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  1. Significant Depletion of CD4+ T Cells Occurs in the Oral Mucosa during Simian Immunodeficiency Virus Infection with the Infected CD4+ T Cell Reservoir Continuing to Persist in the Oral Mucosa during Antiretroviral Therapy

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    Jeffy George

    2015-01-01

    Full Text Available Human and simian immunodeficiency virus (HIV and SIV infections are characterized by manifestation of numerous opportunistic infections and inflammatory conditions in the oral mucosa. The loss of CD4+ T cells that play a critical role in maintaining mucosal immunity likely contributes to this process. Here we show that CD4+ T cells constitute a minor population of T cells in the oral mucosa and display a predominantly central memory phenotype mirroring other mucosal sites such as the rectal mucosa. Chronic SIV infection was associated with a near total depletion of CD4+ T cells in the oral mucosa that appear to repopulate during antiretroviral therapy (ART. Repopulating CD4+ T cells harbored a large fraction of Th17 cells suggesting that ART potentially reconstitutes oral mucosal immunity. However, a minor fraction of repopulating CD4+ T cells harbored SIV DNA suggesting that the viral reservoir continues to persist in the oral mucosa during ART. Therapeutic approaches aimed at obtaining sustainable CD4+ T cell repopulation in combination with strategies that can eradicate the latent viral reservoir in the oral mucosa are essential for better oral health and long-term outcome in HIV infected patients.

  2. Laboratory diagnosis of persistent human chlamydial infection

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    Mirja ePuolakkainen

    2013-12-01

    Full Text Available Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.

  3. Persistent viral infections and immune aging.

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    Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2011-07-01

    Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Persistent Psychosis Occurring in a Patient Receiving Cycloserine ...

    African Journals Online (AJOL)

    A case of cycloserineinduced psychosis persisting after discontinuation of the drug in the treatment of multidrug resistant tuberculosis in a 26 year old male who was been managed in the hospital for multidrug resistant tuberculosis on daily doses of Cycloserine 500mg, Pyrazinamide 1.2g, Proteonamide 500mg, Kanamy c ...

  5. Superinfection occurs in Anaplasma phagocytophilum infected sheep irrespective of infection phase and protection status

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    Bergström Karin

    2009-10-01

    Full Text Available Abstract Background Anaplasma phagocytophilum infection in domestic ruminants is widespread in the coastal areas of southern Norway. The bacteria may persist in mammalian hosts. Several genetic variants of A. phagocytophilum exist. In the present study, we investigate whether superinfection occurs in the acute and persistent phase of the infection. Methods Five-month-old lambs of the Norwegian Dala breed were experimentally infected with two 16S rRNA gene variants of A. phagocytophilum, i.e. A. phagocytophilum variant 1 (GenBank accession number M73220 and variant 2 (GenBank acc. no. AF336220. Eighteen lambs were used, two lambs in each group. Eight groups were experimentally inoculated with either variant 1 or 2 on day 0. Six of these groups were then challenged with the other variant on either days 7, 42 or 84, respectively. One group was left uninfected. The occurrence of A. phagocytophilum in blood samples was determined using semi-nested PCR analysis and gene sequencing. Specific antibodies were measured by an indirect immunofluorescence antibody assay (IFA. Results A. phagocytophilum variant 1 and 2 differed significantly with regards to clinical reaction and cross-immunity in infected lambs. Both variants were found in the blood after challenge. However, variant 1 was detected most frequently. Conclusion The present experiment indicates that superinfection of different genotypes occurs during the acute as well as the persistent phase of an A. phagocytophilum infection, even in lambs protected against the challenged infection.

  6. Pathogenic characteristics of persistent feline enteric coronavirus infection in cats

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    Vogel, Liesbeth; Van der Lubben, Mariken; Te Lintelo, Eddie G.; Bekker, Cornelis P.J.; Geerts, Tamara; Schuijff, Leontine S.; Grinwis, Guy C.M.; Egberink, Herman F.; Rottier, Peter J.M.

    2010-01-01

    Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed. PMID:20663472

  7. Persistent hepatitis virus infection and immune homeostasis

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    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  8. Necrotizing Soft Tissue Infection Occurring after Exposure to Mycobacterium marinum

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    Shivani S. Patel

    2014-01-01

    Full Text Available Cutaneous infections caused by Mycobacterium marinum have been attributed to aquarium or fish exposure after a break in the skin barrier. In most instances, the upper limbs and fingers account for a majority of the infection sites. While previous cases of necrotizing soft tissue infections related to M. marinum have been documented, the importance of our presenting case is to illustrate the aggressive nature of M. marinum resulting in a persistent necrotizing soft tissue infection of a finger that required multiple aggressive wound debridements, followed by an amputation of the affected extremity, in order to hasten recovery.

  9. Intrauterine Transmission of Anaplasma phagocytophilum in Persistently Infected Lambs

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    Snorre Stuen

    2018-02-01

    Full Text Available Anaplasma phagocytophilum, which causes the disease tick-borne fever (TBF, is the most important tick-borne pathogen in European animals. TBF may contribute to severe welfare challenges and economic losses in the Norwegian sheep industry. The bacterium causes a persistent infection in sheep and several other animal species. The objective of this study was to investigate whether intrauterine transmission occurs in persistently infected sheep. The study included thirteen 5–6-month-old unmated ewes, of which twelve were experimentally infected with A. phagocytophilum (GenBank acc. no. M73220. Four to six weeks later, all ewes were mated, and nine became pregnant. Blood samples were collected from these ewes and their offspring. If the lamb died, tissue samples were collected. The samples were analyzed with real-time PCR (qPCR targeting the msp2 gene. PCR-positive samples were further analyzed by semi-nested PCR and 16S rDNA sequencing. A total of 20 lambs were born, of which six died within two days. Six newborn lambs (30% were PCR-positive (qPCR, of which one was verified by 16S rDNA sequencing. The present study indicates that intrauterine transmission of A. phagocytophilum in persistently infected sheep may occur. The importance of these findings for the epidemiology of A. phagocytophilum needs to be further investigated.

  10. Persistent infection with ebola virus under conditions of partial immunity.

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    Gupta, Manisha; Mahanty, Siddhartha; Greer, Patricia; Towner, Jonathan S; Shieh, Wun-Ju; Zaki, Sherif R; Ahmed, Rafi; Rollin, Pierre E

    2004-01-01

    Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for >/==" BORDER="0">25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting

  11. Persistent infection caused by Hobi-like pestivirus.

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    Decaro, Nicola; Losurdo, Michele; Lucente, Maria Stella; Sciarretta, Rossana; Mari, Viviana; Larocca, Vittorio; Elia, Gabriella; Cavaliere, Nicola; Martella, Vito; Fasanella, Antonio; Buonavoglia, Canio

    2013-04-01

    A calf persistently infected by Hobi-like pestivirus was monitored for about 6 months, displaying clinical signs typical of bovine viral diarrhea virus persistent infection and shedding the virus through all body secretions, with maximal titers detected in urine. This report provides new insights into the pathogenesis of the emerging pestivirus.

  12. Effects of interferon on cultured cells persistently infected with viruses

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    Crespi, M

    1986-01-01

    The role of interferon (IFN) in viral persistence at the cellular level was investigated. Two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, C11 cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. The aim of this work was to determine what effect IFN had in these infections in terms of its antiviral and antiproliferative effects; which of the two major IFN-induced pathways, E enzyme or protein kinase were induced; whether there were any differences in sensitivity to IFN between the DNA and RNA virus persistent infections. The anti-viral effect of IFN was examined by its ability to inhibit Sindbis virus replication using a radioimmunoassay system. The antiproliferative effect of IFN was determined by cell counting and /sup 3/H-thymidine incorporation. The activation of the ribonuclease F, determined by the inhibition of /sup 3/H-leucine incorporation after introduction of 2-5 actin into the cells, was variable, being activated in all cell lines with the exception of the PLC/PRF/5, Hep 3B and Hep G2 cells. Major differences between the two DNA persistent infections and the two RNA persistent infections were found. No correlation was found between the presence of HBV or SV40 persistent infections and the sensitivity of the cell lines to IFN. Both the SSPE and Sendai virus persistent infections were resistant to the antiviral and antiproliferative effect of IFN.

  13. Biosynthesis of measles virus hemagglutinin in persistently infected cells

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    Bellini, W.J.; Silver, G.D.; McFarlin, D.E.

    1983-01-01

    The synthesis of the hemagglutinin (HA) glycoprotein of measles virus was investigated in a persistently infected cell line using a monoclonal anti-HA. The synthesis of the HA protein was shown to be associated with the rough endoplasmic reticulum. The unglycosylated (HA 0 ) apoprotein is synthesized as a 65.000 dalton peptide and is inserted into the rough endoplasmic reticulum as a transmembrane protein with approximately 2 to 3000 daltons of the peptide exposed to the cytoplasmic membrane surface. Primary glycosylation of the HA protein was found to occur through the lipid-linked carrier, dolichol-phosphate, as determined by inhibition of glycosylation by tunicamycin. Glycosylation, however, was not a prerequisite for membrane insertion. Endo-β-N-acetyl-Glucosaminidase H digestion of the fully glycosylated HA protein indicated that both simple and complex oligosaccharides are present on the surface glycoprotein. (Author)

  14. Persistent and late occurring lesions in irradiated feet of rats: their clinical relevance

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    Hopewell, J.W.

    1982-01-01

    Radiation-induced deformity, as characterized by tissue loss, has been investigated in rat feet. The acute epithelial response and the loss of deeper tissues occur concomitantly after irradiation. The greatest loss of tissue (severe deformity) was produced in feet where the healing of the epithelial reaction was greatly delayed. While deformity will clearly continue to ''persist'' after the acute reaction has healed it is misleading to refer to this lesion as ''late'' damage. A late-occurring lesion, not previously described in the literature, can be produced in the rat foot by high doses of radiation delivered in such a way that moist desquamation is avoided, i.e. by extending the total treatment time. Parallels are drawn between reactions in rodents and those in the skin of pig and man. (author)

  15. Environmental Persistence Influences Infection Dynamics for a Butterfly Pathogen.

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    Dara A Satterfield

    Full Text Available Many pathogens, including those infecting insects, are transmitted via dormant stages shed into the environment, where they must persist until encountering a susceptible host. Understanding how abiotic conditions influence environmental persistence and how these factors influence pathogen spread are crucial for predicting patterns of infection risk. Here, we explored the consequences of environmental transmission for infection dynamics of a debilitating protozoan parasite (Ophryocystis elektroscirrha that infects monarch butterflies (Danaus plexippus. We first conducted an experiment to observe the persistence of protozoan spores exposed to natural conditions. Experimental results showed that, contrary to our expectations, pathogen doses maintained high infectivity even after 16 days in the environment, although pathogens did yield infections with lower parasite loads after environmental exposure. Because pathogen longevity exceeded the time span of our experiment, we developed a mechanistic model to better explore environmental persistence for this host-pathogen system. Model analysis showed that, in general, longer spore persistence led to higher infection prevalence and slightly smaller monarch population sizes. The model indicated that typical parasite doses shed onto milkweed plants must remain viable for a minimum of 3 weeks for prevalence to increase during the summer-breeding season, and for 11 weeks or longer to match levels of infection commonly reported from the wild, assuming moderate values for parasite shedding rate. Our findings showed that transmission stages of this butterfly pathogen are long-lived and indicated that this is a necessary condition for the protozoan to persist in local monarch populations. This study provides a modeling framework for future work examining the dynamics of an ecologically important pathogen in an iconic insect.

  16. Occurance and distribution of poty viruses infecting garlic in Pakistan

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    Gilani, S.T.; Hameed, S.; Shah, H.

    2016-01-01

    The study was designed to detect and determine the prevalence, incidence and distribution of the poty viruses causing diseases in garlic (Allium sativum) from major garlic growing areas of Pakistan. The yellow stripes, mosaic and chlorotic spot symptoms of the disease resemble the viral infection in garlic reported to occur worldwide. Altogether 690 samples were collected from 29 locations of Punjab and 40 locations of Khyber Pukhtunkhwa to determine the prevalence of Onion Yellow Dwarf Virus (OYDV) and Leek Yellow Stripe Virus (LYSV). Serological testing DAS-ELISA technique was used to test the samples collected from the farmer fields. Based on the DAS-ELISA poty viruses OYDV and LYSV were detected from both provinces although the percentage incidence varied from location to location. Few areas of district Punjab were found free of LYSV but OYDV was prevalent in all locations irrespective of the varieties cultivated. Maximum disease incidence was detected in Swabi (KPK) where OYDV was 90percent and LYSV was 38 percent while in Punjab major disease incidence of OYDV (87.14 percent) and LYSV (91.44 percent) was found in Sialkot. (author)

  17. Toxoplasma depends on lysosomal consumption of autophagosomes for persistent infection.

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    Di Cristina, Manlio; Dou, Zhicheng; Lunghi, Matteo; Kannan, Geetha; Huynh, My-Hang; McGovern, Olivia L; Schultz, Tracey L; Schultz, Aric J; Miller, Alyssa J; Hayes, Beth M; van der Linden, Wouter; Emiliani, Carla; Bogyo, Matthew; Besteiro, Sébastien; Coppens, Isabelle; Carruthers, Vern B

    2017-06-19

    Globally, nearly 2 billion people are infected with the intracellular protozoan Toxoplasma gondii 1 . This persistent infection can cause severe disease in immunocompromised people and is epidemiologically linked to major mental illnesses 2 and cognitive impairment 3 . There are currently no options for curing this infection. The lack of effective therapeutics is due partly to a poor understanding of the essential pathways that maintain long-term infection. Although it is known that Toxoplasma replicates slowly within intracellular cysts demarcated with a cyst wall, precisely how it sustains itself and remodels organelles in this niche is unknown. Here, we identify a key role for proteolysis within the parasite lysosomal organelle (the vacuolar compartment or VAC) in turnover of autophagosomes and persistence during neural infection. We found that disrupting a VAC-localized cysteine protease compromised VAC digestive function and markedly reduced chronic infection. Death of parasites lacking the VAC protease was preceded by accumulation of undigested autophagosomes in the parasite cytoplasm. These findings suggest an unanticipated function for parasite lysosomal degradation in chronic infection, and identify an intrinsic role for autophagy in the T. gondii parasite and its close relatives. This work also identifies a key element of Toxoplasma persistence and suggests that VAC proteolysis is a prospective target for pharmacological development.

  18. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  19. Chronic hepatitis caused by persistent parvovirus B19 infection

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    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

  20. Polypeptide synthesis in alphavirus-infected aedes albopictus cells during the establishment of persistent infection

    International Nuclear Information System (INIS)

    Richardson, M.A.; Boulton, R.W.; Raghow, R.S.; Dalgarno, L.

    1980-01-01

    Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cells, RRV reached peak titres at 34-48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and <5 per cent of cells assayed as infected. There was not shutdown of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s).The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persistently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK cells host protein synthesis was severely inhibited and by 9-11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity. (author)

  1. Pathological and Molecular Based Study of Naturally Occurring Lentivirus Infection

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    Fazal Mahmood*, Ahrar Khan, Muhammad Zargham Khan, Riaz Hussain1, Shafia Tehseen Gul and Abu Baker Siddique2

    2012-10-01

    Full Text Available The present study describes the multicentric lymphosarcoma associated with lymphoid interstitial pneumonia in indigenous breeds of sheep and goats in Pakistan. Serum samples from sheep (n=93 and goats (n=129 were screened for ovine lentivirus using agar gel immunodiffusion test. Overall, 7.52 and 3.87% seroprevalence was recorded in sheep and goat, respectively. During necropsy of sheep (n=3 and goats (n=4, gross lesions including dark color liver with multifocal whitish areas, unilaterally lungs consolidation with granular appearance of cut surface were observed. Mediastinal lymph nodes were swollen and arranged in chain like fashion. Histopathologically, liver parenchyma exhibited extensive proliferation of neoplastic cells of lymphocytic series. Metastatic cells in the form of follicular pattern in the lungs, spleen and mediastinal lymph nodes were also observed. Brain tissue exhibited degenerative changes in the neuron and perivascular cuffing. The PCR product size approximately 300 bp from lung tissue confirmed viral infection.

  2. Naturally Occurring Egg Drop Syndrome Infection in Turkeys

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    Z. Biđin

    2007-01-01

    Full Text Available A decrease in the egg quality, production, fertility and hatchability without serious clinical signs of illness was recorded in turkey fl ocks in Croatia at the beginning of 2002. It was assumed that the egg drop syndrome virus might be one of the etiological agents responsible for the abnormalities in the egg production. The systematic serological monitoring, using a haemagglutination inhibition test, showed that the antibodies to the egg drop syndrome virus existed in 94.4 and 55.1% of the sera analysed in 2002 and 2003, respectively. The haemagglutination inhibition titres ranged from 16 to 128. The sera samples were randomly collected from 11 - to 46-week-old hens from the affected fl ocks. The serological evidence of the egg drop syndrome virus infection was confirmed by detection of the presence of the virus genome in the turkey sera by the polymerase chain reaction. Vaccination of the 18- and 25-week-old turkey hens against the egg drop syndrome virus started in March 2003. After this period, the presence of antibodies to the egg drop syndrome virus (the haemagglutination inhibition titres between 16 and 256 was found in 96.7% of the analysed sera, while the egg production reached normal or higher values for the Nicholas hybrid line of turkeys.

  3. Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates

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    Tramper-Stranders, G. A.; van der Ent, C. K.; Molin, Søren

    2012-01-01

    Clin Microbiol Infect 2012; 18: 567574 Abstract Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates...

  4. Persistent BVDV infection in mousedeer infects calves - Do we know the reservoirs for BVDV?

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    Uttenthal, Åse; Grøndahl, M.J.; Houe, Hans

    2005-01-01

    Bovine virus diarrhoea virus (BVDV)-1f was isolated from a Lesser Malayan Mousedeer in Copenhagen Zoo during a routine screening. Analysis of animals related to the Copenhagen mousedeer revealed that its mother and all siblings were virus positive, a pattern also seen for persistently infected (P...

