, causing an estimated 80 to 300 million cases annually in 95 countries. Infection can result in significant morbidity and possible death. P. vivax, unlike the much better-studied Plasmodium falciparum species, cannot be grown in long-term culture, has a dormant form in the liver called the hypnozoite stage, has a reticulocyte host–cell preference in the blood, and creates caveolae vesicle complexes at the surface of the infected reticulocyte

  9. Pneumococcal Infections

    MedlinePlus

    ... and Stages Prenatal Baby (0-12 mos.) Toddler 1-3yrs. Preschool 3-5yrs Grade School 5-12yrs. Teen 12-18yrs. Young Adult 18-21yrs. Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & ...

  10. 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.

  11. ATTRACTION BEHAVIOR OF THREE ENTOMOPATHOGENIC NEMATODE SPECIES TOWARDS INFECTED AND UNINFECTED HOSTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Entomopathogenic nematodes bridge the gap between hosts by producing infective stage juveniles that search for, and infect, insects. Infective juveniles are likely to encounter both uninfected and already infected host insects, which will differ in their quality as a host. Here we tested the attra...

  12. DYNAMICS OF CARBON DIOXIDE RELEASE FROM INSECTS INFECTED WITH ENTOMOPATHOGENIC NEMATODES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The quality of an insect as a host to an entomopathogenic nematode infective juvenile depends in part on whether or not the insect is already infected and on the stage of that infection. Previous research has shown that nematode response to hosts can change after infection and that, for uninfected ...

  13. Immunocytochemical studies on several developmental stages of Dipetalonema viteae (Filarioidea).

    PubMed

    Prüsse, A; Vollmer, S; Diesfeld, H J

    1983-09-01

    The binding of antibodies to infective larvae (L3), eggs, uterine contents and blood microfilariae was demonstrated by light microscopy employing the peroxidase-antiperoxidase (PAP) method. Antigen-antibody reactions were located on the shell of filarial eggs as well as on the cuticle and the interior of L3 and microfilariae. Using sera from Meriones unguiculatus, Mastomys natalensis and golden hamsters infected with D. viteae obtained at 7, 14, 21 and 28 weeks p.i. it was observed that the intensity of the immunostaining on several developmental stages of the filariae decreased with increasing duration of infection. This effect was more pronounced in the case of M. unguiculatus and M. natalensis than in the case of golden hamsters. For detection of surface antigenicity the simple procedure of drying the test material on microscopic slides proved to be time saving and equally specific as compared to the embedding in Epon of the filarial stages and the successive preparation of semithin sections. However, embedded filarial stages presented more intensive immunostaining than nonembedded stages. Moreover, sections allowed to demonstrate antigen-antibody reactions on the cuticle as well as inside the body cavity of the stages. PMID:6685362

  14. 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. PMID:26341945

  15. Anthrax infection.

    PubMed

    Sweeney, Daniel A; Hicks, Caitlin W; Cui, Xizhong; Li, Yan; Eichacker, Peter Q

    2011-12-15

    Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the United States and Europe and the potential use of the bacteria for bioterrorism have focused interest on it. Furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on case series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin use, or clustering of patients with similar respiratory symptoms concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with Gram stain and culture from blood or surgical specimens followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration. PMID:21852539

  16. Anthrax Infection

    PubMed Central

    Sweeney, Daniel A.; Hicks, Caitlin W.; Cui, Xizhong; Li, Yan

    2011-01-01

    Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the United States and Europe and the potential use of the bacteria for bioterrorism have focused interest on it. Furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on case series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin use, or clustering of patients with similar respiratory symptoms concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with Gram stain and culture from blood or surgical specimens followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration. PMID:21852539

  17. 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. PMID:24365290

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. PREDICTING TURBINE STAGE PERFORMANCE

    NASA Technical Reports Server (NTRS)

    Boyle, R. J.

    1994-01-01

    This program was developed to predict turbine stage performance taking into account the effects of complex passage geometries. The method uses a quasi-3D inviscid-flow analysis iteratively coupled to calculated losses so that changes in losses result in changes in the flow distribution. In this manner the effects of both the geometry on the flow distribution and the flow distribution on losses are accounted for. The flow may be subsonic or shock-free transonic. The blade row may be fixed or rotating, and the blades may be twisted and leaned. This program has been applied to axial and radial turbines, and is helpful in the analysis of mixed flow machines. This program is a combination of the flow analysis programs MERIDL and TSONIC coupled to the boundary layer program BLAYER. The subsonic flow solution is obtained by a finite difference, stream function analysis. Transonic blade-to-blade solutions are obtained using information from the finite difference, stream function solution with a reduced flow factor. Upstream and downstream flow variables may vary from hub to shroud and provision is made to correct for loss of stagnation pressure. Boundary layer analyses are made to determine profile and end-wall friction losses. Empirical loss models are used to account for incidence, secondary flow, disc windage, and clearance losses. The total losses are then used to calculate stator, rotor, and stage efficiency. This program is written in FORTRAN IV for batch execution and has been implemented on an IBM 370/3033 under TSS with a central memory requirement of approximately 4.5 Megs of 8 bit bytes. This program was developed in 1985.

  2. Ten questions on prosthetic shoulder infection.

    PubMed

    Pinder, Elizabeth M; Ong, Joshua Cy; Bale, R Stephen; Trail, Ian A

    2016-07-01

    Prosthetic shoulder infection can cause significant morbidity secondary to pain and stiffness. Symptoms may be present for years before diagnosis because clinical signs are often absent and inflammatory markers may be normal. An emerging common culprit, Propionibacterium acnes, is hard to culture and so prolonged incubation is necessary. A negative culture result does not always exclude infection and new synovial fluid biochemical markers such as α defensin are less sensitive than for lower limb arthroplasty. A structured approach is necessary when assessing patients for prosthetic shoulder joint infection. This includes history, examination, serum inflammatory markers, plain radiology and aspiration and/or biopsy. A classification for the likelihood of prosthetic shoulder infection has been described based on culture, pre-operative and intra-operative findings. Treatment options include antibiotic suppression, debridement with component retention, one-stage revision, two-stage revision and excision arthroplasty. Revision arthroplasty is associated with the best outcomes. PMID:27583013

  3. Ten questions on prosthetic shoulder infection

    PubMed Central

    Pinder, Elizabeth M; Ong, Joshua CY; Bale, R Stephen

    2016-01-01

    Prosthetic shoulder infection can cause significant morbidity secondary to pain and stiffness. Symptoms may be present for years before diagnosis because clinical signs are often absent and inflammatory markers may be normal. An emerging common culprit, Propionibacterium acnes, is hard to culture and so prolonged incubation is necessary. A negative culture result does not always exclude infection and new synovial fluid biochemical markers such as α defensin are less sensitive than for lower limb arthroplasty. A structured approach is necessary when assessing patients for prosthetic shoulder joint infection. This includes history, examination, serum inflammatory markers, plain radiology and aspiration and/or biopsy. A classification for the likelihood of prosthetic shoulder infection has been described based on culture, pre-operative and intra-operative findings. Treatment options include antibiotic suppression, debridement with component retention, one-stage revision, two-stage revision and excision arthroplasty. Revision arthroplasty is associated with the best outcomes. PMID:27583013

  4. Staged urethroplasty: indications and techniques.

    PubMed

    Secrest, Charles L

    2002-05-01

    There is still a place for staged urethroplasty. There are some indications for staged urethral reconstruction such as strictures associated with chronic inflammation, fistula, false passage, urethral stones, urethral diverticula, abscess, failed prior repair, complicated hypospadias, severe trauma, neurologic diseases, extensive BXO strictures and long strictures. Staging a urethroplasty should not be considered a step backwards rather instead we should learn from experience and realize there are some patients who are too complex to reconstruct in a single stage. PMID:12371236

  5. Ares First Stage Element Status

    NASA Technical Reports Server (NTRS)

    Tiller, Bruce K.

    2009-01-01

    This slide presentation summarizes the status of the various elements of the first stage of the Ares I vehicle. It includes views of the first stage in relation to the complete Ares rocket, details of the first stage, upgrades for the Ares, the Avionics system, and the thrust oscillation system. There are also pictures from the testing.