  5. Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

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    Sara Muñoz-González

    Full Text Available It is well established that trans-placental transmission of classical swine fever virus (CSFV during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs

  6. Antimicrobial defence and persistent infection in insects revisited.

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    Makarova, Olga; Rodríguez-Rojas, Alexandro; Eravci, Murat; Weise, Chris; Dobson, Adam; Johnston, Paul; Rolff, Jens

    2016-05-26

    Insects show long-lasting antimicrobial immune responses that follow the initial fast-acting cellular processes. These immune responses are discussed to provide a form of phrophylaxis and/or to serve as a safety measure against persisting infections. The duration and components of such long-lasting responses have rarely been studied in detail, a necessary prerequisite to understand their adaptive value. Here, we present a 21 day proteomic time course of the mealworm beetle Tenebrio molitor immune-challenged with heat-killed Staphylococcus aureus The most upregulated peptides are antimicrobial peptides (AMPs), many of which are still highly abundant 21 days after infection. The identified AMPs included toll and imd-mediated AMPs, a significant number of which have no known function against S. aureus or other Gram-positive bacteria. The proteome reflects the selective arena for bacterial infections. The results also corroborate the notion of synergistic interactions in vivo that are difficult to model in vitroThis article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. © 2016 The Author(s).

  7. Using Natural Products to Treat Resistant and Persistent Bacterial Infections

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    Deering, Robert W.

    -lactams, tetracyclines, aminoglycosides, and chloramphenicol. The efflux pump inhibitory mechanism was further proved through an accumulation assay with the Hoechst dye 33342. In chapter three, we report the discovery of a 1,2-benzisoxazole with new antibacterial activity against MDR A. baumannii, a pathogen with a critical need of new treatments. This compound was produced by bacterial fermentation and synthetic preparation and shows minimum inhibitory concentrations as low as 6.25 ?g/mL against a panel of four clinically relevant A. baumannii strains. Key structure activity relationships were demonstrated using synthetic analogs of the lead 1,2-benzisoxazole. We advocate for further studies to advance the development of this compound. The third study, describes an in vitro quiescent state of uropathogenic E. coli (UPEC) and bacteria-produced signals that can prevent this state. Quiescence was seen in the classic UPEC strain CFT073 only when grown on glucose M9 minimal medium agar plates seeded with ≤10 6 CFU. Interestingly, this quiescent state is seen in 80% of E. coli phylogenetic group B2 multilocus sequence type 73 strains, as well as 22.5% of randomly selected UPEC strains isolated from community acquired urinary tract infections in Denmark. Furthermore, it was determined that CFT073 forms a high persister cell fraction under these growth conditions. Both the persistent and quiescent states were inhibited significantly by a cocktail of lysine, tyrosine, and methionine at concentrations relevant to those in human urine. The use of CFT073 mini-Tn5 metabolic mutants ( gnd, gdhA, pykF, sdhA, and zwf) showed that both quiescence and persistence require a complete TCA cycle, but that the dormant states differ in that persistence requires a non-functional rpoS gene and quiescence does not. These results suggest that interference with these central metabolic pathways may be able to mitigate UPEC infections. In the fifth chapter, cranberry oligosaccharides and related compounds were

  8. Combined Therapy at Persistent Herpes Virus Infection in Sickly Children

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    F. S. Kharlamova

    2012-01-01

    Full Text Available We examined 40 sickly children with recurrent croup (RC — 28 and bronchial obstruction (ROB — 8, (RC + ROB — 4 aged from 18 months till 14 years. We found that high frequency of persistent herpes viruses usually occurs as associations with CMV, EBV and human herpes virus 6 type. We substantiated anti viral and immune corrective therapy in two schemes compared in efficacy: the 1st group was administered monotherapy with Viferon, and the 2nd group received combined therapy Viferon + Arbidol in doses according to the age during three months. We received a more expressed clinical immunologic effect from the therapy with decreased antigenic load and frequency of recurrence of RC and ROB with Viferon application in suppositories in combination with Arbidol per orally in the intermittent scheme during three months. 

  9. Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

    International Nuclear Information System (INIS)

    Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2005-01-01

    In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies

  10. A new model of Hantaan virus persistence in mice: the balance between HTNV infection and CD8+ T-cell responses

    International Nuclear Information System (INIS)

    Araki, Koichi; Yoshimatsu, Kumiko; Lee, Byoung-Hee; Kariwa, Hiroaki; Takashima, Ikuo; Arikawa, Jiro

    2004-01-01

    We established a viral persistence model that involves the adoptive transfer of spleen cells from immunocompetent mice (H-2 d ) into Hantaan virus (HTNV)-infected severe combined immunodeficient (SCID, H-2 d ) mice. The infection is maintained despite the presence of neutralizing antibodies, without apparent signs of disease, and there is a correlation between HTNV persistence and the lack of HTNV-specific CD8 + T cells. In addition, disseminated HTNV infection before the initiation of immune responses appears to be important for virus persistence. The suppression of HTNV-specific CD8 + T cells in the present model appears to occur at the periphery. The present study also demonstrates that CD8 + T cells contribute to the clearance of HTNV. Thus, it seems that HTNV-specific CD8 + T cells play a key role in HTNV persistence in mice. This model of viral persistence is useful for studies of immune responses and immunocytotherapy against viral infection

  11. Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

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    Otani, Sanae [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ayata, Minoru, E-mail: maverick@med.osaka-cu.ac.jp [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Takeuchi, Kaoru [Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki (Japan); Takeda, Makoto [Department of Virology 3, National Institute of Infectious Diseases, Tokyo (Japan); Shintaku, Haruo [Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ogura, Hisashi [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan)

    2014-08-15

    Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

  12. Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

    International Nuclear Information System (INIS)

    Otani, Sanae; Ayata, Minoru; Takeuchi, Kaoru; Takeda, Makoto; Shintaku, Haruo; Ogura, Hisashi

    2014-01-01

    Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene

  13. Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen.

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    Cathy Steel

    2011-04-01

    Full Text Available Chronic lymphatic filarial (LF infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN, microfilaria (mf positive infected patients (Inf had a reduced CD4 central memory (T(CM compartment. In addition, Inf patients tended to have more effector memory cells (T(EM and fewer effector cells (T(EFF than did ENs giving significantly smaller T(EFF:T(EM ratios. These contracted T(CM and T(EFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf. Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells, was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children

  14. Persistent Low-Risk and High-Risk Human Papillomavirus Infections of the Uterine Cervix in HIV-Negative and HIV-Positive Women

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    Sally N. Adebamowo

    2017-07-01

    Full Text Available BackgroundThe prevalence, persistence, and multiplicity of human papillomavirus (HPV infection appears different comparing HIV-positive to HIV-negative women. In this study, we examined prevalent, persistent, and multiple low- and high-risk cervical HPV infections in HIV-negative and HIV-positive women.MethodsWe studied 1,020 women involved in a study of HPV infection using SPF25/LiPA10. Two study visits were scheduled, at enrollment and 6 months afterward. At each study visit, research nurses used a cervical brush to collect samples of exfoliated cervical cells from the cervical os, from all the study participants. Exact logistic regression models were used to estimate associations between HIV and HPV infections.ResultsThe mean (SD age of the study participants was 38 (8 years, 56% were HIV-negative and 44% were HIV-positive. Among HIV-negative women at baseline, single low-risk HPV (lrHPV infections occurred in 12%; multiple lrHPV in 2%; single high-risk human papillomavirus (hrHPV infections in 9%, and multiple hrHPV infections in 2%. Single lrHPV infections were persistent in 6%, but there was no persistent multiple lrHPV infections. Single hrHPV infections were persistent in 4% while multiple hrHPV infections were persistent in 0.3%. Among HIV-positive women at baseline, single lrHPV infections occurred in 19%, multiple lrHPV in 6%, single hrHPV infections in 17%, and multiple hrHPV infections occurred in 12%. Single lrHPV infections were persistent in 9%, multiple lrHPV infections in 0.6%, single hrHPV infections in 13%, while multiple hrHPV were persistent in 3%. Prevalent, persistent, and multiple infections were more common in HIV-positive women, compared to HIV-negative women. In multivariate models adjusted for age, marital status, socioeconomic status, age at sexual initiation, and douching, the odds ratios comparing HIV-positive to HIV-negative women, were 2.09 (95% CI 1.47–2.97, p < 0.001 for prevalent lrHPV, 1.26 (95% CI

  15. Mucormycosis: New Developments into a Persistently Devastating Infection.

    Science.gov (United States)

    Danion, François; Aguilar, Claire; Catherinot, Emilie; Alanio, Alexandre; DeWolf, Susan; Lortholary, Olivier; Lanternier, Fanny

    2015-10-01

    Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001

  16. Foxp3+ regulatory T cells control persistence of viral CNS infection.

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    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  17. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status.

    Science.gov (United States)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  18. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract

    Science.gov (United States)

    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...

  19. Nora virus persistent infections are not affected by the RNAi machinery.

    Science.gov (United States)

    Habayeb, Mazen S; Ekström, Jens-Ola; Hultmark, Dan

    2009-05-29

    Drosophila melanogaster is widely used to decipher the innate immune system in response to various pathogens. The innate immune response towards persistent virus infections is among the least studied in this model system. We recently discovered a picorna-like virus, the Nora virus which gives rise to persistent and essentially symptom-free infections in Drosophila melanogaster. Here, we have used this virus to study the interaction with its host and with some of the known Drosophila antiviral immune pathways. First, we find a striking variability in the course of the infection, even between flies of the same inbred stock. Some flies are able to clear the Nora virus but not others. This phenomenon seems to be threshold-dependent; flies with a high-titer infection establish stable persistent infections, whereas flies with a lower level of infection are able to clear the virus. Surprisingly, we find that both the clearance of low-level Nora virus infections and the stability of persistent infections are unaffected by mutations in the RNAi pathways. Nora virus infections are also unaffected by mutations in the Toll and Jak-Stat pathways. In these respects, the Nora virus differs from other studied Drosophila RNA viruses.

  20. Persistence, impacts and environmental drivers of covert infections in invertebrate hosts

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    Inês Fontes

    2017-11-01

    Full Text Available Abstract Background Persistent covert infections of the myxozoan, Tetracapsuloides bryosalmonae, in primary invertebrate hosts (the freshwater bryozoan, Fredericella sultana have been proposed to represent a reservoir for proliferative kidney disease in secondary fish hosts. However, we have limited understanding of how covert infections persist and vary in bryozoan populations over time and space and how they may impact these populations. In addition, previous studies have likely underestimated covert infection prevalence. To improve our understanding of the dynamics, impacts and implications of covert infections we employed a highly sensitive polymerase chain reaction (PCR assay and undertook the first investigation of covert infections in the field over an annual period by sampling bryozoans every 45 days from three populations within each of three rivers. Results Covert infections persisted throughout the year and prevalence varied within and between rivers, but were often > 50%. Variation in temperature and water chemistry were linked with changes in prevalence in a manner consistent with the maintenance of covert infections during periods of low productivity and thus poor growth conditions for both bryozoans and T. bryosalmonae. The presence and increased severity of covert infections reduced host growth but only when bryozoans were also investing in the production of overwintering propagules (statoblasts. However, because statoblast production is transitory, this effect is unlikely to greatly impact the capacity of bryozoan populations to act as persistent sources of infections and hence potential disease outbreaks in farmed and wild fish populations. Conclusions We demonstrate that covert infections are widespread and persist over space and time in bryozoan populations. To our knowledge, this is the first long-term study of covert infections in a field setting. Review of the results of this and previous studies enables us to identify

  1. Persistent spiking fever in a child with acute myeloid leukemia and disseminated infection with enterovirus

    NARCIS (Netherlands)

    Murk, J. L.; de Vries, A. C.; GeurtsvanKessel, C. H.; Aron, G.; Osterhaus, A. D.; Wolthers, K. C.; Fraaij, P. L.

    2014-01-01

    We here report a 7 year old acute myeloid leukemia patient with persistent spiking fever likely caused by chronic echovirus 20 infection. After immunoglobulin substitution fevers subsided and the virus was cleared. Enterovirus infection should be considered in immunocompromised patients with

  2. Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever?

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    James Owen Robinson

    Full Text Available BACKGROUND: Management of febrile neutropenic episodes (FE is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT in FE for initial diagnosis of infection and reassessment in persistent fever. METHODS: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples: 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS, 68 clinically documented infections (CDI, 35%; 39 deep-seated, and 61 fever of unexplained origin (FUO, 31.5%. RESULTS: At fever onset median PCT was 190 pg/mL (range 30-26'800, without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350 vs. FUO (205, 33-771; p500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771. A PCT peak >500 pg/mL (1196, 524-11950 occurred beyond 3 days of persistent fever in 17/21 (81% invasive fungal diseases (IFD. This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23 vs. 10 (3-22; p = 0.026, respectively. CONCLUSION: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses.

  3. Distribution of bovine viral diarrhoea virus antigen in persistently infected white-tailed deer (Odocoileus virginianus).

    Science.gov (United States)

    Passler, T; Walz, H L; Ditchkoff, S S; van Santen, E; Brock, K V; Walz, P H

    2012-11-01

    Infection with bovine viral diarrhoea virus (BVDV), analogous to that occurring in cattle, is reported rarely in white-tailed deer (Odocoileus virginianus). This study evaluated the distribution of BVDV antigen in persistently infected (PI) white-tailed deer and compared the findings with those from PI cattle. Six PI fawns (four live-born and two stillborn) from does exposed experimentally to either BVDV-1 or BVDV-2 were evaluated. Distribution and intensity of antigen expression in tissues was evaluated by immunohistochemistry. Data were analyzed in binary fashion with a proportional odds model. Viral antigen was distributed widely and was present in all 11 organ systems. Hepatobiliary, integumentary and reproductive systems were respectively 11.8, 15.4 and 21.6 times more likely to have higher antigen scores than the musculoskeletal system. Pronounced labelling occurred in epithelial tissues, which were 1.9-3.0 times likelier than other tissues to contain BVDV antigen. Antigen was present in >90% of samples of liver and skin, suggesting that skin biopsy samples are appropriate for BVDV diagnosis. Moderate to severe lymphoid depletion was detected and may hamper reliable detection of BVDV in lymphoid organs. Muscle tissue contained little antigen, except for in the cardiovascular system. Antigen was present infrequently in connective tissues. In nervous tissues, antigen expression frequency was 0.3-0.67. In the central nervous system (CNS), antigen was present in neurons and non-neuronal cells, including microglia, emphasizing that the CNS is a primary target for fetal BVDV infection. BVDV antigen distribution in PI white-tailed deer is similar to that in PI cattle. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Pyrosequencing Analysis of Cryogenically Ground Samples from Primary and Secondary/Persistent Endodontic Infections.

    Science.gov (United States)

    Keskin, Cangül; Demiryürek, Ebru Özsezer; Onuk, Ertan Emek

    2017-08-01

    This study aimed to characterize the microbial communities of primary and secondary/persistent endodontic infections using high-throughput pyrosequencing from the pulverized samples. The roots of 20 extracted human teeth with primary endodontic infection and 20 teeth with secondary/persistent endodontic infection were collected. The outer surfaces of the roots were disinfected, and whole roots were cryopulverized. 16S amplicon pyrosequencing data from the DNA extracted from the pulverized root powders were obtained, and microorganism abundance and diversity were calculated. Data were analyzed using statistical and bioinformatic methods. Pyrosequencing analysis resulted a total of 2,606,128 sequences from 40 samples. A total of 15 phyla, 160 genera, and 368 species were detected. No significant difference between primary and secondary/persistent endodontic infections was found regarding the diversity and richness of operational taxonomic units at the phyla, genera, and species levels (P > .005). The present study revealed that the microbial diversity of secondary/persistent endodontic infections did not differ than those of primary endodontic infections. A new archaeal species, Candidatus Nitrosoarchaeum limnia, was detected in root canals of 1 patient with primary endodontic infection for the first time. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Microbial analysis in primary and persistent endodontic infections by using pyrosequencing.

    Science.gov (United States)

    Hong, Bo-Young; Lee, Tae-Kwon; Lim, Sang-Min; Chang, Seok Woo; Park, Joonhong; Han, Seung Hyun; Zhu, Qiang; Safavi, Kamran E; Fouad, Ashraf F; Kum, Kee Yeon

    2013-09-01

    The aim of this study was to investigate the bacterial community profile of intracanal microbiota in primary and persistent endodontic infections associated with asymptomatic chronic apical periodontitis by using GS-FLX Titanium pyrosequencing. The null hypothesis was that there is no difference in diversity of overall bacterial community profiles between primary and persistent infections. Pyrosequencing analysis from 10 untreated and 8 root-filled samples was conducted. Analysis from 18 samples yielded total of 124,767 16S rRNA gene sequences (with a mean of 6932 reads per sample) that were taxonomically assigned into 803 operational taxonomic units (3% distinction), 148 genera, and 10 phyla including unclassified. Bacteroidetes was the most abundant phylum in both primary and persistent infections. There were no significant differences in bacterial diversity between the 2 infection groups (P > .05). The bacterial community profile that was based on dendrogram showed that bacterial population in both infections was not significantly different in their structure and composition (P > .05). The present pyrosequencing study demonstrates that persistent infections have as diverse bacterial community as primary infections. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  6. Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus

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    Daniele Freitas Henriques

    2012-08-01

    Full Text Available Rocio virus (ROCV is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus. The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR. The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC. ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

  7. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

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    Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

    2013-11-21

    The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

  8. MONITORING OF CASES WITH A CHRONIC PERSISTENT INFECTION WITH HELICOBACTER PYLORI

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    Miglena Stamboliyska

    2014-09-01

    Full Text Available Introduction: The patients with persistent forms of Helicobacter pylori (HP infection are refractory to eradication treatment. They receive unsuccessful therapies, experience frequent recurrences and re-infections. One of the main reasons for the development of persistent forms is an inadequate and insufficient treatment. The persistent forms of HP infection create conditions for the maintenance of activity and for the progression of the induced chronic gastritis. In this aspect these cases will be at a higher risk for the development of gastric cancer. The aim of this study is: to monitor and analyze the cases with persistent HP infection and to establish an approach for their management. Clinical material and methods: The study includes 12 patients (8 female and 4 male at a middle age of 63,7, with a persistent HP infection, who have been observed for a period of five years. Two methods for the detection of HP infection are used – one invasive and one non-invasive. Upper endoscopy with morphological examination was performed. Results: In 9/12 patients HP was unsuccessfully treated for three times, in 2 patients – four times, and in 1 patient – five times. In all patients the initial treatment consisted of a standard triple therapy (STT. In 5 of them STT was conducted twice, with the same regimen for a period of seven days. Two patients received three courses of STT. In four patients an antibiotic resistance was established by means of a cultured assessment. In three cases an HP resistance to Clarithromycine and Metronidazole was demonstrated. Significant gastro-duodenal pathology with atrophic gastritis, intestinal metaplasia, and hyperplastic polyposis was found in all patients. The persistent clinical symptoms had 9 patients. Conclusion: We believe that a devised and proposed step strategy which covers early detection of infection, reliable diagnosis, adequate and successful treatment, and dispensary monitoring, contributes to the

  9. Mycobacterium avium-intracellulare infection during HIV disease. Persisting problems

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    Roberto Manfredi

    2008-12-01

    Full Text Available Still in the era of combined antiretroviral therapy, late recognition of HIV disease or lack of sufficient immune recovery pose HIV-infected patients at risk to develop opportunistic infections by nontuberculous mycobacteria (NTM, which are environmental organisms commonly retrieved in soil and superficial waters.Among these microorganisms, the most frequent is represented by Mycobacterium avium complex (MAC. Health care professionals who face HIV-infected patients should suspect disseminated mycobacterial disease when a deep immunodeficiency is present, (a CD4+ lymphocyte count below 50 cells/μL often associated with constitutional signs and symptoms, and non-specific laboratory abnormalities. Mycobacterial culture of peripheral blood is a reliable technique for diagnosing disseminated disease. Among drugs active against NTM, as well as some anti-tubercular compounds, the rifampin derivative rifabutin, and some novel fluoroquinolones, the availability of macrolides, has greatly contributed to improve both prophylaxis and treatment outcome of disseminated MAC infections. Although multiple questions remain about which regimens may be regarded as optimal, general recommendations can be expressed on the ground of existing evidences.Treatment should begin with associated clarithromycin (or azithromycin, plus ethambutol and rifabutin (with the rifabutin dose depending on other concomitant medications that might result in drug-drug interactions.A combined three-drug regimen is preferred for patients who cannot be prescribed an effective antiretroviral regimen immediately. Patients with a CD4+ lymphocyte count below 50 cells/μL, who do not have clinical evidence of active mycobacterial disease, should receive a primary prophylaxis with either clarithromycin or azithromycin, with or without rifabutin.

  10. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Nicholas D., E-mail: nweber@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: maubert@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: cdang@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: dstone2@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: kjerome@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  11. HAEMATOLOGICAL IMPACT OF NATURALLY OCCURING TICK BORNE HAEMOPARASITIC INFECTIONS IN CATTLE OF WEST BENGAL, INDIA

    Directory of Open Access Journals (Sweden)

    Apurba Debbarma

    2017-12-01

    Full Text Available Haemoparasites reduces productivity and may lead to high mortality among animals. The present study was carried out to evaluate the heamotological change in cattle of different districts in West Bengal, India affected with naturally occurring tick- borne haemoparasitic diseases (TBHD. A total of 310 cattle blood samples were screened for the presence of haemoparasites from July, 2015 to June, 2016. The blood samples were examined for haemoparasites by making thin blood smear and staining with Giemsa’s stain. The result showed that108 (34.84% cattle were found positive with TBHD, out of which 22.9% were Theileria sp, 5.8% were Babesia sp., 11.93% Anaplasma sp., and 5.8% were having mixed infection, respectively. The positive samples were subjected to estimations of haematological parameters i. e. Haemoglobin concentration (Hb, packed cell volume (PCV, total erythrocyte count (TEC and Total leucocytes count (TLC using standard protocol. The haematological analysis showed statistically a significant (p<0.01 decreased levels of Hb, PCV, TEC and TLC in infected groups of cattle compared to infection free group cattle. This is probably the first systematic report in West Bengal, India. The result showed the haemoparasites have a negative impact on haematological parameters. This study may be useful in disease epidemiological map preparation, parasitic control policy preparation of the study areas.

  12. No benefit of therapeutic vaccination in clinically healthy cats persistently infected with feline leukemia virus.

    Science.gov (United States)

    Helfer-Hungerbuehler, A Katrin; Spiri, Andrea M; Riond, Barbara; Grest, Paula; Boretti, Felicitas S; Hofmann-Lehmann, Regina

    2015-03-24

    Therapeutic vaccinations have a potential application in infections where no curative treatment is available. In contrast to HIV, efficacious vaccines for a cat retrovirus, feline leukemia virus (FeLV), are commercially available. However, the infection is still prevalent, and no effective treatment of the infection is known. By vaccinating persistently FeLV-infected cats and presenting FeLV antigens to the immune system of the host, e.g., in the form of recombinant and/or adjuvanted antigens, we intended to shift the balance toward an advantage of the host so that persistent infection could be overcome by the infected cat. Two commercially available FeLV vaccines efficacious in protecting naïve cats from FeLV infection were tested in six experimentally and persistently FeLV-infected cats: first, a canarypox-vectored vaccine, and second, an adjuvanted, recombinant envelope vaccine was repeatedly administered with the aim to stimulate the immune system. No beneficial effects on p27 antigen and plasma viral RNA loads, anti-FeLV antibodies, or life expectancy of the cats were detected. The cats were unable to overcome or decrease viremia. Some cats developed antibodies to FeLV antigens although not protective. Thus, we cannot recommend vaccinating persistently FeLV-infected cats as a means of improving their FeLV status, quality of life or life expectancy. We suggest testing of all cats for FeLV infection prior to FeLV vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Long-term persistence of oral human papillomavirus type 16: the HPV Infection in Men (HIM) study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Kreimer, Aimée R; Lin, Hui-Yi; Fulp, William; O'Keefe, Michael T; Ingles, Donna J; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2015-03-01

    Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. ©2015 American Association for Cancer Research.

  14. Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, Kirsten E; Thomsen, Louise T; Schmiedel, Sven

    2014-01-01

    Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithel...... intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection.......Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical...

  15. [Frequency of Candida in root canals of teeth with primary and persistent endodontic infections].

    Science.gov (United States)

    Bernal-Treviño, Angel; González-Amaro, Ana María; Méndez González, Verónica; Pozos-Guillen, Amaury

    2018-03-28

    Microbiological identification in endodontic infections has focused mainly on bacteria without giving much attention to yeasts, which, due to their virulence factors, can affect the outcomes of root canal treatment. To determine the frequency of Candida in anaerobic conditions in root canals with primary and persistent endodontic infection, as well as to evaluate a microbiological sampling method using aspiration compared to the traditional absorption method with paper points. Fifty microbiological samples were obtained from teeth of 47 patients requiring endodontic treatments, due to either primary or persistent infections. Two microbiological sampling methods were used: an aspiration method, and the traditional paper point absorption method. In each of these methods, two types of medium were used (M 1 -M 4 ). Samples were cultured under anaerobic conditions until reaching 0.5 McFarland turbidity, and then inoculated on Sabouraud dextrose, as well as on anaerobic enriched blood agar plates. Macroscopic and microscopic observations of the colonies were performed. The germ-tube test, growth on CHROMagar, and biochemical identification were performed on the isolated yeasts. Fungal infection was found in 18 (36%) samples out of the 50 teeth evaluated. In the 18 samples positive for fungal infection, 15 out of 36 (41.6%) teeth were taken from a primary infection, and 3 out of 14 (21.4%) from a persistent infection. The aspiration method using Sabouraud dextrose medium recovered a greater diversity of species. Yeasts frequency was higher in teeth with primary infections compared to teeth with persistent infections. The predominant yeast species was Candida albicans. The aspirating sampling method was more efficient in the recovery of Candida isolates than the traditional absorption method. Copyright © 2018 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

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    Marianne J. Middelveen

    2018-04-01

    Full Text Available Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

  17. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

    Science.gov (United States)

    Middelveen, Marianne J; Sapi, Eva; Burke, Jennie; Filush, Katherine R; Franco, Agustin; Fesler, Melissa C; Stricker, Raphael B

    2018-04-14

    Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi , in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

  18. An assessment of the long-term persistence of prion infectivity in aquatic environments

    International Nuclear Information System (INIS)

    Marín-Moreno, Alba; Espinosa, Juan-Carlos; Fernández-Borges, Natalia; Píquer, Juan; Girones, Rosina; Andreoletti, Olivier; Torres, Juan-María

    2016-01-01

    The environment plays a key role in horizontal transmission of prion diseases, since prions are extremely resistant to classical inactivation procedures. In prior work, we observed the high stability of bovine spongiform encephalopathy (BSE) infectivity when these prions were incubated in aqueous media such as phosphate-buffered saline (PBS) or wastewater for nearly nine months. As a continuation of this experiment, the same samples were maintained in PBS or wastewater for five additional years and residual BSE infectivity was assessed in bovine PrP C transgenic mice. Over this long time period (more than six years), BSE infectivity was reduced by three and one orders of magnitude in wastewater and PBS respectively. To rule out a possible agent specific effect, sheep scrapie prions were subjected to the same experimental protocol, using eight years as the experimental end-point. No significant reduction in scrapie infectivity was observed over the first nine months of wastewater incubation while PBS incubation for eight years only produced a two logarithmic unit reduction in infectivity. By contrast, the dynamics of PrP Res persistence was different, disappearing progressively over the first year. The long persistence of prion infectivity observed in this study for two different agents provides supporting evidence of the assumed high stability of these agents in aquatic environments and that environmental processes or conventional wastewater treatments with low retention times would have little impact on prion infectivity. These results could have great repercussions in terms of risk assessment and safety for animals and human populations. - Highlights: • Prion infectivity resists long term incubations in aquatic environments. • Infectivity persistence in wastewater is reduced when compared to PBS. • In this study PrPRes fails as a marker for prion detection. • Mice bioassay is the most powerful tool for assessing prion presence. • Wastewater conventional

  19. An assessment of the long-term persistence of prion infectivity in aquatic environments

    Energy Technology Data Exchange (ETDEWEB)

    Marín-Moreno, Alba; Espinosa, Juan-Carlos; Fernández-Borges, Natalia; Píquer, Juan [Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar S/n, Valdeolmos, 28130 Madrid (Spain); Girones, Rosina [Department of Microbiology, University of Barcelona, Diagonal 643, 08028 Barcelona (Spain); Andreoletti, Olivier [UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse (France); Torres, Juan-María, E-mail: jmtorres@inia.es [Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar S/n, Valdeolmos, 28130 Madrid (Spain)

    2016-11-15

    The environment plays a key role in horizontal transmission of prion diseases, since prions are extremely resistant to classical inactivation procedures. In prior work, we observed the high stability of bovine spongiform encephalopathy (BSE) infectivity when these prions were incubated in aqueous media such as phosphate-buffered saline (PBS) or wastewater for nearly nine months. As a continuation of this experiment, the same samples were maintained in PBS or wastewater for five additional years and residual BSE infectivity was assessed in bovine PrP{sup C} transgenic mice. Over this long time period (more than six years), BSE infectivity was reduced by three and one orders of magnitude in wastewater and PBS respectively. To rule out a possible agent specific effect, sheep scrapie prions were subjected to the same experimental protocol, using eight years as the experimental end-point. No significant reduction in scrapie infectivity was observed over the first nine months of wastewater incubation while PBS incubation for eight years only produced a two logarithmic unit reduction in infectivity. By contrast, the dynamics of PrP{sup Res} persistence was different, disappearing progressively over the first year. The long persistence of prion infectivity observed in this study for two different agents provides supporting evidence of the assumed high stability of these agents in aquatic environments and that environmental processes or conventional wastewater treatments with low retention times would have little impact on prion infectivity. These results could have great repercussions in terms of risk assessment and safety for animals and human populations. - Highlights: • Prion infectivity resists long term incubations in aquatic environments. • Infectivity persistence in wastewater is reduced when compared to PBS. • In this study PrPRes fails as a marker for prion detection. • Mice bioassay is the most powerful tool for assessing prion presence. • Wastewater

  20. HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

    Science.gov (United States)

    Serour, Y; Bendahmane, M; Abbou Baker, F; Medles, M; Moueddene, B; Kraiba, R

    2017-11-01

    Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Bárbara M. Schultz

    2018-05-01

    Full Text Available Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS and interleukin (IL-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2. Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

  2. Persistence of an SEIR Model with Immigration Dependent on the Prevalence of Infection

    Directory of Open Access Journals (Sweden)

    Wenjuan Wang

    2010-01-01

    Full Text Available We incorporate the immigration of susceptible individuals into an SEIR epidemic model, assuming that the immigration rate decreases as the spread of infection increases. For this model, the basic reproduction number, R0, is found, which determines that the disease is either extinct or persistent ultimately. The obtained results show that the disease becomes extinct as R01.

  3. Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) continues to have significant economic impact on the cattle industry worldwide. The virus is primarily maintained in the cattle population due to persistently infected animals. Herd surveillance along with good vaccination programs and biosecurity practices are the...

  4. Characteristics of Escherichia coli causing persistence or relapse of urinary tract infections

    DEFF Research Database (Denmark)

    Ejrnæs, Karen; Stegger, Marc; Reisner, Andreas

    2011-01-01

    Recurrent urinary tract infections (RUTIs) pose a major problem but little is known about characteristics of Escherichia coli associated with RUTI. This study includes E. coli from 155 women with community-acquired lower urinary tract infections (UTIs) randomized to one of three dosing regiments...... of persistence or relapse of UTI compared with three days. In vitro biofilm formation was not higher among E. coli causing persistence or relapse. The presence of agn43a(CFT073) or agn43b(CFT073) was associated with biofilm forming capacity. In conclusion, our results show potential targets for prevention...... and treatment of persistence/relapse of UTI and potential markers for selecting treatment lengths and warrant studies of these and new VFGs....

  5. A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

    2016-01-01

    immunodeficiency virus [SIV]) if its activity is not counteracted by the viral Vif protein. Here we investigate the ability of 7 naturally occurring variants of feline APOBEC3, APOBEC3Z3 (A3Z3), to inhibit FIV replication. Interestingly, one feline A3Z3 variant is dominant, restrictive, and naturally resistant to FIV Vif-mediated degradation. Phylogenetic analyses revealed that the ancestral change that generated this variant could have been caused by positive Darwinian selection, presumably due to an ancestral FIV infection. The experimental-phylogenetic investigation sheds light on the evolutionary history of the domestic cat, which was likely influenced by lentiviral infection. Copyright © 2015 Yoshikawa et al.

  6. Intracellular survival of Staphylococcus aureus during persistent infection in the insect Tenebrio molitor.

    Science.gov (United States)

    McGonigle, John E; Purves, Joanne; Rolff, Jens

    2016-06-01

    Survival of bacteria within host cells and tissues presents a challenge to the immune systems of higher organisms. Escape from phagocytic immune cells compounds this issue, as immune cells become potential vehicles for pathogen dissemination. However, the duration of persistence within phagocytes and its contribution to pathogen load has yet to be determined. We investigate the immunological significance of intracellular persistence within the insect model Tenebrio molitor, assessing the extent, duration and location of bacterial recovery during a persistent infection. Relative abundance of Staphylococcus aureus in both intracellular and extracellular fractions was determined over 21 days, and live S. aureus were successfully recovered from both the hemolymph and within phagocytic immune cells across the entire time course. The proportion of bacteria recovered from within phagocytes also increased over time. Our results show that to accurately estimate pathogen load it is vital to account for bacteria persisting within immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Megan C. Mladinich

    2017-07-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59 persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs, without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7, IRF9, and IFN-stimulated genes (ISGs 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

  8. Persistent proteinuria as an indicator of renal disease in HIV-infected children

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    Yuni Hisbiiyah

    2017-01-01

    Full Text Available Background Persistent proteinuria (microalbuminuria has been reported to be a precursor of HIV-related renal disease. Screening allows for early management in order to prevent the progression of renal disease and decrease morbidity and mortality associated with chronic kidney disease in HIV. Several studies have been done on renal manifestation in HIV-infected children from American and African regions, but similar studies from Asia are lacking. Objective To determine the prevalence of persistent proteinuria in HIV-positive children on antiretroviral therapy (ARV in Dr. Soetomo Hospital, Surabaya. Methods A cross-sectional study on children with HIV and treated with  highly active antiretroviral therapy (HARRT was done from August 2014 to February 2015. Microalbuminuria was measured by the ratio of urine albumin to creatinine (ACR, while proteinuria was measured by dipstick. Measurements were performed 3 times in 4-8 weeks. All subjects underwent complete evaluation of blood tests, serum creatinine, blood urea nitrogen (BUN, CD4 counts, and urinalysis. Data were analyzed using Chi-square and logistic regression tests. Results Of 38 children on HARRT enrolled in this study, 2 subjects developed acute kidney injury (AKI, 4 subjects were suspected to have urinary tract infection (UTI, and 1 subject was suspected to have urinary tract stones. The prevalence of persistent microalbuminuria was 2.6%. There was no correlation between immunological status, WHO clinical stage, or duration of ARV and the incidence of persistent proteinuria (P>0.05. Conclusion The prevalence of persistent proteinuria is  lower in younger HIV-infected children at a non-advanced stage and HIV-infected children with normal immunological status who are on HAART. We provide baseline data on the renal conditions of HIV-infected children in the era of HAART, before tenovofir is  increasingly used as an antiretroviral therapy regimen in Indonesia.