  6. Ares I First Stage Progress

    NASA Technical Reports Server (NTRS)

    Brasfield, Fred

    2009-01-01

    Building on the legacy of the Space Shuttle and other NASA space exploration initiatives, the propulsion for the Ares I First Stage will be a Shuttle derived reusable solid rocket motor. Significant progress has been made to date by the Ares First Stage Team. This brief status provides an update on the design and development of the Ares First Stage propulsion system.

  7. Hypolipemia associated with the wasting condition of rabbits infected with Strongyloides papillosus.

    PubMed

    Nakamura, Y; Motokawa, M

    2000-02-29

    Rabbits develop a wasting condition in the intestinal stage of Strongyloides papillosus infection. Serum inflammatory cytokine and lipid profiles were investigated in five rabbits infected with S. papillosus and five uninfected pair-fed controls to ascertain whether the disease is inflammatory cytokine-mediated cachexia. Tumor necrosis factor alpha (TNF alpha) was detected in one infected animal at Day 7 after infection. Interleukin (IL)-1 was detected in three infected, and one control, animals at Day 28. IL-6 remained unchanged in both the groups. Infected animals developed hypolipemia, including hypotriglyceridemia in the intestinal stage of infection. Control animals lost body weight in the same manner as the infected animals, but had elevated cholesterols and phospholipids with normal triglyceride concentrations. The results suggested that the wasting condition has no association with cachexia induced by TNF alpha. IL-1 or IL-6, and that hepatic function for lipid synthesis is affected during the intestinal stage of S. papillosus infection. PMID:10681033

  8. Dendritic cell function and antigen presentation in malaria.

    PubMed

    Cockburn, Ian A; Zavala, Fidel

    2016-06-01

    Due to the diverse roles T cells play in protection against malaria as well as pathogenesis it is critical to know which cells present antigen and the nature of the antigens they present. During pre-erythrocytic stages of infection, cutting-edge imaging studies have shown how Plasmodium antigens are presented during both the priming and effector phases of the protective CD8+ T cell response. During blood stages, pathology is in part due to the loss of DC function and the action of pathogenic T cells in the brain. Recently endothelial cells presenting malaria antigen to cognate T cells have emerged as critical players in malaria pathogenesis. Manipulating these processes may inform both vaccine design and the development of therapies for cerebral malaria. PMID:26845735

  9. Evolution of Staged Versus Primary Closure of Gastroschisis

    PubMed Central

    Kidd, Joseph N.; Jackson, Richard J.; Smith, Samuel D.; Wagner, Charles W.

    2003-01-01

    Objective Since the introduction of a preformed silo to the authors’ practice in 1997, there has been a decrease in primary closure of gastroschisis. To clarify the impact of this change, the authors reviewed their results over the past 10 years. Methods From patient records, the authors abstracted the closure method, mechanical ventilation days, time to full feeds, mechanical and infectious complications, and length of stay. The authors compared groups using the Student t test and the Mann-Whitney test, as appropriate. Results Between 1993 and the present, 124 patients were identified. Between 1993 and 1997, 38 children presented with gastro-schisis. Thirty-two (84.2%) closures were primary and six (18.8%) were staged. After 1997, the authors treated 80 children with gastroschisis. There were 27 (33.8%) primary and 53 (66.2%) staged closures. Six patients with other lethal anomalies were excluded. Length of stay and ventilator days were higher for the staged closure group, but infection and mechanical complications were less common in the staged closure group. The time to full feeds did not differ. Conclusions A lower incidence of infection and complications related to abdominal compartment syndrome has made staged closure of gastroschisis more common in the authors’ practice. While it has resulted in a longer hospital stay, staged closure decreases the risk of long-term bowel dysfunction and need for reoperation. PMID:12796571

  10. Frog Virus 3 DNA Replication Occurs in Two Stages

    PubMed Central

    Goorha, R.