  9. Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

    Energy Technology Data Exchange (ETDEWEB)

    Kidwai, Afshan S.; Mushamiri, Ivy T.; Niemann, George; Brown, Roslyn N.; Adkins, Joshua N.; Heffron, Fred

    2013-08-12

    Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

  10. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

    Directory of Open Access Journals (Sweden)

    Brianna K. Swartwout

    2017-10-01

    Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  11. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

    Science.gov (United States)

    Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

    2017-10-13

    Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  12. Characterisation of a pestivirus isolated from persistently infected mousedeer (Tragulus javanicus)

    DEFF Research Database (Denmark)

    Grøndahl, C.; Uttenthal, Åse; Houe, Hans

    2003-01-01

    '-untranslated region and the E2 gene of pestivirus. The RT-PCR products were subsequently sequenced. Mousedeer A was positive in virus isolation on three occasions (days 1, 19 and 40) and by RT-PCR. The sister and mother of Mousedeer A were also found virus positive by isolation and RT-PCR. Mousedeer A, its...... of antibodies and the virus positive family members documented that the mousedeer were persistently infected with a pestivirus. The father of A probably had an acute infection resulting in antibodies to pestivirus and viral clearance. Sequence analysis and phylogenetic analysis revealed that the mousedeer...... pestivirus was closely related to BVDV Type 1f. The existences of persistently infected animals in non-domestic species have great implications for BVDV eradication campaigns in cattle....

  13. Hepatitis B virus DNA integration occurs early in the viral life cycle in an in vitro infection model via NTCP-dependent uptake of enveloped virus particles.

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A; Vondran, Florian W R; Shackel, Nicholas A; Urban, Stephan

    2018-02-07

    formation and persistence of virus infection. However, when and the mechanism(s) by which HBV DNA integration occurs is not clear. Here, we have developed and characterized an in vitro system to reliably detect HBV DNA integrations that result from a true HBV infection event and that closely resemble those found in patient tissues. Using this model, we show that integration already occurs when the infection is first established. Importantly, we provide here a system to analyze molecular factors involved in HBV integration, which can be used to develop strategies to halt its formation. Copyright © 2018 American Society for Microbiology.

  14. Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection

    Directory of Open Access Journals (Sweden)

    Sauder Christian

    2008-11-01

    Full Text Available Abstract Neonatal Borna disease virus (BDV infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats.

  15. Human Parechovirus 1 Infection Occurs via αVβ1 Integrin.

    Directory of Open Access Journals (Sweden)

    Pirjo Merilahti

    Full Text Available Human parechovirus 1 (HPeV-1 (family Picornaviridae is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to αVβ1, αVβ3 and αVβ6 integrin receptor(s, the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of αVβ1, αVβ3, αVβ6 and α5β1 in susceptible cell lines (A549, HeLa and SW480 to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express αVβ1 integrin but not αVβ3 or αVβ6 integrins. To further study the role of β1 integrin, we used a mouse cell line, GE11-KO, which is deficient in β1 expression, and its derivate GE11-β1 in which human integrin β1 subunit is overexpressed. HPeV-1 (Harris strain and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-β1 supported the internalization process. An integrin β1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with β1 integrin on the cell surface, and HPeV-1 and β1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of αVβ1 integrin without visible receptor clustering.

  16. Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle

    DEFF Research Database (Denmark)

    Hansen, K.R.; Nielsen, L.R.; Lind, Peter

    2006-01-01

    Aims: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. Methods...

  17. Generation of calves persistently infected with HoBi-like pestivirus and comparison of methods for detection of these persistent infections.

    Science.gov (United States)

    Bauermann, F V; Falkenberg, S M; Vander Ley, B; Decaro, N; Brodersen, B W; Harmon, A; Hessman, B; Flores, E F; Ridpath, J F

    2014-11-01

    The identification and elimination of persistently infected (PI) cattle are the most effective measures for controlling bovine pestiviruses, including bovine viral diarrhea virus (BVDV) and the emerging HoBi-like viruses. Here, colostrum-deprived calves persistently infected with HoBi-like pestivirus (HoBi-like PI calves) were generated and sampled (serum, buffy coat, and ear notches) on the day of birth (DOB) and weekly for 5 consecutive weeks. The samples were subjected to diagnostic tests for BVDV--two reverse transcriptase PCR (RT-PCR) assays, two commercial real-time RT quantitative PCR (RT-qPCR), two antigen capture enzyme-linked immunosorbent assays (ACE), and immunohistochemistry (IHC)--and to HoBi-like virus-specific RT-PCR and RT-qPCR assays. The rate of false negatives varied among the calves. The HoBi-like virus-specific RT-PCR detected HoBi-like virus in 83%, 75%, and 87% of the serum, buffy coat, and ear notch samples, respectively, while the HoBi-like RT-qPCR detected the virus in 83%, 96%, and 62%, respectively. In comparison, the BVDV RT-PCR test had a higher rate of false negatives in all tissue types, especially for the ear notch samples (missing detection in at least 68% of the samples). The commercial BVDV RT-qPCRs and IHC detected 100% of the ear notch samples as positive. While ACE based on the BVDV glycoprotein E(rns) detected infection in at least 87% of ear notches, no infections were detected using NS3-based ACE. The BVDV RT-qPCR, ACE, and IHC yielded higher levels of detection than the HoBi-like virus-specific assays, although the lack of differentiation between BVDV and HoBi-like viruses would make these tests of limited use for the control and/or surveillance of persistent HoBi-like virus infection. An improvement in HoBi-like virus tests is required before a reliable HoBi-like PI surveillance program can be designed. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  18. PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

    Science.gov (United States)

    Rositch, Anne F.; Koshiol, Jill; Hudgens, Michael; Razzaghi, Hilda; Backes, Danielle M.; Pimenta, Jeanne M.; Franco, Eduardo L.; Poole, Charles; Smith, Jennifer S.

    2013-01-01

    Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections. PMID:22961444

  19. Persistence of Tetracapsuloides bryosalmonae (Myxozoa) in chronically infected brown trout Salmo trutta.

    Science.gov (United States)

    Abd-Elfattah, Ahmed; Kumar, Gokhlesh; Soliman, Hatem; El-Matbouli, Mansour

    2014-08-21

    Proliferative kidney disease (PKD) is a widespread disease of farmed and wild salmonid populations in Europe and North America, caused by the myxozoan parasite Tetracapsuloides bryosalmonae. Limited studies have been performed on the epidemiological role in spread of the disease played by fish that survive infection with T. bryosalmonae. The aim of the present study was to evaluate the persistence of T. bryosalmonae developmental stages in chronically infected brown trout Salmo trutta up to 2 yr after initial exposure to laboratory-infected colonies of the parasite's alternate host, the bryozoan Fredericella sultana. Kidney, liver, spleen, intestine, brain, gills and blood were sampled 24, 52, 78 and 104 wk post-exposure (wpe) and tested for T. bryosalmonae by PCR and immunohistochemistry (IHC). Cohabitation trials with specific pathogen free (SPF) F. sultana colonies were conducted to test the viability of T. bryosalmonae. PCR detected T. bryosalmonae DNA in all tissue samples collected at the 4 time points. Developmental stages of T. bryosalmonae were demonstrated by IHC in most samples at the 4 time points. Cohabitation of SPF F. sultana with chronically infected brown trout resulted in successful transmission of T. bryosalmonae to the bryozoan. This study verified the persistence of T. bryosalmonae in chronically infected brown trout and their ability to infect the bryozoan F. sultana up to 104 wpe.

  20. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  1. Prolonged persistence of residual Wuchereria bancrofti infection after cessation of diethylcarbamazine-fortified salt programme.

    Science.gov (United States)

    Ramaiah, K D; Thiruvengadam, B; Vanamail, P; Subramanian, S; Gunasekaran, S; Nilamani, N; Das, P K

    2009-08-01

    A diethylcarbamazine (DEC)-fortified salt intervention programme was implemented between 1982 and 1986 in Karaikal district, Union territory of Pondicherry, south India, to control Culex transmitted bancroftian filariasis. The intervention reduced the microfilaria (Mf) rate from 4.49% to 0.08%. To eliminate the residual microfilaraemia, the health department detected and treated Mf carriers from 1987 to 2005 and mass-administered drugs in 2004 and 2005. Surveillance from 1987 to 2005 revealed persistent microfilaraemia in 0.03-0.42% of the population. In 2006, we conducted a more detailed Mf survey and a child antigenaemia (Ag) survey in 15 urban wards and 17 rural villages. These surveys showed an overall Mf rate of 0.46% in the high-risk urban areas and 0.18% in the rural areas; none of the sampled children was positive for Ag. All detected Mf carriers were >20 years old. The age of the youngest Mf carrier was 30 years in urban and 21 years in rural areas, which suggests that transmission was interrupted and there was no incidence of new Mf case after cessation of DEC salt programme. Eleven of 15 urban and 15 of 17 villages were totally free from microfilaraemia. Nevertheless, three of 15 surveyed urban localities and two of 17 villages showed >1% Mf rate. Thus, it seems that (i) post-intervention very low levels of microfilaraemia can continue as long as 20 years; (ii) 0.60-0.70% Mf rate is a safe level and at this level recrudescence of infection may not occur; (iii) there can be isolated localities with >1% Mf rate and their detection for further intervention measures could be challenging in larger control/elimination programmes and (iv) the residual infection mostly gets concentrated in the adult population, in underdeveloped urban areas and in historically highly endemic or large endemic rural areas. These groups and areas should be targeted with rigorous intervention measures such as mass drug administration to eliminate the residual infection.

  2. Evasion of short interfering RNA-directed antiviral silencing in Musa acuminata persistently infected with six distinct banana streak pararetroviruses.

    Science.gov (United States)

    Rajeswaran, Rajendran; Seguin, Jonathan; Chabannes, Matthieu; Duroy, Pierre-Olivier; Laboureau, Nathalie; Farinelli, Laurent; Iskra-Caruana, Marie-Line; Pooggin, Mikhail M

    2014-10-01

    Vegetatively propagated crop plants often suffer from infections with persistent RNA and DNA viruses. Such viruses appear to evade the plant defenses that normally restrict viral replication and spread. The major antiviral defense mechanism is based on RNA silencing generating viral short interfering RNAs (siRNAs) that can potentially repress viral genes posttranscriptionally through RNA cleavage and transcriptionally through DNA cytosine methylation. Here we examined the RNA silencing machinery of banana plants persistently infected with six pararetroviruses after many years of vegetative propagation. Using deep sequencing, we reconstructed consensus master genomes of the viruses and characterized virus-derived and endogenous small RNAs. Consistent with the presence of endogenous siRNAs that can potentially establish and maintain DNA methylation, the banana genomic DNA was extensively methylated in both healthy and virus-infected plants. A novel class of abundant 20-nucleotide (nt) endogenous small RNAs with 5'-terminal guanosine was identified. In all virus-infected plants, 21- to 24-nt viral siRNAs accumulated at relatively high levels (up to 22% of the total small RNA population) and covered the entire circular viral DNA genomes in both orientations. The hotspots of 21-nt and 22-nt siRNAs occurred within open reading frame (ORF) I and II and the 5' portion of ORF III, while 24-nt siRNAs were more evenly distributed along the viral genome. Despite the presence of abundant viral siRNAs of different size classes, the viral DNA was largely free of cytosine methylation. Thus, the virus is able to evade siRNA-directed DNA methylation and thereby avoid transcriptional silencing. This evasion of silencing likely contributes to the persistence of pararetroviruses in banana plants. We report that DNA pararetroviruses in Musa acuminata banana plants are able to evade DNA cytosine methylation and transcriptional gene silencing, despite being targeted by the host silencing

  3. Persistent renal cortical scintigram defects in children 2 years after urinary tract infection

    International Nuclear Information System (INIS)

    Ditchfield, Michael R.; Cook, David J.; Campo, John F. de; Grimwood, Keith; Powell, Harley R.; Gulati, Sanjeev; Sloane, Robert

    2004-01-01

    Background: Renal cortical scintigraphic studies challenge the role of vesicoureteric reflux in renal scar development, emphasizing instead the part played by acute pyelonephritis. Objective: To determine the prevalence of renal cortical defects in a child cohort 2 years after the child's first diagnosed urinary tract infection and to analyze the relationship of these defects with acute illness variables, primary vesicoureteric reflux and recurrent infections. Materials and methods: In a prospective cohort study, 193 children younger than 5 years with their first proven urinary tract infection underwent renal sonography, voiding cystourethrogram, and renal cortical scintigraphy within 15 days of diagnosis. Two years later, 150 of the 193 children, or 77.7%, had a further renal cortical scintigram, including 75, or 86.2%, of the 87 children who had acute scintigraphic defects. The relationship of cortical defects to age, gender, pre-treatment symptom duration, hospitalization, presence and grade of vesicoureteric reflux, and recurrent urinary tract infections was evaluated. Results: Overall, 20 of the 150 (13.3%; 95% confidence interval (CI) 8.3, 19.8) children had persistent defects 2 years after infection. This included 20 of 75 (26.7%; 95% CI 17.1, 38.1) with initially abnormal scintigrams. No new defects were detected. Although acute defects were more common in the young, those with persistent defects were older (median ages 16.4 vs. 6.8 months, P=0.004) than those with transient abnormalities. After adjustment for age, persistent defects were no longer associated with gender and were not predicted by acute illness variables, primary vesicoureteric reflux or recurrent infections. (orig.)

  4. Persistent and recurrent Trichomonas vaginalis infections: epidemiology, treatment and management considerations.

    Science.gov (United States)

    Seña, Arlene C; Bachmann, Laura H; Hobbs, Marcia M

    2014-06-01

    Trichomonas vaginalis (TV) is a common sexually transmitted infection that can cause vaginitis, cervicitis and urethritis. Persistent and recurrent TV infections are frequent in women, potentially due to the lack of routine screening recommendations for this pathogen, the chronic nature of some infections, and drug resistance. Metronidazole and tinidazole are two oral drugs that are effective against trichomoniasis. There are few alternative treatment options for persons with a metronidazole allergy or treatment failure. Most TV isolates from women with treatment failures that have been analyzed for susceptibility testing in the United States have exhibited low-level metronidazole resistance, supporting the initial use of tinidazole for patients who fail metronidazole therapy. Several non-nitroimidazole drugs and other agents have demonstrated acceptable in vitro activity or cure rates in case reports for metronidazole-resistant trichomoniasis; however, clinical trials are imperative to evaluate their efficacy as alternative therapeutic regimens for this highly prevalent infection.

  5. Aberrant cellular immune responses in humans infected persistently with parvovirus B19

    DEFF Research Database (Denmark)

    Isa, Adiba; Norbeck, Oscar; Hirbod, Taha

    2006-01-01

    A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study......, ex-vivo cellular immune responses were assessed by enzyme linked immunospot assay mounted against the majority of the translated viral genome. Compared to seropositive healthy individuals, individuals with B19 persistence (2-8 years) showed larger number of responses to the structural proteins (P = 0.......0022), whereas responses to the non-structural protein were of lower magnitude (P = 0.012). These observations provide the first findings of immunological discrepancies between individuals with B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion....

  6. Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

    Directory of Open Access Journals (Sweden)

    Receveur Marie-Catherine

    2009-12-01

    Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

  7. Biopsychosocial risk factors of persistent fatigue after acute infection: A systematic review to inform interventions.

    Science.gov (United States)

    Hulme, Katrin; Hudson, Joanna L; Rojczyk, Philine; Little, Paul; Moss-Morris, Rona

    2017-08-01

    Fatigue is a prevalent and debilitating symptom, preceded by an acute infectious episode in some patients. This systematic review aimed to identify risk factors for the development of persistent fatigue after an acute infection, to develop an evidence-based working model of post-infectious fatigue. Electronic databases (Medline, PsycINFO and EMBASE) were searched, from inception to March 2016, for studies which investigated biopsychosocial risk factors of on-going fatigue after an acute infection. Inclusion criteria were: prospective design; biological, psychological or social risk factors; standardised measure of post-infectious fatigue (self-report scales or clinical diagnosis). Studies were excluded if the sample had a pre-existing medical condition, infection was conceptualised as 'vaccination' or they were intervention trials. A narrative synthesis was performed. Eighty-one full texts were screened, of which seventeen were included in the review. Over half included glandular fever populations. Other infections included dengue fever, 'general'/'viral' and Q-fever. Risk factors were summarised under biological, social, behavioural, cognitive and emotional subthemes. Patients' cognitive and behavioural responses to the acute illness, and pre-infection or baseline distress and fatigue were the most consistent risk factors for post-infectious fatigue. An empirical summary model is provided, highlighting the risk factors most consistently associated with persistent fatigue. The components of the model, the possible interaction of risk factors and implications for understanding the fatigue trajectory and informing preventative treatments are discussed. Copyright © 2017. Published by Elsevier Inc.

  8. Impact of Persistent Intracellular Infections on the Processes of Airway Remodeling in Children with Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    O.Ye. Chernyshova

    2015-03-01

    Full Text Available The article presents information about the impact of persistent intracellular infections on the processes of airway remodeling in bronchial asthma in children. The influence of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, antibodies to type III collagen, endothelin-1 on the processes of morphological reconstruction of the airway by way of smooth muscle hypertrophy, enhanced neovascularization, epithelial cell hyperplasia, collagen deposition, thickening of the basal membrane, observed in bronchial asthma in children, were described.

  9. Polymorphisms in CISH gene are associated with persistent hepatitis B virus infection in Han Chinese population.

    Science.gov (United States)

    Hu, Zhangyong; Yang, Jinliang; Wu, Yangping; Xiong, Guolian; Wang, Yali; Yang, Jun; Deng, Lan

    2014-01-01

    Cytokine-inducible SRC homology 2 domain protein (CISH) is the first member of the suppressors of cytokine signaling (SOCS) protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs) in CISH gene with different outcomes of Hepatitis B virus (HBV) infection. 1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300) in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system. At position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300) showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (pCISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.

  10. Polymorphisms in CISH gene are associated with persistent hepatitis B virus infection in Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Zhangyong Hu

    Full Text Available BACKGROUND AND AIM: Cytokine-inducible SRC homology 2 domain protein (CISH is the first member of the suppressors of cytokine signaling (SOCS protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs in CISH gene with different outcomes of Hepatitis B virus (HBV infection. METHODS: 1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300 in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system. RESULTS: At position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300 showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (p<0.001. CONCLUSION: Two SNPs (rs414171 and rs2239751 in the CISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.

  11. Occurence of pregnancies among HIV infected Indian women : Does knowledge about HIV status make a difference?

    NARCIS (Netherlands)

    Darak, Shrinivas; Hutter, Inge; Kulkarni, Sanjeevani; Kulkarni, Vinay; Janssen, Fanny

    2015-01-01

    This is the first study to examine the behavioural effect of HIV on fertility among HIV infected women in India. Retrospective calendar data from ever-married HIV infected women between 15 and 45 years of age, attending a specialized HIV clinic in Pune, Western India (N = 560), were analysed.

  12. Frequency of the Occurence of Methicilin Resistant Staphylococcus aureus (MRSA Infections in Hyderabad, Pakistan

    Directory of Open Access Journals (Sweden)

    Nazir Ahmed Brohi

    2017-06-01

    Full Text Available Staphylococcus aureus is a potential pathogen of hospital and community related infections. It secretes toxins or the enzymes as virulence factor of mild to severe infections and show resistance to beta-lactam antibiotic including penicillin, methicillin, oxacillin and now vancomycin that could alarm of equal risk factors of Methicillin Resistant Staphylococcus aureus (MRSA infections in the patients. The survey report of 381 patients of Hyderabad, Pakistan was collected from March 2013 to June 2014 in which 176 cases were reported for Staphylococcus aureus in both genders of different age groups of 3-15 y kids, 16-45 y adults and 45-70 y olds, which showed 208 and 132 specimens Staphylococcus infection and 16 and 4 cases of MRSA infections in male and female patients, respectively whereas other 31 cases showed no infection. The laboratory diagnosis of the 200 samples from various hospitalized patients revealed the highest percentage of Methicillin Resistant Staphylococcus aureus MRSA in pus and post-operative wounds (17% followed by skin swabs (10%, sputum (7% and blood (0%. The observations revealed greater prevalence of MRSA infection in elderly age 16-45 years males than the females and other age groups. Antibiotic susceptibility test of 26 antibiotics revealed resistance (R-53%, sensitive (S-39 and variable (V-7% sensitivity zones (mm. Amplification of mecA gene was done using PCR reaction that revealed mecA gene bands up to 150-200 base pairs by test resistant strains.

  13. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence

    DEFF Research Database (Denmark)

    Kjær, Susanne K; Frederiksen, Kirsten; Plum, Christian Edinger Munk

    2010-01-01

    Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection...

  14. Quantitative molecular viral loads in 7 horses with naturally occurring equine herpesvirus-1 infection.

    Science.gov (United States)

    Estell, K E; Dawson, D R; Magdesian, K G; Swain, E; Laing, S T; Siso, S; Mapes, S; Pusterla, N

    2015-11-01

    Data associating quantitative viral load with severity, clinical signs and survival in equine herpesvirus-1 myeloencephalopathy (EHM) have not been reported. To report the clinical signs, treatment, and temporal progression of viral loads in 7 horses with naturally occurring EHM and to examine the association of these factors with survival. Retrospective case series. The population included 7 horses with EHM presented to the University of California, Davis William R. Pritchard Veterinary Medical Teaching Hospital from May to September 2011. Horses were graded using a neurological grading scale. Daily quantitative PCR was performed on nasal secretions and whole blood. Treatment, survival, outcome and histopathology were reported. At presentation, one horse was neurological grade 5/5, 3 were grade 4/5 and 3 were grade 3/5. All were treated with anti-inflammatory drugs, valacyclovir and management in a sling if necessary. All were infected with equine herpesvirus-1 of DNA polymerase D752 genotype. Peak viral load in nasal secretions and blood of 5 survivors ranged from 6.9 × 10(3) to 2.81 × 10(5) (median 5.11 × 10(4) ) and from 143 to 4340 gB gene copies/million eukaryotic cells (median 3146), respectively. The 2 nonsurvivors presented with grade 3/5 neurological signs and progressed to encephalopathy. Peak viral load was higher in nonsurvivors, with levels in nasal secretions of 1.9 × 10(9) and 2.2 × 10(9) and in blood of 2.05 × 10(4) and 1.02 × 10(5) gB gene copies/million eukaryotic cells. Case fatality was 2/7. Nonsurvivors had viral loads 1000-fold higher in nasal secretions and 10-fold higher in blood than survivors. There was no relationship between severity of clinical signs at presentation and survival. Thus, encephalopathy and high viral load were negatively associated with survival in this population. Further research should be performed to determine whether high viral loads are associated with encephalopathy and poor prognosis. The Summary is

  15. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection.

    Directory of Open Access Journals (Sweden)

    Lynn Soong

    2016-08-01

    Full Text Available Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d. inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi, followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF, as well as modulatory cytokines (IL-9, IL-13. Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions.

  16. Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice.

    Science.gov (United States)

    Bernhards, R C; Cote, C K; Amemiya, K; Waag, D M; Klimko, C P; Worsham, P L; Welkos, S L

    2017-03-01

    Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3-180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.

  17. Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

    DEFF Research Database (Denmark)

    Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.

    2007-01-01

    Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3·2 (95% CI...

  18. Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

    Directory of Open Access Journals (Sweden)

    Alec J Hirsch

    2017-03-01

    Full Text Available Zika virus (ZIKV, an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

  19. The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature.

    Science.gov (United States)

    Taylor, Sylvia; Bunge, Eveline; Bakker, Marina; Castellsagué, Xavier

    2016-06-14

    Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy. Not applicable, as systematic review of the literature.

  20. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    2010-08-01

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  1. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Frederikke F Rönsholt

    Full Text Available The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART.Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin.HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls.Discrete signs of systemic and vascular inflammation persist even after very long term cART.

  2. Acute and persistent Mycobacterium tuberculosis infections depend on the thiol peroxidase TpX.

    Directory of Open Access Journals (Sweden)

    Yanmin Hu

    Full Text Available The macrophage is the natural niche of Mycobacterium tuberculosis infection. In order to combat oxidative and nitrosative stresses and persist in macrophages successfully, M. tuberculosis is endowed with a very efficient antioxidant complex. Amongst these antioxidant enzymes, TpX is the only one in M. tuberculosis with sequence homology to thiol peroxidase. Previous reports have demonstrated that the M. tuberculosis TpX protein functions as a peroxidase in vitro. It is the dominant antioxidant which protects M. tuberculosis against oxidative and nitrosative stresses. The level of the protein increases in oxidative stress. To determine the roles of tpx gene in M. tuberculosis survival and virulence in vivo, we constructed an M. tuberculosis strain lacking the gene. The characteristics of the mutant were examined in an in vitro stationary phase model, in response to stresses; in murine bone marrow derived macrophages and in an acute and an immune resistant model of murine tuberculosis. The tpx mutant became sensitive to H(2O(2 and NO compared to the wild type strain. Enzymatic analysis using bacterial extracts from the WT and the tpx mutant demonstrated that the mutant contains reduced peroxidase activity. As a result of this, the mutant failed to grow and survive in macrophages. The growth deficiency in macrophages became more pronounced after interferon-gamma activation. In contrast, its growth was significantly restored in the macrophages of inducible nitric oxide synthase (iNOS or NOS2 knockout mice. Moreover, the tpx mutant was impaired in its ability to initiate an acute infection and to maintain a persistent infection. Its virulence was attenuated. Our results demonstrated that tpx is required for M. tuberculosis to deal with oxidative and nitrosative stresses, to survive in macrophages and to establish acute and persistent infections in animal tuberculosis models.

  3. Transcriptome markers of viral persistence in naturally-infected andes virus (bunyaviridae seropositive long-tailed pygmy rice rats.

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    Corey L Campbell

    Full Text Available Long-tailed pygmy rice rats (Oligoryzomys longicaudatus are principal reservoir hosts of Andes virus (ANDV (Bunyaviridae, which causes most hantavirus cardiopulmonary syndrome cases in the Americas. To develop tools for the study of the ANDV-host interactions, we used RNA-Seq to generate a de novo transcriptome assembly. Splenic RNA from five rice rats captured in Chile, three of which were ANDV-infected, was used to generate an assembly of 66,173 annotated transcripts, including noncoding RNAs. Phylogenetic analysis of selected predicted proteins showed similarities to those of the North American deer mouse (Peromyscus maniculatus, the principal reservoir of Sin Nombre virus (SNV. One of the infected rice rats had about 50-fold more viral burden than the others, suggesting acute infection, whereas the remaining two had levels consistent with persistence. Differential expression analysis revealed distinct signatures among the infected rodents. The differences could be due to 1 variations in viral load, 2 dimorphic or reproductive differences in splenic homing of immune cells, or 3 factors of unknown etiology. In the two persistently infected rice rats, suppression of the JAK-STAT pathway at Stat5b and Ccnot1, elevation of Casp1, RIG-I pathway factors Ppp1cc and Mff, and increased FC receptor-like transcripts occurred. Caspase-1 and Stat5b activation pathways have been shown to stimulate T helper follicular cell (TFH development in other species. These data are also consistent with reports suggestive of TFH stimulation in deer mice experimentally infected with hantaviruses. In the remaining acutely infected rice rat, the apoptotic pathway marker Cox6a1 was elevated, and putative anti-viral factors Abcb1a, Fam46c, Spp1, Rxra, Rxrb, Trmp2 and Trim58 were modulated. Transcripts for preproenkephalin (Prenk were reduced, which may be predictive of an increased T cell activation threshold. Taken together, this transcriptome dataset will permit rigorous

  4. Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection

    NARCIS (Netherlands)

    ten Brinke, A.; van Dissel, J. T.; Sterk, P. J.; Zwinderman, A. H.; Rabe, K. F.; Bel, E. H.

    2001-01-01

    Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. We investigated the annual loss of lung function in relation to seropositivity

  5. Enteric Infections occuring during an eight Year Period at the Chicago Zoological Park Brookfield, Illinois

    NARCIS (Netherlands)

    Williamson, W.M.; Tilden, E.B.; Getty, R.E.

    1963-01-01

    The bacteriological examinations of abnormal stools, irrespective of the apparent seriousness of the illness, is particularly important in a zoological park where it is difficult to apply measures to keep out possibly infected wild, non-resident animals and mechanical carriers, such as flies,

  6. Persistent anemia in a kidney transplant recipient with parvovirus B19 infection

    Directory of Open Access Journals (Sweden)

    Abbas Pakkyara

    2017-01-01

    Full Text Available Anemia after kidney transplant is not uncommon. This paper reports a case of unexplained anemia in a kidney transplant recipient that persisted for more than two months, and that did not respond to recombinant human erythropoietin treatment but was successfully treated after diagnosing Parvovirus B19 (ParvoV B19 infection. A middle-aged male underwent living-unrelated kidney transplantation from Pakistan in April 2015. He was on triple immuno-suppression therapy consisting of prednisolone, tacrolimus, and mycophenolate mofetil. He presented with anemia which persisted for more than two months that did not improve with Darbepoetin alpha and required blood transfusions. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts characteristic of a ParvoV B19 infection. The serum was highly positive for ParvoV B19 DNA polymerase chain reaction. The anemia resolved completely three weeks after the administration of intravenous immunoglobulin. ParvoV B19 infection should be considered in the differential diagnosis of kidney transplant recipients who present with anemia associated with a low reticulocyte count.

  7. Intraspecies Competition for Niches in the Distal Gut Dictate Transmission during Persistent Salmonella Infection

    Science.gov (United States)

    Lam, Lilian H.; Monack, Denise M.

    2014-01-01

    In order to be transmitted, a pathogen must first successfully colonize and multiply within a host. Ecological principles can be applied to study host-pathogen interactions to predict transmission dynamics. Little is known about the population biology of Salmonella during persistent infection. To define Salmonella enterica serovar Typhimurium population structure in this context, 129SvJ mice were oral gavaged with a mixture of eight wild-type isogenic tagged Salmonella (WITS) strains. Distinct subpopulations arose within intestinal and systemic tissues after 35 days, and clonal expansion of the cecal and colonic subpopulation was responsible for increases in Salmonella fecal shedding. A co-infection system utilizing differentially marked isogenic strains was developed in which each mouse received one strain orally and the other systemically by intraperitoneal (IP) injection. Co-infections demonstrated that the intestinal subpopulation exerted intraspecies priority effects by excluding systemic S. Typhimurium from colonizing an extracellular niche within the cecum and colon. Importantly, the systemic strain was excluded from these distal gut sites and was not transmitted to naïve hosts. In addition, S. Typhimurium required hydrogenase, an enzyme that mediates acquisition of hydrogen from the gut microbiota, during the first week of infection to exert priority effects in the gut. Thus, early inhibitory priority effects are facilitated by the acquisition of nutrients, which allow S. Typhimurium to successfully compete for a nutritional niche in the distal gut. We also show that intraspecies colonization resistance is maintained by Salmonella Pathogenicity Islands SPI1 and SPI2 during persistent distal gut infection. Thus, important virulence effectors not only modulate interactions with host cells, but are crucial for Salmonella colonization of an extracellular intestinal niche and thereby also shape intraspecies dynamics. We conclude that priority effects and

  8. Cytokine responses in acute and persistent human parvovirus B19 infection

    DEFF Research Database (Denmark)

    Isa, A; Lundqvist, A; Lindblom, A

    2007-01-01

    The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...... immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident...... at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response...

  9. HoBi-like pestivirus experimental infection in pregnant ewes: Reproductive disorders and generation of persistently infected lambs.

    Science.gov (United States)

    Decaro, Nicola; Losurdo, Michele; Larocca, Vittorio; Lucente, Maria Stella; Mari, Viviana; Varello, Katia; Patruno, Giovanni; Camero, Michele; Sciarra, Marina; Occhiogrosso, Leonardo; Tempesta, Maria; Iulini, Barbara; Buonavoglia, Canio

    2015-08-05

    In order to evaluate sheep as experimental model to test the efficacy of HoBi-like pestivirus vaccines for cattle, 10 sheep at different stages of pregnancy (30 or 50 days) were experimentally infected with the Italian prototype isolate Italy-1/10-1. Irrespective of the stage of pregnancy, virus inoculation resulted in reproductive failures, consisting of abortion, stillbirths or birth of weak or persistently infected (PI) lambs. Aborted fetuses, stillborn and dead lambs displayed extensive histopathological changes, consisting of hemorrhages, congestion and mononuclear infiltration in major organs. Pestiviral antigens were detected by immunohistochemistry in most tissues with remarkable signals in lungs and kidneys. PI lambs were constantly viremic, shed the virus through the nasal secretions and feces and, in all cases but one, did not have detectable HoBi-like pestivirus antibodies before the assumption of colostrum. The single seropositive infected lamb showed low-titer viremia and viral shedding that ceased only several weeks after the 3-month observation period. The study proves that sheep are susceptible to the reproduction failures caused by HoBi-like pestivirus infection and can serve as a suitable model for the evaluation of the fetal protection induced by homologous experimental vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Does Nasal Carriage of Staphylococcus aureus Increase the Risk of Postoperative Infections After Elective Spine Surgery: Do Most Infections Occur in Carriers?

    Science.gov (United States)

    Adogwa, Owoicho; Vuong, Victoria D; Elsamadicy, Aladine A; Lilly, Daniel T; Desai, Shyam A; Khalid, Syed; Cheng, Joseph; Bagley, Carlos A

    2018-05-14

    Wound infections after adult spinal deformity surgery place a high toll on patients, providers, and the healthcare system. Staphylococcus aureus is a common cause of postoperative wound infections, and nasal colonization by this organism may be an important factor in the development of surgical site infections (SSIs). The aim is to investigate whether post-operative surgical site infections after elective spine surgery occur at a higher rate in patients with methicillin-resistant S. aureus (MRSA) nasal colonization. Consecutive patients undergoing adult spinal deformity surgery between 2011-2013 were enrolled. Enrolled patients were followed up for a minimum of 3 months after surgery and received similar peri-operative infection prophylaxis. Baseline characteristics, operative details, rates of wound infection, and microbiologic data for each case of post-operative infection were gathered by direct medical record review. Local vancomycin powder was used in all patients and sub-fascial drains were used in the majority (88%) of patients. 1200 operative spine cases were performed for deformity between 2011 and 2013. The mean ± standard deviation age and body mass index were 62.08 ± 14.76 years and 30.86 ± 7.15 kg/m 2 , respectively. 29.41% had a history of diabetes. All SSIs occurred within 30 days of surgery, with deep wound infections accounting for 50% of all SSIs. Of the 34 (2.83%) cases of SSIs that were identified, only 1 case occurred in a patient colonized with MRSA. Our study suggests that the preponderance of SSIs occurred in patients without nasal colonization by methicillin-resistant S. aureus. Future prospective multi-institutional studies are needed to corroborate our findings. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

    Science.gov (United States)

    Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy

    2017-11-15

    Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  12. Fusarium musae infected banana fruits as potential source of human fusariosis: May occur more frequently than we might think and hypotheses about infection

    Science.gov (United States)

    Triest, David; Piérard, Denis; De Cremer, Koen; Hendrickx, Marijke

    2016-01-01

    ABSTRACT The banana fruit infecting fungus Fusarium musae was originally known as a distinct population within Fusarium verticillioides. However, recently, Fusarium musae was installed as a separate species and the first cases of human infection associated with Fusarium musae were found. In this article, we report an additional survey indicating that human pathogenic Fusarium musae infections may occur more frequently than we might think. Moreover, we evaluate the hypotheses on how infection can be acquired. A first hypothesis is that banana fruits act as carriers of Fusarium musae spores and thereby be the source of human infection with Fusarium musae. Acquisition is likely to be caused through contact with Fusarium musae contaminated banana fruits, either being imported or after traveling of the patient to a banana-producing country. An alternative hypothesis is that Fusarium musae is not only present on banana fruits, but also on other plant hosts or environmental sources. PMID:27195070

  13. Trichomonas vaginalis infection: How significant is it in men presenting with recurrent or persistent symptoms of urethritis?

    Science.gov (United States)

    Ng, Andrea; Ross, Jonathan D C

    2016-01-01

    Persistent or recurrent non-gonococcal urethritis has been reported to affect up to 10-20% of men attending sexual health clinics. An audit was undertaken to review the management of persistent or recurrent non-gonococcal urethritis in men presenting at Whittall Street Clinic, Birmingham, UK. Detection of Trichomonas vaginalis infection was with the newly-introduced nucleic acid amplification test. A total of 43 (8%) of 533 men treated for urethritis re-attended within three months with persistent or recurrent symptoms. Chlamydia trachomatis infection was identified in 13/40 (33%), T. vaginalis in 1/27 (4%) and Mycoplasma genitalium in 6/12 (50%). These findings suggest that the prevalence of T. vaginalis infection remains low in our clinic population and may not contribute significantly to persistent or recurrent non-gonococcal urethritis. © The Author(s) 2015.