    1982-01-01

    Viral DNA synthesis in frog virus 3 (FV3)-infected cells occurs both in the nucleus and in the cytoplasm (Goorha et al., Virology 84:32-51, 1978). Relationships between viral DNA molecules synthesized in these two compartments and their role in the virus replication were examined. The data presented here suggest that (i) FV3 DNA replicated in two stages and (ii) nucleus and cytoplasm were the sites of stages 1 and 2 of DNA replication, respectively. Stages 1 and 2 were further distinguished by their temporal appearance during infection and by the sizes of the replicating DNA as determined by sedimentation in neutral sucrose gradients. In stage 1, replicating molecules, between the size of unit and twice the unit length, were produced early in infection (2 h postinfection). In contrast, stage 2 of DNA replication occurred only after 3 h postinfection, and replicating molecules were large concatemers. Results of pulse-chase experiments showed that the concatemeric DNA served as the precursor for the production of mature FV3 DNA. Denaturation of concatemeric DNA with alkali or digestion with S1 nuclease reduced it to less than genome size molecules, indicating the presence of extensive single-stranded regions. Analysis of replicating DNA by equilibrium centrifugation in CsCl gradients after a pulse-chase suggested that these single-stranded regions were subsequently repaired. Based on these and previous data, a scheme of FV3 replication is presented. According to this scheme, FV3 utilizes the nucleus for early transcription and stage 1 of DNA replication. The viral DNA is then transported to the cytoplasm, where it participates in stage 2 DNA replication to form a concatemeric replication complex. The processing of concatemers to produce mature viral DNA and virus assembly also occurs in the cytoplasm. This mode of replication is strikingly different from any other known DNA virus. PMID:7109033

  11. [Malassezia infections].

    PubMed

    Sei, Yoshihiro

    2012-01-01

    Although Malassezia yeasts are a part of the normal microflora, under certain conditions they can cause superficial skin infection Pityriasis versicolor, Malassezia folliculitis. Lipophilic yeasts are being considered as major opportunistic pathogens for a very long time. Most of the yeasts show an absolute requirement for long fatty acid chains and specific procedures are required for their isolation, conservation and identification. To date, the genus is composed of one non lipid-dependent species M. pachydermatis and lipid-dependent species M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta, M. slooffiae, M. dermatis, M. yamatoensis, M. japonica, M. nana, M. caprae, M. equina, M. cuniculi. PMID:22467125

  12. Stage Acquisition and Stage Use. An Appraisal of Stage Displacement Explanations of Variation in Moral Reasoning.

    ERIC Educational Resources Information Center

    Levine, Charles G.

    1979-01-01

    Evaluates the differing perspectives of Kohlberg and Turiel on moral reasoning. Both perspectives use stage displacement models to depict moral development and assume that as ontogenesis proceeds, the role played by earleir acquired moral stages becomes increasingly insignificant in comparison with the role played by more advanced stages. The…

  13. [Stage 1 testicular seminoma].

    PubMed

    Gross, E; Champetier, C; Pointreau, Y; Zaccariotto, A; Dubergé, T; Chauvet, B

    2010-11-01

    Testicular cancer is rare, representing only 1 % of malignant tumors, but the most common cancer in young men, 15 to 35 years. Adjuvant radiotherapy after orchidectomy in testicular seminoma stage I, reduces risk of relapse. It aims to eradicate micro-metastatic disease in lymph drainage territories. In the case of adjuvant radiotherapy, the relapse-free survival of 96 % with an overall survival of 98 % at 5 years. The irradiation volume is made up of lymph nodes paraaortic which it is possible to add the ipsilateral renal hilum to the testicular lesion. The current recommended dose is 20 Gy in 10 fractions and 2 weeks, usually delivered by two antero-posterior beams. The acute toxicities, mainly represented by nausea and diarrhea are usually quickly resolved to the end of irradiation. Regarding toxicities long-term, preservation of semen should be considered after surgery because of fear of infertility post-treatment. The risk of second cancer associated with exposure to ionizing radiation, albeit small, is especially important to consider these patients to significant life expectancy. Nevertheless, developments in radiotherapy techniques and lower doses and irradiated volumes can probably reduce this risk further. PMID:21129662

  14. 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

  15. 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

  16. Infective endocarditis.

    PubMed

    Holland, Thomas L; Baddour, Larry M; Bayer, Arnold S; Hoen, Bruno; Miro, Jose M; Fowler, Vance G