  14. Comparison of detection of BVDV antigen in various types of tissue and fluid samples collected from persistently infected cattle

    Science.gov (United States)

    Aim. Bovine viral diarrhea viruses (BVDV) are economically important pathogens of cattle. Most new acute infections of BVDV are acquired from an animal persistently infected (PI) with BVDV. Surveillance programs typically rely on blood or skin biopsies for detection of PI cattle. PI animals have ...

  15. Temporal dynamics of ‘HoBi’-like pestivirus quasispecies in persistently infected calves generated under experimental conditions

    Science.gov (United States)

    ‘HoBi’-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up t...

  16. Synthetic AAV/CRISPR vectors for blocking HIV-1 expression in persistently infected astrocytes.

    Science.gov (United States)

    Kunze, Christine; Börner, Kathleen; Kienle, Eike; Orschmann, Tanja; Rusha, Ejona; Schneider, Martha; Radivojkov-Blagojevic, Milena; Drukker, Micha; Desbordes, Sabrina; Grimm, Dirk; Brack-Werner, Ruth

    2018-02-01

    Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes. Analysis of AAV9P1 transduction efficiencies with single brain cell populations, including primary human brain cells, as well as human brain organoids demonstrated that AAV9P1 targeted terminally differentiated human astrocytes much more efficiently than neurons. We then investigated whether AAV9P1 can be used to deliver HIV-inhibitory genes to astrocytes. To this end we generated AAV9P1 vectors containing genes for HIV-1 proviral editing by CRISPR/Cas9. Latently HIV-1 infected astrocytes transduced with these vectors showed significantly diminished reactivation of proviruses, compared with untransduced cultures. Sequence analysis identified mutations/deletions in key HIV-1 transcriptional control regions. We conclude that AAV9P1 is a promising tool for gene delivery to astrocytes and may facilitate inactivation/destruction of persisting HIV-1 proviruses in astrocyte reservoirs. © 2017 Wiley Periodicals, Inc.

  17. Infected Textiloma, 35 Years after the Operation for Femur Fracture, an extermly rare occurance.

    Science.gov (United States)

    Sadeghifar, Amir R; Saeed, Ali R

    2013-09-01

    Retained gauze after surgery is an uncommon error and it may be associated with many complications. We are reporting our case to call attention to the fact that retained gauze may become symptomatic even after a very long interval. Herein we report on a patient who developed infection and fistula with discharge from this error 35 years after a surgery for femur fracture and insertion of a IM nail. The diagnosis was easily made because of a marker in the gauze. Removal of the gauze and irrigation and debridement of the wound in two stages led to complete recovery of the patient as was shown in the 1 year follow up. Retained gauze after surgery is a preventable complication and may be asymptomatic for a very long period, but can become a complication post-operatively at any time. Hence, if diagnosed immediately after the surgery or at any other time, the gauze should be removed.

  18. Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

    Directory of Open Access Journals (Sweden)

    Bedeković Tomislav

    2011-12-01

    Full Text Available Abstract Background Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus Pestivirus, within the family Flaviviridae. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described. Findings Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells. Conclusions Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.

  19. Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

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    Ana Cristina Cisne Frota

    Full Text Available Abstract Objective: HIV-infected individuals (HIVI are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA after a meningococcal C conjugate (MCC vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU, aged 2–18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4 at baseline and at 12–18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02. 85 HIVI (44% had undetectable viral load (UVL. Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12–18 months after immunization (p = 0.14. Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2–766.6; UVL at entry (OR: 2.87, 95% CI: 0.96–8.62 and lower family income (OR: 0.09, 95% CI: 0.01–0.69 were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

  20. Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease

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    Elguezabal Natalia

    2012-06-01

    Full Text Available Abstract Background Inflammatory Bowel Disease (IBD, which includes both Crohn’s disease (CD and ulcerative colitis (UC, is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP. NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2% compared to CD patients (21.38% and UC patients (19.04% and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6% compared to the Basque CD cohort (15.5%, differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually

  1. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence.

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    Borel, Nicole; Dumrese, Claudia; Ziegler, Urs; Schifferli, Andrea; Kaiser, Carmen; Pospischil, Andreas

    2010-07-27

    Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 microm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

  2. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

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    Kaiser Carmen

    2010-07-01

    Full Text Available Abstract Background Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Results Infected cultures were investigated by immunofluorescence (IF, transmission electron microscopy (TEM and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs, medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. Conclusions In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

  3. OCCURENCE OF FUSARIUM HEAD BLIGHT OF WHEAT IN SLOVAKIA UNDER THE NATURAL INFECTION

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    Kamil Hudec

    2013-09-01

    Full Text Available Occurrence of Fusarium head blight FHB was documented during two consecutive years in June 2011 2012 under the natural conditions in winter wheat Triticum aestivum L. Observations were conducted at six different localities in four climatic regions in Slovakia. Incidence and severity of FHB were evaluated at the end of flowering stage in three replications. Each replication contained 100 spikes. These data served as a basis for FHB index calculations. Obtained FHB index values indicated that the environmental conditions of the year 2011 were more favourable to the development of FHB infection. Higher FHB index values were reached at localities with precipitation higher than 100% of long-term average. Although significantly higher incidence of heads with FHB symptoms was recorded in climatic region 02 quite warm, dry, hilly, correlation between the climatic regions was not confirmed. Except of the climatic conditions, the FHB development can be influenced by nitrogen application. The highest levels of FHB index was in coincidence with the highest and the lowest nitrogen rates applied. In all other cases, the effect of the mineral nutrition on head blight attack was unclear. Analyses of nitrogen forms applied revealed that nitrogen forms had no impact on FHB index value.

  4. The diagnosis and prevalence of persistent infection with bovine viral diarrhoea virus in South African feedlot cattle

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    Thelma Meiring

    2011-08-01

    Full Text Available Bovine viral diarrhoea virus (BVDV infection is an important viral infection affecting the cattle industry today. The prevalence of this infection in South African feedlots is unknown. Ear notch biopsies were collected from chronic poor doers and animals that appeared unthrifty upon entering feedlots, as well as animals entering the hospital pen with respiratory disease for the first time. A total of 1690 samples were collected: 1074 from the former category and 616 from the latter. A routine immunohistochemistry staining protocol showed that 49 animals tested positive, of which 43 (4% came from the feedlot entry group and six (1% from the hospitalised group. The prevalence of persistently infected cattle from this selected, nonrandom sample entering six large South African feedlots was found to be 2.9%, which is higher than the international rule of thumb that 0.5% of all cattle entering feedlots are persistently infected. There was no clear correlation between persistent infection and respiratory disease. Serum samples were also collected when possible and 10 positive cases were found. Results from enzyme-linked immunosorbent assays for antigen and antibody performed on these sera correlated well with those from the immunohistochemistry staining method in six cases, but in four cases the animals tested falsely positive owing to nonspecific staining. Immunohistochemistry staining on ear notch biopsies is thus a reliable diagnostic method to identify persistently infected animals with BVDV, but the pathologist should be aware of nonspecific positive staining.

  5. THE IMPACT OF PERSISTENT HERPESVIRUS INFECTION ON IMMUNITY AND VACCINATION RESPONSE

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    Volyanskiy AYu

    2016-09-01

    Full Text Available In this review we summarize current knowledge on the ability of latent herpesviruses to modulate the immunity and response to vaccination. Nearly all humans are latently infected with multiple herpesviruses but little is known about virus-host interactions. Meanwhile, the study of the immune response to Epshtein-Barr virus (EBV and сytomegalovirus (CMV has revealed significant regulatory effects on the immune system. During the primary infection a human cytomegalovirus is predominately found in peripheral blood monocytes and polymorphonuclear leukocytes. However, the virus can not be replicated in these cells. CMV induces the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral replication and the release of virions, which infect CD34+ myeloid progenitor cells. CMV latently persists in myeloid progenitor cells and monocytes and reactivates during their differentiation into macrophages. CMV-infected monocytes exhibit a unique reprogramming of their differentiation and secret both pro-inflammatory M1- and anti-inflammatory M2-associated cytokines. But cytomegalovirus induced macrophage phenotype skewed towards pro-inflammatory M1 type. MV has profound effects on the composition and function of both T cells and NK cells. CMV constantly reactivates during differentiation of monocytes into macrophages. Consequently, persons with latent CMV infection have substantially increased numbers and proportions of CD8+ T cells that lead to exhaustion and an early onset of immunosenescence. Also, it has been shown that the latent CMV virus infection markedly increases the proportion of NK cells expressing the activating NKG2C receptor. So, it has been proposed that CMV alters the composition of T cell and NK cell subsets and accelerates immune aging. Given the capacity of CMV to alter a macrophage, as well as NK and T cell responses it is reasonable to hypothesize that latent infection would alter the

  6. Colpocytological abnormalities in HIV infected and uninfected pregnant women: prevalence, persistence and progression.

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    Carriero, Carmine; Fascilla, Fabiana Divina; Cramarossa, Paola; Lepera, Achiropita; Bettocchi, Stefano; Vimercati, Antonella

    2018-02-01

    In this retrospective case-control study, we analyse data of 48 HIV-positive pregnant patients, versus a control group of 99 HIV-negative pregnant women, followed as outpatients by our department from 2009 to 2014. The aims of the study were to investigate the prevalence, persistence and progression of cervical squamous intraepithelial lesions (SIL) in each group and to correlate colpo-cytological lesions to the socio-demographic and clinical-laboratory findings in the HIV + pregnant women. In our study we observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions. Pap smear and colposcopy should be part of routine care for HIV-infected pregnant women because these lesions behave aggressively in these patients. Success of prevention depends on massive access of patients to screening. HAART reduces viral load and maintains CD4 count and can affect progression of SIL. Multidisciplinary services on the same site appear to be one promising strategy to improve compliance in patients. Impact Statement What is already known on this subject: Our study provided novel information on a highly vulnerable population of young HIV + pregnant women. What the results of this study add: We observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions remarkable with colposcopy. We could consider these important risk factors to evaluate to establish an appropriate strategy of management for these patients. What the implications are of these findings for clinical practice and/or further research: Association of the risk between SIL presence and HIV and HPV infection also deserves additional investigation. We believe that Pap smears and colposcopies should be part of the routine care for HIV-infected women because these lesions behave particularly aggressively in these patients.

  7. Enhanced surveillance of Clostridium difficile infection occurring outside hospital, England, 2011 to 2013.

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    Fawley, Warren N; Davies, Kerrie A; Morris, Trefor; Parnell, Peter; Howe, Robin; Wilcox, Mark H

    2016-07-21

    There are limited national epidemiological data for community-associated (CA)-Clostridium difficile infections (CDIs). Between March 2011 and March 2013, laboratories in England submitted to the Clostridium difficile Ribotyping Network (CDRN) up to 10 diarrhoeal faecal samples from successive patients with CA-CDI, defined here as C. difficile toxin-positive diarrhoea commencing outside hospital (or less than 48 hours after hospital admission), including those cases associated with community-based residential care, with no discharge from hospital within the previous 12 weeks. Patient demographics and C. difficile PCR ribotypes were compared for CA-CDIs in our study and presumed healthcare-associated (HA) CDIs via CDRN. Ribotype diversity indices, ranking and relative prevalences were very similar in CA- vs HA-CDIs, although ribotypes 002 (p ≤ 0.0001),020 (p = 0.009) and 056 (p < 0.0001) predominated in CA-CDIs; ribotype 027 (p = 0.01) predominated in HA-CDIs. Epidemic ribotypes 027 and 078 predominated in institutional residents with CDI (including care/nursing homes) compared with people with CDI living at home. Ribotype diversity decreased with increasing age in HA-CDIs, but not in CA-CDIs. Ribotype 078 CA-CDIs were significantly more common in elderly people (3.4% (6/174) vs 8.7% (45/519) in those aged < 65 and ≥ 65 years, respectively; p = 0.019). No antibiotics were prescribed in the previous four weeks in about twofold more CA-CDI vs HAs (38.6% (129/334) vs 20.3% (1,226/6,028); p < 0.0001). We found very similar ribotype distributions in CA- and HA-CDIs, although a few ribotypes significantly predominated in one setting. These national data emphasise the close interplay between, and likely common reservoirs for, CDIs, particularly when epidemic strains are not dominant. This article is copyright of The Authors, 2016.

  8. Polymerase chain reaction detection of Propionibacterium propionicus and Actinomyces radicidentis in primary and persistent endodontic infections.

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    Siqueira, José F; Rôças, Isabela N

    2003-08-01

    persistent endodontic infections. This strengthens the assumption that this bacterial species is an endodontic pathogen associated with different forms of periradicular diseases. In contrast, A radicidentis was only occasionally detected in the patients examined. The role played by this species in endodontic infections remains to be clarified.

  9. Comparison of Detection of Bovine Virus Diarrhea Virus Antigen in Various Types of Tissue and Fluid Samples Collected from Persistently Infected Cattle

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    Bovine viral diarrhea viruses are economically important pathogens of cattle. Most new infections are acquired from animals persistently infected with the virus. Surveillance programs rely on skin biopsies for detection of persistently infected cattle. The purpose of this study was to compare ant...

  10. Nutritional rehabilitation of persistent diarrhea in childhood : Factors determining recovery and the relationship of systemic infections with intestinal function

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    Bhutta, Zulfiqar Ahmed

    1996-01-01

    Nutritional rehabilitation of persistent diarrhea in childhood: factors determining recovery and the relationship of systemic infections with intestinal function Zulfiqar A. Bhutta Nutritional rehabilitation of persistent diarrhea (PD), a major killer of children in the third world, poses an enormous challenge. We validated the efficacy of a traditional local weaning diet based on rice-lentils (Khitchri) and yogurt (K-Y diet) for nutritional rehabilitation of PD. ...

  11. Mucosal disease-like syndrome in a calf persistently infected by Hobi-like pestivirus.

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    Decaro, Nicola; Lanave, Gianvito; Lucente, Maria Stella; Mari, Viviana; Varello, Katia; Losurdo, Michele; Larocca, Vittorio; Bozzetta, Elena; Cavaliere, Nicola; Martella, Vito; Buonavoglia, Canio

    2014-08-01

    A calf persistently infected with Hobi-like pestivirus displayed severe clinical signs and subsequently died. Gross lesions and histopathological changes were suggestive of hemorrhagic and necrotic inflammation involving several tissues. A Hobi-like pestivirus pair was isolated from the dead calf, i.e., cytopathogenic (CP) and noncytopathogenic (NCP) strains strictly related to each other and to Italian prototype isolates at the genetic level. Two biotype-specific real-time reverse transcription-PCR assays determined the time of the emergence of the CP virus as 1 month before the calf's death. This highest RNA titers were reached in lymphoid and nervous system tissues, whereas only traces of CP viral RNA were found in blood. In contrast, great NCP virus loads were present in all tissues and biological fluids. The present report provides new insights into the pathogenesis and molecular mechanisms of this emerging group of pestiviruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Management of persistent periapical infection on maxillary lateral incisorby apex resection of: A case report

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    Yusri Yusri

    2016-06-01

    Full Text Available Endodontic failure can be caused by different etiology, one of them is a persistent periapical infection in the root canal system. If the endodontic convensional retreatment is difficult to be done, surgical endodontic will be recomended. Endodontic surgical can eliminate the causative agent of periradicular disease and to restore the biological condition of periodontium and functional. A 22 years old male patient came to the Dental Hospital Hasanuddin University at Tamalanrea with the chief complaint is discomfort of the left maxillary lateral incisor. Radiograph examinations showed radiolucency 4 mm of tooth 22. The diagnosis is chronic apical periodontitis.Three month after endodontic conventional, the patients complaint is settled. Extended care plan will be treated is apex resection. The purpose of this case report is to present the treatment protocol of apex resection on  the maxillary left lateral incisor.

  13. Understanding the impact of infection, inflammation and their persistence in the pathogenesis of bronchopulmonary dysplasia

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    Jherna eBalany

    2015-12-01

    Full Text Available The concerted interaction of genetic and environmental factors act on the preterm human immature lung with inflammation being the common denominator leading to the multifactorial origin of the most common chronic lung disease in infants – bronchopulmonary dysplasia or BPD. Adverse perinatal exposure to infection/inflammation with added insults like invasive mechanical ventilation, exposure to hyperoxia and sepsis causes persistent immune dysregulation. In this review article we have attempted to analyze and consolidate current knowledge about the role played by persistent prenatal and postnatal inflammation in the pathogenesis of BPD. While some parameters of the early inflammatory response (neutrophils, cytokines etc. may not be detectable after days to weeks of exposure to noxious stimuli, they have already initiated the signaling pathways of the inflammatory process / immune cascade and have affected permanent defects structurally and functionally in the BPD lungs. Hence translational research aimed at prevention / amelioration of BPD needs to focus on dampening the inflammatory response at an early stage to prevent the cascade of events leading to lung injury with impaired healing resulting in the pathologic pulmonary phenotype of alveolar simplification and dysregulated vascularization characteristic of BPD.

  14. Investigations of significance of vaccination against swine parvovirosis in persistently infected sows

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    Lupulović Diana

    2007-01-01

    Full Text Available Parvoviral infection of swine is a disease which is manifested in reproductive disorders in sows and gilts in the form of anestria, premature births, miscarriages, mummified fetuses, the birth of poorly vital piglets and/or a reduced number of piglets in the litter. The infection is present in farms with intensive breeding conditions in the form of an endemic infection, all over the world, and also in our country. Timely diagnostics and adequate prophylaxis prevent the occurrence and spread of this disease. Experimental investigations covered 21 sows, divided into two experimental and a third, the control, group. Animals of the first experimental group were vaccinated once before exposure to the boar using an inactivated vaccine, Porcilis Parvo, and animals of the second experimental group were vaccinated twice at an interval of 3 weeks, also using an inactivated vaccine, Parvovax. Sows of the control group were not vaccinated. Blood samples were taken from all animals four times during the course of the experiment, and specific antibodies against the swine parvovirus were determined using the method of hemagglutination inhibition (HI test. The results of the investigations indicate that there was an increase in the titre of specific antibodies following the vaccination of persistently infected sows with the swine parvivirus, and that the present antibodies did not prevent the creating of an immune response. It was established following a comparison of the geometric mean values of antibody titres of vaccinated sows that there was a significant increase in the antibody level following the two vaccinations using the Parvovax vaccine, against the titre values in sows vaccinated once with the Porcilis Parvo vaccine. In control animals, the average value of the antibody level was many times lower in comparison with the established values in the experimental groups. This provides justification for the implementation of immunoprophylaxis against swine

  15. Human T cell aging and the impact of persistent viral infections

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    Tamas eFulop

    2013-09-01

    Full Text Available Aging is associated with a dysregulation of the immune response, loosely termed immunosenescence. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV, which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

  16. Examination of the inventory of drug use consequences with individuals with serious and persistent mental illness and co-occurring substance use disorders.

    Science.gov (United States)

    Bennett, Melanie E; Nidecker, Melissa; Strong Kinnaman, Joanna E; Li, Lan; Bellack, Alan S

    2009-01-01

    The Inventory of Drug Use Consequences (InDUC) ( [1] ) is a 50-item measure that evaluates lifetime and recent consequences of substance use. This study examined the psychometric properties of a modified version of the Inventory of Drug Use Consequences (InDUC-M) in individuals with serious and persistent mental illness (SPMI) and co-occurring substance use disorders (SUDs). We examined self-reported consequences in the sample, evaluated internal consistency, identified items for a brief form of the InDUC-M, and explored relationships with indicators of substance use severity. InDUC-M Lifetime and Recent subscales showed good internal consistency and were related to other measures of substance use and problems. A brief version of the InDUC-M Recent (SIP-M) showed excellent internal consistency and was highly correlated with both Lifetime and Recent subscales. The InDUC-M and the SIP-M performed well in individuals with SPMI and SUDs. Overall, these findings are a useful first step in determining the utility of the InDUC-M in people with SPMI and SUDs.

  17. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

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    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  18. Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions.

    Science.gov (United States)

    Weber, Matheus N; Bauermann, Fernando V; Canal, Cláudio W; Bayles, Darrell O; Neill, John D; Ridpath, Julia F

    2017-01-02

    'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. An increase in genetic variability and the development of certain mutations was observed over time. Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. Published by Elsevier B.V.

  19. Cost of Care for HIV-Infected Patients with Co-Occurring Substance Use Disorder or Psychiatric Disease: Report from a Large, Integrated Health Plan

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    Gerald N. DeLorenze

    2014-01-01

    Full Text Available Background. The costs of providing care to HIV-infected (HIV+ patients with co-occurring diagnoses of substance use (SU disorder or psychiatric disease (PD are not well documented. It is our objective to evaluate costs in these HIV+ patients receiving care in a large health plan. Methods. We conducted a retrospective cohort study from 1995 to 2010 to compare costs of healthcare in HIV+ patients with and without co-occurring SU disorder and/or PD diagnoses. Estimates of proportional differences in costs (rate ratios were obtained from repeated measures generalized linear regression. Models were stratified by cost category (e.g., inpatient, outpatient. Results. Mean total healthcare costs per patient per year were higher in HIV+ patients diagnosed with SU disorder or PD compared to HIV+ patients without these comorbid conditions. After controlling for confounders, total mean costs remained significantly higher in patients diagnosed with SU disorder (RR = 1.24, 95% CI = 1.18–1.31 or PD (RR = 1.19, 95% CI = 1.15–1.24. Mean outpatient care costs were significantly greater in patients with both SU disorder and PD (RR = 1.52, 95% CI = 1.41–1.64. Conclusions. Given these higher expenditures in the care of HIV+ patients with comorbid SU disorder and/or PD, greater efforts to facilitate SU disorder or PD treatment initiation and persistence could provide substantial savings.

  20. Congenital infection with atypical porcine pestivirus (APPV) is associated with disease and viral persistence.

    Science.gov (United States)

    Schwarz, Lukas; Riedel, Christiane; Högler, Sandra; Sinn, Leonie J; Voglmayr, Thomas; Wöchtl, Bettina; Dinhopl, Nora; Rebel-Bauder, Barbara; Weissenböck, Herbert; Ladinig, Andrea; Rümenapf, Till; Lamp, Benjamin

    2017-01-06

    In 2013, several Austrian piglet-producing farms recorded outbreaks of action-related repetitive myoclonia in newborn piglets ("shaking piglets"). Malnutrition was seen in numerous piglets as a complication of this tremor syndrome. Overall piglet mortality was increased and the number of weaned piglets per sow decreased by more than 10% due to this outbreak. Histological examination of the CNS of affected piglets revealed moderate hypomyelination of the white substance in cerebellum and spinal cord. We detected a recently discovered pestivirus, termed atypical porcine pestivirus (APPV) in all these cases by RT-PCR. A genomic sequence and seven partial sequences were determined and revealed a 90% identity to the US APPV sequences and 92% identity to German sequences. In confirmation with previous reports, APPV genomes were identified in different body fluids and tissues including the CNS of diseased piglets. APPV could be isolated from a "shaking piglet", which was incapable of consuming colostrum, and passaged on different porcine cells at very low titers. To assess the antibody response a blocking ELISA was developed targeting NS3. APPV specific antibodies were identified in sows and in PCR positive piglets affected by congenital tremor (CT). APPV genomes were detected continuously in piglets that gradually recovered from CT, while the antibody titers decreased over a 12-week interval, pointing towards maternally transmitted antibodies. High viral loads were detectable by qRT-PCR in saliva and semen of infected young adults indicating a persistent infection.

  1. Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

    Directory of Open Access Journals (Sweden)

    Sally N. Adebamowo

    2017-06-01

    Full Text Available BackgroundRecent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections.MethodsWe examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections.ResultsThe mean (SD age of the study participants was 38 (8 years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01. Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008, compared to women who were negative for both.ConclusionWe found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed

  2. Persistent Bovine Viral Diarrhea Virus infection in domestic and wild small ruminants and camelids including the mountain goat (Oreamnos americanus

    Directory of Open Access Journals (Sweden)

    Danielle Darracq Nelson

    2016-01-01

    Full Text Available Bovine viral diarrhea virus (BVDV is a Pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus.

  3. Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

    OpenAIRE

    Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R.; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

    2015-01-01

    The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by...

  4. Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.

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    Loïc Coutte

    2009-02-01

    Full Text Available Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained "template-independent" sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.

  5. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis Infections in Men With Nongonococcal Urethritis: Predictors and Persistence After Therapy

    Science.gov (United States)

    Seña, Arlene C.; Lensing, Shelly; Rompalo, Anne; Taylor, Stephanie N.; Martin, David H.; Lopez, Laureen M.; Lee, Jeannette Y.; Schwebke, Jane R.

    2012-01-01

    Background. Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU). We assessed their predictors and persistence after treatment. Methods. We analyzed data from an NGU treatment trial among symptomatic heterosexual men aged 16–45 years from STI clinics. Nucleic acid amplification tests detected CT, MG, and TV at baseline and at 1 and 4 weeks after therapy. Associations between variables and STI detection were investigated. Results. Among 293 participants, 44% had CT, 31% had MG, and 13% had TV at baseline. In multivariate analysis, CT infection was associated with young age and STI contact. Young age was also associated with MG, and having ≥1 new partner was negatively associated with TV. We detected persistent CT in 12% and MG in 44% of participants at 4 weeks after therapy, which were associated with signs and symptoms of NGU. Persistent CT was detected in 23% of participants after azithromycin treatment vs 5% after doxycycline treatment (P = .011); persistent MG was detected in 68% of participants after doxycycline vs 33% after azithromycin (P = .001). All but 1 TV infection cleared after tinidazole. Conclusions. Persistent CT and MG after treatment of NGU are common, and were associated with clinical findings and drug regimen. PMID:22615318

  6. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study.

    Science.gov (United States)

    Nguyen, Thuy-Nhien; von Seidlein, Lorenz; Nguyen, Tuong-Vy; Truong, Phuc-Nhi; Hung, Son Do; Pham, Huong-Thu; Nguyen, Tam-Uyen; Le, Thanh Dong; Dao, Van Hue; Mukaka, Mavuto; Day, Nicholas Pj; White, Nicholas J; Dondorp, Arjen M; Thwaites, Guy E; Hien, Tran Tinh

    2018-05-01

    A substantial proportion of Plasmodium species infections are asymptomatic with densities too low to be detectable with standard diagnostic techniques. The importance of such asymptomatic plasmodium infections in malaria transmission is probably related to their duration and density. To explore the duration of asymptomatic plasmodium infections and changes in parasite densities over time, a cohort of participants who were infected with Plasmodium parasites was observed over a 2-year follow-up period. In this open cohort study, inhabitants of four villages in Vietnam were invited to participate in baseline and subsequent 3-monthly surveys up to 24 months, which included the collection of venous blood samples. Samples were batch-screened using ultra-sensitive (u)PCR (lower limit of detection of 22 parasites per mL). Participants found to be infected by uPCR during any of these surveys were invited to join a prospective cohort and provide monthly blood samples. We estimated the persistence of Plasmodium falciparum and Plasmodium vivax infections and changes in parasite densities over a study period of 24 months. Between Dec 1, 2013, and Jan 8, 2016, 356 villagers participated in between one and 22 surveys. These study participants underwent 4248 uPCR evaluations (11·9 tests per participant). 1874 (32%) of 4248 uPCR tests indicated a plasmodium infection; 679 (36%) of 1874 tests were P falciparum monoinfections, 507 (27%) were P vivax monoinfections, 463 (25%) were co-infections with P falciparum and P vivax, and 225 (12%) were indeterminate species of Plasmodium. The median duration of P falciparum infection was 2 months (IQR 1-3); after accounting for censoring, participants had a 20% chance of having parasitaemia for 4 months or longer. The median duration of P vivax infection was 6 months (3-9), and participants had a 59% chance of having parasitaemia for 4 months or longer. The parasite densities of persistent infections oscillated; following ultralow

  7. Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance.

    Science.gov (United States)

    Gebhardt, Thomas; Palendira, Umaimainthan; Tscharke, David C; Bedoui, Sammy

    2018-05-01

    A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T RM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T RM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T RM cells and tissue-resident lymphocytes. It is now widely appreciated that T RM cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 +  CD69 +  CD103 + T RM cells, we will review current concepts on the generation, persistence and function of T RM cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T RM responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. A built-in co-carcinogenic effect due to viruses involved in latent or persistent infections

    DEFF Research Database (Denmark)

    Hersoug, Lars-Georg; Arnau, José

    2007-01-01

    instability. Because of chromosomal instability, the genome of these cell lines will lead to changes from generation to generation and will face a remarkable selection pressure both from lost traits, apoptosis, and from the immune system. Viruses causing latent or persistent infections have evolved many...

  9. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  10. Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

    Science.gov (United States)

    Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

    2011-09-21

    Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

  11. CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN) in two preterm twin neonates.

    Science.gov (United States)

    Manzoni, Paolo; Vivalda, Mauro; Mostert, Michael; Priolo, Claudio; Galletto, Paolo; Gallo, Elena; Stronati, Mauro; Gili, Renata; Opramolla, Anna; Calabrese, Sara; Tavella, Elena; Luparia, Martina; Farina, Daniele

    2014-09-01

    The diagnosis of congenital CMV is usually guided by a number of specific symptoms and findings. Unusual presentations may occur and diagnosis is challenging due to uncommon or rare features. Here we report the case of two preterm, extremely low birthweight, 28-week gestational age old twin neonates with CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN). They were born to a HIV-positive mother, hence they underwent treatment with zidovudine since birth. Both infants featured severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support, with full recovery after 2 months. Treatment with ganciclovir was not feasible due the concomitant treatment with zidovudine and the risk of severe, fatal toxicity. Therefore administration of intravenous hyperimmune anti-CMV immunoglobulin therapy was initiated. Severe lung involvement at birth and subsequent pulmonary hypertension are rarely described in preterm infants as early manifestations of CMV congenital disease. In the two twin siblings here described, the extreme prematurity and the treatment with zidovudine likely worsened immunosuppression and ultimately required a complex management of the CMV-associated lung involvement. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection

    NARCIS (Netherlands)

    Rodrigo, Chaturaka; Walker, Melanie R.; Leung, Preston; Eltahla, Auda A.; Grebely, Jason; Dore, Gregory J.; Applegate, Tanya; Page, Kimberly; Dwivedi, Sunita; Bruneau, Julie; Morris, Meghan D.; Cox, Andrea L.; Osburn, William; Kim, Arthur Y.; Schinkel, Janke; Shoukry, Naglaa H.; Lauer, Georg M.; Maher, Lisa; Hellard, Margaret; Prins, Maria; Luciani, Fabio; Lloyd, Andrew R.; Bull, Rowena A.

    2017-01-01

    Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved

  13. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai 200063 (China); Liu, Siwen [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Bode, Liv [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Liu, Chengyu [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Zhang, Liang [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Xiao [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Li, Dan [Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Lei, Yang [Department of Internal Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 400016 (China); Peng, Xiaojun [Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou 310018 (China); Cheng, Zhongyi [Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092 (China); and others

    2015-11-15

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  14. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    International Nuclear Information System (INIS)

    Liu, Xia; Liu, Siwen; Bode, Liv; Liu, Chengyu; Zhang, Liang; Wang, Xiao; Li, Dan; Lei, Yang; Peng, Xiaojun; Cheng, Zhongyi

    2015-01-01

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  15. Prevalence and intensity of human soil transmitted helminth infections in the Akonolinga health district (Centre Region, Cameroon: Are adult hosts contributing in the persistence of the transmission?

    Directory of Open Access Journals (Sweden)

    Jean Bopda

    2016-06-01

    Conclusion: This study reveals that STH infections are prevalent in adults in the Akonolinga health district, with moderate to high risk and light intensity of infection. These infected adults might constitute a potential parasite reservoir and a source of dissemination and persistence of these infections, highlighting the need to really take into account this neglected group of individuals in the mass treatment policy.

  16. Effects of interferon-tau on cattle persistently infected with bovine viral diarrhea virus.

    Science.gov (United States)

    Kohara, Junko; Nishikura, Yumiko; Konnai, Satoru; Tajima, Motoshi; Onuma, Misao

    2012-08-01

    In this study, the antiviral effects of bovine interferon-tau (boIFN-tau) on bovine viral diarrhea virus (BVDV) were examined in vitro and in vivo. In the in vitro experiments, the replication of cytopathic and non-cytopathic BVDV was inhibited in the bovine cells treated with boIFN-tau. The replication of BVDV was completely suppressed by boIFN-tau at a concentration higher than 10(2) U/ml. In order to examine the effect of boIFN-tau on virus propagation in cattle persistently infected (PI) with non-cytopathic BVDV, boIFN-tau was subcutaneously administered to PI cattle at 10(5) U/kg or 10(6) U/kg body weight 5 times per week for 2 weeks. No physical abnormality such as depression was observed in the cattle during the experiment. The mean BVDV titers in the serum of the PI cattle decreased slightly during the boIFN-tau administration period with the dose of 10(6) U/kg. However, the BVDV titers in the serum returned to the pre-administration level after the final boIFN-tau administration. These results suggest that boIFN-tau demonstrates an anti-BVDV effect, reducing the BVDV level in serum transiently when injected into PI cattle.

  17. Increased Persistence of Initial Treatment for HIV Infection With Modern Antiretroviral Therapy.

    Science.gov (United States)

    Davy-Mendez, Thibaut; Eron, Joseph J; Zakharova, Oksana; Wohl, David A; Napravnik, Sonia

    2017-10-01

    Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used. An observational clinical cohort study in the Southeastern United States. All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models. One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI. Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure.

  18. Characterization of Sendai virus persistently infected L929 cells and Sendai virus pi strain: recombinant Sendai viruses having Mpi protein shows lower cytotoxicity and are incapable of establishing persistent infection

    International Nuclear Information System (INIS)

    Nishio, Machiko; Tsurudome, Masato; Ito, Morihiro; Kawano, Mitsuo; Komada, Hiroshi; Ito, Yasuhiko

    2003-01-01

    It is commonly accepted that the temperature-sensitive phenotype of Sendai virus (SeV) persistently infected cells is caused by the M and/or HN proteins. Expression level of the L, M, HN, and V proteins is extremely low in L929 cells persistently infected with SeVpi (L929/SeVpi cells) incubated at 38 deg. C. The HN protein quickly disappears in L929/SeVpi cells following a temperature shift up to 38 deg. C, and pulse-chase experiments show that the Lpi, HNpi, and Mpi proteins are unstable at 38 deg. C. Following a temperature shift either upward or downward, M protein is translocated into the nucleus and then localizes to the perinuclear region. None of virus-specific polypeptides are detected in the cells primarily infected with SeVpi and incubated at 38 deg. C and virus proteins are not pulse-labeled at 38 deg. C, indicating that temperature-sensitive step is at an early stage of infection. The Mpi protein is transiently located in the nucleus of the SeVpi primarily infected cells. Recombinant SeVs possessing the HNpi or/and Mpi proteins are not temperature-sensitive. The HN protein is expressed at very low levels and the F protein localizes to the perinuclear region in rSeV(Mpi)-infected cells incubated at 38 deg. C for 18 h. rSeVs having the Mpi protein exhibit lower cytotoxicity and are incapable of establishing persistent infection. Amino acid 116 of the Mpi protein is related to the nuclear translocation and lower cytopathogenesis, whereas aa183 is involved in the interaction between M protein and viral glycoproteins

  19. Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

    Science.gov (United States)

    Hu, Ke-Qin; Cui, Wei

    2018-05-01

    Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

  20. Comparison of ‘HoBi’-like viral populations among persistent infected calves generated under experimental conditions and to inoculum virus

    Science.gov (United States)

    Like other members from the Pestivirus genus, ‘HoBi’-like pestiviruses cause economic losses for cattle producers due to both acute and persistent infections. Pestivirus exist as quasispecies (swarms of individual viruses) in persistently infected (PI) animals leading to viral populations that are m...