    2016-01-01

    Infective endocarditis (IE) is a rare, life-threatening disease that has long-lasting effects even among patients who survive and are cured. IE disproportionately affects those with underlying structural heart disease and is increasingly associated with health care contact, particularly in patients who have intravascular prosthetic material. In the setting of bacteraemia with a pathogenic organism, an infected vegetation may form as the end result of complex interactions between invading microorganisms and the host immune system. Once established, IE can involve almost any organ system in the body. The diagnosis of IE may be difficult to establish and a strategy that combines clinical, microbiological and echocardiography results has been codified in the modified Duke criteria. In cases of blood culture-negative IE, the diagnosis may be especially challenging, and novel microbiological and imaging techniques have been developed to establish its presence. Once diagnosed, IE is best managed by a multidisciplinary team with expertise in infectious diseases, cardiology and cardiac surgery. Antibiotic prophylaxis for the prevention of IE remains controversial. Efforts to develop a vaccine that targets common bacterial causes of IE are ongoing, but have not yet yielded a commercially available product. PMID:27582414

  17. 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

  18. Protective efficacy and safety of liver stage attenuated malaria parasites.

    PubMed

    Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich

    2016-01-01

    During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(-) or uis3(-) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(-) parasites protected better than uis3(-) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy. PMID:27241521

  19. Protective efficacy and safety of liver stage attenuated malaria parasites

    PubMed Central

    Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich

    2016-01-01

    During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(–) or uis3(–) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(–) parasites protected better than uis3(–) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy. PMID:27241521

  20. [Influenza infection and pregnancy].

    PubMed

    Anselem, Olivia; Floret, Daniel; Tsatsaris, Vassilis; Goffinet, François; Launay, Odile

    2013-11-01

    Pregnant woman have an increased risk of respiratory complications and hospitalization related to influenza. The flu, like any systemic infection, may also be responsible for uterine contractions constituting a threat of miscarriage or premature labor according to gestational age at which it occurs. There is no specific recommendation regarding the management of influenza-like illness in pregnant women, but a nasopharyngeal sample can be performed in the presence of respiratory or general symptoms occurring during an epidemic to search influenza and establish if a specific treatment with oseltamivir (Tamiflu(®)). Surveillance in hospital or intensive care unit may be necessary. Vaccination against influenza provides a satisfactory immunity in pregnant women and reduces the risk of respiratory complications. Transplacental passage of maternal antibody protects newborns who are more likely to have severe influenza infection and because the vaccine cannot be administered before the age of 6 months. The available data show good tolerance influenza vaccination performed during pregnancy. Since 2012, vaccination against seasonal influenza is recommended for pregnant women, whatever the stage of pregnancy at the time of the vaccination campaign. PMID:23683385

  1. 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

  2. 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.

  3. Spatial spread of the Hantavirus infection

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2015-03-01

    The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013), 10.1103/PhysRevE.87.042706]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly.

  4. Spatial spread of the Hantavirus infection.

    PubMed

    Reinoso, José A; de la Rubia, F Javier

    2015-03-01

    The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013)]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly. PMID:25871140

  5. 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.

  6. Immunity to systemic Salmonella infections.

    PubMed

    Mastroeni, Pietro

    2002-06-01

    Salmonella infections are a serious public health problem in developing countries and represent a constant concern for the food industry. The severity and the outcome of a systemic Salmonella infection depends on the "virulence" of the bacteria, on the infectious dose as well as on the genetic makeup and immunological status of the host. The control of bacterial growth in the reticuloendothelial system (RES) in the early phases of a Salmonella infection relies on the NADPH oxidase-dependent anti-microbial functions of resident phagocytes and is controlled by the innate resistance gene Nramp1. This early phase is followed by the suppression of Salmonella growth in the RES due to the onset of an adaptive host response. This response relies on the concerted action of a number of cytokines (TNFalpha, IFNgamma, IL12, IL18, and IL15), on the recruitment of inflammatory phagocytes in the tissues and on the activation of the recruited cells. Phagocytes control bacterial growth in this phase of the infection by producing reactive nitrogen intermediates (RNI) generated via the inducible nitric oxide synthase (iNOS). Clearance of the bacteria from the RES at a later stage of the infection requires the CD28-dependent activation of CD4+ TCR-alphabeta T-cells and is controlled by MHC class II genes. Resistance to re-infection with virulent Salmonella micro-organisms requires the presence of Th1 type immunological memory and anti-Salmonella antibodies. Thus, the development of protective immunity to Salmonella infections relies on the cross-talk between the humoral and cellular branches of the immune system. PMID:12108950

  7. Bloodstream infections after solid-organ transplantation.

    PubMed

    Kritikos, Antonios; Manuel, Oriol

    2016-04-01

    Solid-organ transplantation (SOT) has become the preferred strategy to treat a number of end-stage organ disease, because a continuous improvement in survival and quality of life. While preventive strategies has decreased the risk for classical opportunistic infections (such as viral, fungal and parasite infections), bacterial infections, and particularly bloodstream infections (BSIs) remain the most common and life-threatening complications in SOT recipients. The source of BSI after transplant depends on the type of transplantation, being urinary tract infection, pneumonia, and intraabdominal infections the most common infections occurring after kidney, lung and liver transplantation, respectively. The risk for candidemia is higher in abdominal-organ than in thoracic-organ transplantation. Currently, the increasing prevalence of multi-drug resistant (MDR) Gram-negative pathogens, such as extended-spectrum betalactamase-producing Enterobacteriaciae and carbapenem-resistant Klebsiella pneumoniae, is causing particular concerns in SOT recipients, a population which presents several risk factors for developing infections due to MDR organisms. The application of strict preventive policies to reduce the incidence of post transplant BSIs and to control the spread of MDR organisms, including the implementation of specific stewardship programs to avoid the overuse of antibiotics and antifungal drugs, are essential steps to reduce the impact of post transplant infections on allograft and patient outcomes. PMID:26766415

  8. [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. PMID:24182654

  9. 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. PMID:23556961

  10. 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.

  11. 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.

  12. 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.

  13. Chalimus stages of Caligus latigenitalis (Copepoda:Caligidae) parasitic on blackhead seabream from Japanese waters, with discussion of terminology used for developmental stages of caligids.

    PubMed

    Madinabeitia, Ione; Nagasawa, Kazuya

    2011-04-01

    The first and third chalimus stages and chalimus adult (previously known as young adult) of Caligus latigenitalis are described based on new material collected from the body surface of a heavily infected wild blackhead seabream Acanthopagrus schlegelii schlegelii from Hiroshima Bay, Japan. The second and fourth chalimus stages of the same species are redescribed. Adults of C. latigenitalis are characterized by possessing 2 stout marginally indented processes at the base of 2 terminal spines at distal exopodal segment of leg 4. The chalimi were identified to stage based on the structure of the frontal filament and the discrete ranges in body length. Sexual dimorphism is first observed at the third chalimus stage in the shape of the distal segment of the antenna. The total number of postnaupliar stages of C. latigenitalis is 6, including 4 semaphoronts, i.e., 1 copepodid stage consisting of 1 infective copepodid and the chalimus copepodid, 4 chalimus stages, and 1 adult stage with 1 chalimus adult and 1 mobile adult. New terminology for the developmental stages of caligid copepods is proposed herein by amending the definition of chalimus as the postnaupliar stages, as well as semaphoronts having a frontal filament for host attachment. PMID:21506770

  14. 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

  15. Shigella infections.

    PubMed

    Shears, P

    1996-04-01

    Shigella dysentery is a major public-health problem in many tropical areas. Despite improvements in water supplies and sanitation, it continues to be a disease of poor rural and urban communities and in populations affected by migration and crowding following disasters. Pathogenesis is due to colonic invasion, endotoxin, and, in Shigella dysenteriae 1, shiga toxin. As well as the local manifestations of dysentery, systemic complications include convulsions, haemolytic-uraemic syndrome, hyponatraemia and hypoglycaemia. The spread of shigella infection is most commonly person-person, although water and food-borne outbreaks have been reported. Since 1970, multiple antimicrobial resistance, particularly in Sh. dysenteriae 1, has complicated strategies for management. Multiply resistant strains have occurred in Latin America, Central Africa and southern and south-eastern Asia. No vaccines are currently available, and prevention and control will depend on public-health improvements and improved case management. PMID:8762400

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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;…

  2. Evaluation and management of the infected total knee arthroplasty.

    PubMed

    Springer, Bryan D; Scuderi, Giles R

    2013-01-01

    Infection after total knee arthroplasty (TKA) remains a difficult complication to treat. The risk of infection ranges from 0.5% to 2% for primary TKAs and 2% to 4% for revision TKAs. Several demographic studies indicate that more infections are occurring after these procedures, and infection is one of the most common reasons for TKA failure. Prevention remains the key to minimizing the risk of infection; however, little evidence-based literature exists to establish the optimal approach. Every patient with a painful TKA should be suspected of having an infection until proven otherwise. An algorithmic approach to these patients should include standard laboratory screening tests to rule out infection. Synovial fluid aspiration remains the best test for diagnosing infection. Synovial fluid white blood cell counts greater than 1,700 cells/µL and a differential greater than 69% polymorphonuclear cells should raise a high index of suspicion for infection. Several options are available to treat deep periprosthetic infection. The timing of the infection as it relates to surgery and the onset of symptoms are critical in determining treatment success. Prosthetic retention is indicated only in patients with an acute onset of infection, but its limited success reported in recent literature brings into question its role in infected TKAs. A two-stage exchange arthroplasty remains the gold standard for treatment of infection following TKA. PMID:23395040

  3. Analysis of the transmission of Trypanosoma cruzi infection through hosts and vectors.

    PubMed

    Fabrizio, María C; Schweigmann, Nicolás J; Bartoloni, Norberto J

    2016-08-01

    Calculating epidemiological measures of infection by Trypanosoma cruzi, the causative agent of Chagas disease, is complex, because it involves several species, different stages of infection in humans and multiple transmission routes. Using the next-generation matrix method, we analysed a model which considers the three stages of human infection, triatomines and dogs (the main domestic reservoirs of T. cruzi when triatomines are present) and the main transmission routes. We derived R 0 and type-reproduction numbers T. We deduced formulas for the number of new infections generated through each transmission route by each infected individual. We applied our findings in Argentine Gran Chaco. The expressions achieved allowed quantifying the high infectivity of dogs and emphasizing the epidemiological importance of the long and asymptomatic chronic indeterminate stage in humans in the spread of the infection. According to the model, it is expected that one infected human infects 21 triatomines, that 100 infected triatomines are necessary to infect one human and 34 to infect a dog, and that each dog infects on average one triatomine per day. Our results may allow quantifying the effect of control measures on infected humans, triatomines and dogs (or other highly infected vertebrate) or on a specific route of transmission, in other scenarios. PMID:27039662

  4. 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…

  5. 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.

  6. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    2016-01-01

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms. PMID:27535389

  7. 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…

  8. 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...

  9. Listeria Infections (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Listeria Infections KidsHealth > For Parents > Listeria Infections Print A ... to Call the Doctor en español Listeriosis About Listeria Listeria infections (known as listeriosis ) are rare. When ...

  10. Infections and Pregnancy

    MedlinePlus

    If you are pregnant, an infection can be more than just a problem for you. Some infections can be dangerous to your baby. You can help yourself avoid infections: Don't eat raw or undercooked meat Don' ...

  11. Experimental genital mycoplasmosis: time of infection influences pregnancy outcome.

    PubMed Central

    Brown, M B; Steiner, D A

    1996-01-01

    Genital infection of rats with Mycoplasma pulmonis causes adverse pregnancy outcome and can result in in utero spread of infection to the fetus. The current study was designed to determine whether the stage of pregnancy when infection occurs influences pregnancy outcome. Rats were inoculated with 3 X 10(7) CFU of M. pulmonis at 10 days prior to breeding (-10) or at gestational day (gd) 11 or 14 and were necropsied at gd 11, 14, or 18 or within 24 h of parturition (term). Control rats received sterile broth. M. pulmonis was isolated from the placenta, amniotic fluid, or fetal tissues only from rats infected prior to breeding (P < 0.001). All infected rats had significantly more loss of pups than did control rats (P < 0.006), but rats infected prior to breeding or at the beginning of the third trimester (gd 14) were much more likely to have fetal losses. Rats infected in the early second trimester after implantation (gd 11) did not experience severe losses. Litter sizes, total litter weight, and individual pup weight from all infected rats, regardless of gestational stage when infected, were significantly smaller than those of control rats (P < 0.001). On the basis of the results of this study, we conclude that the time of infection plays a major role in determination of pregnancy outcome and spread of infection from the genital tract to the respiratory tract. PMID:8675343

  12. TREATMENT OF INFECTION AFTER TOTAL KNEE ARTHROPLASTY

    PubMed Central

    Cury, Ricardo de Paula Leite; Cinagawa, Eduardo Hitoshi Tsuge; Camargo, Osmar Pedro Arbix; Honda, Emerson Kiyoshi; Klautau, Giselle Burlamaqui; Salles, Mauro José Costa

    2015-01-01

    ABSTRACT Objectives: To identify and compare the rate of success of therapeutic modalities applied in surgeries for the treatment of infections associated with total knee arthroplasty (TKA), and to evaluate the functional outcome and pain in different therapeutic modalities by means of quality of life scores. Methods: We evaluated all patients who developed periprosthetic infection after TKA for primary or secondary osteoarthritis, in the period from January 1st, 2008 to December 31st, 2010. Results: In the study period, 29 patients with TKA had infection, and 12 of these underwent debridement and retention of the prosthesis (D+R), seven received two-stage and six one-stage exchange arthroplasties, and four patients were treated with suppressive antibiotic therapy because they could not undergo another surgical procedure. Conclusion: The D+R, one-stage revision and two-stage revision success rates were 75%, 83.3%, and 100%, respectively. The best results of quality of life (QoL) and function occur in patients undergoing D+R. In contrast, the worst QoL and functional results were obtained in patients treated with two-stage revision arthroplasty. Level of Evidence II, Prognostic Studies - Investigating the Effect of a Patient Characteristic on the Outcome of Disease. PMID:26981029

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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). ...

  19. CROI 2016: Neurologic Complications of HIV Infection.

    PubMed

    Spudich, Serena S; Ances, Beau M

    2016-01-01

    The brain remains a major target for HIV infection and a site of potential complications for HIV-infected individuals. Emerging data presented at the 2016 Conference on Retroviruses and Opportunistic Infections suggest that during the early stages of infection, activated CD4+ cells may traffic the virus into the central nervous system (CNS). HIV is detectable in cells and tissues of the CNS in some individuals despite suppressive antiretroviral treatment. A potential source of cerebrospinal fluid HIV escape may be compartmentalized HIV replication within macrophage lineage cells. Virally infected cells can traffic out of the CNS and may have the potential to reseed the systemic compartment. Additional modifiers of HIV-associated neurocognitive disorder (HAND) were identified, including female sex and hepatic dysfunction. Large epidemiologic studies reported an elevated risk of stroke among HIV-infected individuals, related to traditional vascular risk factors, history of recreational drug use, and HIV measures (lower CD4+ cell nadir and higher viral load). Brain imaging may provide a noninvasive means for detecting early changes in the brain associated with HIV infection and may assist in prognosis of HAND. Some potential adjunctive therapies to standard antiretroviral therapy for HIV-infected individuals were considered. PMID:27398860

  20. Distribution of potato spindle tuber viroid in reproductive organs of petunia during its developmental stages.

    PubMed

    Matsushita, Yosuke; Tsuda, Shinya

    2014-09-01

    Embryo infection is important for efficient seed transmission of viroids. To identify the major pattern of seed transmission of viroids, we used in situ hybridization to histochemically analyze the distribution of Potato spindle tuber viroid (PSTVd) in each developmental stage of petunia (flowering to mature seed stages). In floral organs, PSTVd was present in the reproductive tissues of infected female × infected male and infected female × healthy male but not of healthy female × infected male before embryogenesis. After pollination, PSTVd was detected in the developed embryo and endosperm in all three crosses. These findings indicate that PSTVd is indirectly delivered to the embryo through ovule or pollen during the development of reproductive tissues before embryogenesis but not directly through maternal tissues as cell-to-cell movement during embryogenesis. PMID:25116641