  1. Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain

    DEFF Research Database (Denmark)

    Bukh, Jens; Thimme, Robert; Meunier, Jean-Christophe

    2008-01-01

    Protective immunity after resolved hepatitis C virus (HCV) infection has been reported. However, the breadth of this immunity has remained controversial, and the role of neutralizing antibodies has not been well-defined. In the present study, two chimpanzees (CH96A008 and CH1494) with resolved...... homologous rechallenges with monoclonal H77C or polyclonal H77 and after six heterologous rechallenges with HC-J4 (genotype 1b) or HC-J6 (genotype 2a) viruses. Subsequently, a final challenge with H77C resulted in persistent HCV infection. In both chimpanzees, serum neutralizing antibodies against retroviral...... of viruses recovered from CH1494 after the two homologous rechallenges that resulted in transient viremia were identical with the H77C virus. In contrast, the polyprotein sequences of viruses recovered from both chimpanzees after homologous rechallenge resulting in persistent infection had numerous changes...

  2. Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

    Science.gov (United States)

    Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

    2011-07-05

    Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

  3. A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Despite the availability of an effective vaccine, hepatitis B virus (HBV infection remains a major health problem. HBV e antigen (HBeAg-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA. The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection. Persistence of the HBeAg-negative infection was monitored at predetermined time points using HBV-specific markers including HBV surface antigen (HBsAg, HBeAg, and HBV core antigen (HBcAg as well as DNA copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage. HBsAg levels increased up to 1 week, at which point levels peaked and dropped quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more than 10 weeks. High numbers of HBV DNA copies were detected in the serum and liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected with HBeAg-negative HBV throughout the study period. These results demonstrate the first successful establishment of a model of HBeAg-negative HBV-persistent infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the infection persistence and levels of serum virological and biochemical markers were approximately equal in the model mice. This model will be useful for mechanistic studies on HBeAg-negative HBV infection and will facilitate the evaluation of new antiviral drugs.

  4. The fusion protein of wild-type canine distemper virus is a major determinant of persistent infection

    International Nuclear Information System (INIS)

    Plattet, Philippe; Rivals, Jean-Paul; Zuber, BenoIt; Brunner, Jean-Marc; Zurbriggen, Andreas; Wittek, Riccardo

    2005-01-01

    The wild-type A75/17 canine distemper virus (CDV) strain induces a persistent infection in the central nervous system but infects cell lines very inefficiently. In contrast, the genetically more distant Onderstepoort CDV vaccine strain (OP-CDV) induces extensive syncytia formation. Here, we investigated the roles of wild-type fusion (F WT ) and attachment (H WT ) proteins in Vero cells expressing, or not, the canine SLAM receptor by transfection experiments and by studying recombinants viruses expressing different combinations of wild-type and OP-CDV glycoproteins. We show that low fusogenicity is not due to a defect of the envelope proteins to reach the cell surface and that H WT determines persistent infection in a receptor-dependent manner, emphasizing the role of SLAM as a potent enhancer of fusogenicity. However, importantly, F WT reduced cell-to-cell fusion independently of the cell surface receptor, thus demonstrating that the fusion protein of the neurovirulent A75/17-CDV strain plays a key role in determining persistent infection

  5. Persistence of Antibodies to West Nile Virus in Naturally Infected Rock Pigeons (Columba livia)

    Science.gov (United States)

    Gibbs, Samantha E. J.; Hoffman, Douglas M.; Stark, Lillian M.; Marlenee, Nicole L.; Blitvich, Bradley J.; Beaty, Barry J.; Stallknecht, David E.

    2005-01-01

    Wild caught rock pigeons (Columba livia) with antibodies to West Nile virus were monitored for 15 months to determine antibody persistence and compare results of three serologic techniques. Antibodies persisted for the entire study as detected by epitope-blocking enzyme-linked immunosorbent assay and plaque reduction neutralization test. Maternal antibodies in squabs derived from seropositive birds persisted for an average of 27 days. PMID:15879030

  6. Factors Associated with the Risk of Persistent Gastrostomy Site Infection Following Laparoscopic or Open Nissen Fundoplication

    Directory of Open Access Journals (Sweden)

    Hisayuki Miyagi

    2017-01-01

    Full Text Available Background: Gastrostomy for feeding disorders or swallowing dysfunctions can be complicated by persistent gastrostomy site infection (PGSI. PGSI causes nutrient leakage, with dilated PGSI requiring gastrostomy reconstruction. The purpose of this study was to evaluate the causes, patient characteristics, and perioperative management of PGSI after Nissen fundoplication and gastrostomy for patients with gastro-oesophageal reflux. Patients and Methods: The records of all patients who underwent Nissen fundoplication and gastrostomy for gastro-oesophageal reflux over the past 12 years were retrieved. Risk factors were analysed, including age at surgery, gender, operative procedure, use of postoperative ventilator management, gastrostomy tube migration towards the pylorus, bacterial culture results, and length of hospital stay. PGSI as a cause of inflammation was analysed statistically. Results: Forty patients were identified, ranging in age from 1 to 49 years (median, 11 years surgically. Twenty each underwent laparoscopic and open surgery, with all undergoing gastrostomy using the Stamm technique. Four patients developed PGSI. Gastrostomy tubes had migrated postoperatively to the pyloric side in three of these four patients (P < 0.005, increasing intragastric pressure. Three of these four patients also required positive pressure ventilation during the perioperative period (P < 0.001. Conclusion: PGSI correlates with the perioperative management of positive pressure and with increased intragastric pressure resulting from pyloric obstruction, which is caused by aberrant distribution of the gastrostomy tube to the pyloric side. Statistical Analysis Used: Factors in the two groups were compared statistically by Mann–Whitney U-test to determine whether PGSI caused inflammation. Statistical significance was defined as P < 0.05.

  7. Naturally occurring Influenza A virus subtype H1N2 infection in a Midwest United States mink (Mustela vison) ranch.

    Science.gov (United States)

    Yoon, Kyoung-Jin; Schwartz, Kent; Sun, Dong; Zhang, Jianqiang; Hildebrandt, Hugh

    2012-03-01

    Influenza A virus (FLUAV) causes acute respiratory disease in humans and a variety of animal species. The virus tends to remain within the species of origin; nonetheless, naturally occurring cross-species transmission of FLUAV has been periodically documented. Multiple cross-species transmissions of FLUAV have been reported from companion animals and captive wild animals, neither of which is historically considered as natural hosts of FLUAV. In the fall of 2010, mink (Mustela vison) inhabiting a 15,000-head mink farm in the Midwest United States experienced persistent severe respiratory distress and nose and/or mouth bleeding. Mink losses averaged approximately 10 animals per day. Six dead mink at 6 months of age were submitted to the Iowa State University Veterinary Diagnostic Laboratory for diagnostic investigation. Gross and microscopic examinations revealed that all 6 mink had hemorrhagic bronchointerstitial pneumonia. Hemolytic Escherichia coli was isolated from lungs, probably accounting for hemorrhagic pneumonia. All animals tested negative for Canine distemper virus and Aleutian mink disease virus. Interestingly, FLUAV of H1N2 subtype, which contained the matrix gene of swine lineage, was detected in the lungs. Serological follow-up on mink that remained in the ranch until pelting also confirmed that the ranch had been exposed to FLUAV of H1 subtype (δ clade). The case study suggests that FLUAV should be included in the differential diagnosis when mink experience epidemics of respiratory disease. Since the source of FLUAV appeared to be uncooked turkey meat, feeding animals fully cooked ration should be considered as a preventive measure.

  8. Host-response to foot-and-mouth disease in cattle; possible implications for the development of persistently infected "carriers"

    DEFF Research Database (Denmark)

    Stenfeldt, Anna Carolina

    course of infection with FMDV O UKG 34/2001 in sheep. An experimental study design involving endoscopical collection of small biopsies of pharyngeal mucosa from live cattle was developed. This technique enables collection of sequential tissue samples from infected animals, allowing investigation...... the pharyngeal epithelia during early infection. Similar analyses were performed on samples of pharyngeal epithelia and associated lymph nodes collected during post mortem examinations performed at around 32-35 days post infection in order to investigate possible sites of virus persistence. The early host...... response to FMDV O in cattle was investigated through measurements of systemic parameters consisting of the acute phase proteins, serum amyloid A (SAA) and haptoglobin (HP), as well as type 1 interferon (IFN). The local tissue response within the pharyngeal epithelia was investigated through measurements...

  9. Persistent scrotal pain and suspected orchido-epididymitis of a young boy during pinworm (Enterobius vermicularis) infection in the bowel.

    Science.gov (United States)

    Sinikumpu, J-J; Serlo, W

    2011-08-01

    Pinworm (Enterobius vermicularis) is the most common parasite among mankind. Ectopic pinworm infections in number of organs are broadly reported. The aim of this report is to review the pinworm infection in the scrotum on the basis of our case. Our patient is a young boy with persistent pain in the scrotums together with abdominal symptoms. He underwent several urgent operations. Pinworm was finally found in appendix vermiformis. We hypothesize that concurrent unresponsive orchido-epididymitis was caused by pinworm as well. Eradication happened finally with pyvrinembonate. Pinworm is a parasite that lives usually in the bowel. Many ectopic locations, like scrotum, are known. Orchido-epididymitis by pinworm has to be kept in mind when treating boys with persistent scrotal pain. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  10. Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis

    International Nuclear Information System (INIS)

    Airaksinen, Antero; Pariente, Nonia; Menendez-Arias, Luis; Domingo, Esteban

    2003-01-01

    BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin

  11. Persistence and infectivity of Zika virus in semen after returning from endemic areas: Report of 5 cases.

    Science.gov (United States)

    García-Bujalance, S; Gutiérrez-Arroyo, A; De la Calle, F; Díaz-Menéndez, M; Arribas, Jose R; García-Rodríguez, J; Arsuaga, M

    2017-11-01

    There are limited data about the persistence and infectivity of Zika virus in semen of symptomatic travelers returning from endemic areas and even less data in asymptomatic cases. We investigated the persistence and infectivity of ZIKA virus in semen in five patients with Zika virus infection returning to Spain from endemic areas. We evaluated the epidemiological, clinical and virological characteristic of the five patients. In semen we detected ZIKA virus by PCR, partial sequencing and cell culture. We also performed phylogenetic analysis. We detected Zika virus RNA (Asian lineage) by PCR in semen samples from day 14th to day 96th since the day of illness onset. Semen viral culture was positive for Zika virus in two patients at days of illness 30 and 69 by virus propagation. Phylogenetic analysis strongly suggested male to female sexual transmission in a couple returning from Maldives. This case series confirms that Zika virus RNA can be detected in semen up to three months after infection. Viral culture of semen samples shows prolonged infectivity that can lead to sexual transmission of Zika virus. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Analysis of risk factors for persistent infection of asymptomatic women with high-risk human papilloma virus.

    Science.gov (United States)

    Shi, Nianmin; Lu, Qiang; Zhang, Jiao; Li, Li; Zhang, Junnan; Zhang, Fanglei; Dong, Yanhong; Zhang, Xinyue; Zhang, Zheng; Gao, Wenhui

    2017-06-03

    This study aims to prevent persistentinfection, reduce the incidence of cervical cancer, and improve women's health by understanding the theoretical basis of the risk factors for continuous infection of asymptomatic women with high-risk human papilloma virus (HPV) strains via information collected, which includes the persistent infection rate and the most prevalent HPV strain types of high risk to asymptomatic women in the high-risk area of cervical cancer in Linfen, Shanxi Province. Based on the method of cluster sampling, locations were chosen from the industrial county and agricultural county of Linfen, Shanxi Province, namely the Xiangfen and Quwo counties. Use of the convenience sampling (CS) method enables the identification of women who have sex but without symptoms of abnormal cervix for analyzing risk factors of HPV-DNA detection and performing a retrospective questionnaire survey in these 2 counties. Firstly, cervical exfoliated cell samples were collected for thin-layer liquid-based cytology test (TCT), and simultaneously testing high-risk type HPV DNA, then samples with positive testing results were retested to identify the infected HPV types. The 6-month period of testing was done to derive the 6-month persistent infection rate. The retrospective survey included concepts addressed in the questionnaire: basic situation of the research objects, menstrual history, marital status, pregnancy history, sexual habits and other aspects. The questionnaire was divided into a case group and a comparison group, which are based on the high-risk HPV-DNA testing result to ascertain whether or not there is persistent infection. Statistical analysis employed Epidate3.1 software for date entry, SPSS17.0 for date statistical analysis. Select statistic charts, Chi-Square Analysis, single-factor analysis and multivariate Logistic regression analysis to analyze the protective factors and risk factors of high-risk HPV infection. Risk factors are predicted by using the

  13. Deficient incorporation of spike protein into virions contributes to the lack of infectivity following establishment of a persistent, non-productive infection in oligodendroglial cell culture by murine coronavirus

    International Nuclear Information System (INIS)

    Liu Yin; Herbst, Werner; Cao Jianzhong; Zhang Xuming

    2011-01-01

    Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non-productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels.

  14. An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.

    Directory of Open Access Journals (Sweden)

    Makoto Ohashi

    2012-12-01

    Full Text Available Acute Epstein-Barr virus (EBV infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1 signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV, naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1. Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection.

  15. Therapeutic Antiviral Effect of the Nucleic Acid Polymer REP 2055 against Persistent Duck Hepatitis B Virus Infection

    Science.gov (United States)

    Noordeen, Faseeha; Scougall, Catherine A.; Grosse, Arend; Qiao, Qiao; Ajilian, Behzad B.; Reaiche-Miller, Georget; Finnie, John; Werner, Melanie; Broering, Ruth; Schlaak, Joerg F.; Vaillant, Andrew; Jilbert, Allison R.

    2015-01-01

    Previous studies have demonstrated that nucleic acid polymers (NAPs) have both entry and post-entry inhibitory activity against duck hepatitis B virus (DHBV) infection. The inhibitory activity exhibited by NAPs prevented DHBV infection of primary duck hepatocytes in vitro and protected ducks from DHBV infection in vivo and did not result from direct activation of the immune response. In the current study treatment of primary human hepatocytes with NAP REP 2055 did not induce expression of the TNF, IL6, IL10, IFNA4 or IFNB1 genes, confirming the lack of direct immunostimulation by REP 2055. Ducks with persistent DHBV infection were treated with NAP 2055 to determine if the post-entry inhibitory activity exhibited by NAPs could provide a therapeutic effect against established DHBV infection in vivo. In all REP 2055-treated ducks, 28 days of treatment lead to initial rapid reductions in serum DHBsAg and DHBV DNA and increases in anti-DHBs antibodies. After treatment, 6/11 ducks experienced a sustained virologic response: DHBsAg and DHBV DNA remained at low or undetectable levels in the serum and no DHBsAg or DHBV core antigen positive hepatocytes and only trace amounts of DHBV total and covalently closed circular DNA (cccDNA) were detected in the liver at 9 or 16 weeks of follow-up. In the remaining 5/11 REP 2055-treated ducks, all markers of DHBV infection rapidly rebounded after treatment withdrawal: At 9 and 16 weeks of follow-up, levels of DHBsAg and DHBcAg and DHBV total and cccDNA in the liver had rebounded and matched levels observed in the control ducks treated with normal saline which remained persistently infected with DHBV. These data demonstrate that treatment with the NAP REP 2055 can lead to sustained control of persistent DHBV infection. These effects may be related to the unique ability of REP 2055 to block release of DHBsAg from infected hepatocytes. PMID:26560490

  16. Diagnosis Of Persistent Infection In Prosthetic Two-Stage Exchange: PCR analysis of Sonication fluid From Bone Cement Spacers.

    Science.gov (United States)

    Mariaux, Sandrine; Tafin, Ulrika Furustrand; Borens, Olivier

    2017-01-01

    Introduction: When treating periprosthetic joint infections with a two-stage procedure, antibiotic-impregnated spacers are used in the interval between removal of prosthesis and reimplantation. According to our experience, cultures of sonicated spacers are most often negative. The objective of our study was to investigate whether PCR analysis would improve the detection of bacteria in the spacer sonication fluid. Methods: A prospective monocentric study was performed from September 2014 to January 2016. Inclusion criteria were two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Beside tissues samples and sonication, broad range bacterial PCRs, specific S. aureus PCRs and Unyvero-multiplex PCRs were performed on the sonicated spacer fluid. Results: 30 patients were identified (15 hip, 14 knee and 1 ankle replacements). At reimplantation, cultures of tissue samples and spacer sonication fluid were all negative. Broad range PCRs were all negative. Specific S. aureus PCRs were positive in 5 cases. We had two persistent infections and four cases of infection recurrence were observed, with bacteria different than for the initial infection in three cases. Conclusion: The three different types of PCRs did not detect any bacteria in spacer sonication fluid that was culture-negative. In our study, PCR did not improve the bacterial detection and did not help to predict whether the patient will present a persistent or recurrent infection. Prosthetic 2-stage exchange with short interval and antibiotic-impregnated spacer is an efficient treatment to eradicate infection as both culture- and molecular-based methods were unable to detect bacteria in spacer sonication fluid after reimplantation.

  17. Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

    Science.gov (United States)

    2013-01-01

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable. PMID:23675947

  18. Intermittent negative pressure wound therapy with instillation for the treatment of persistent periprosthetic hip infections: a report of two cases

    Directory of Open Access Journals (Sweden)

    Söylemez MS

    2016-02-01

    Full Text Available Mehmet Salih Söylemez,1 Korhan Özkan,2 Bülent Kılıç,3 Samet Erinç41Department of Orthopaedics and Traumatology, Bingöl State Hospital, Bingöl, 2Department of Orthopaedics and Traumatology, Faculty of Medicine, Medeniyet University, Istanbul, 3Department of Orthopaedics and Traumatology, Orthopaedic Surgery Clinic, Istanbul Gelişim University, Tekirdağ, 4Department of Orthopaedics and Traumatology, Istanbul Medeniyet University, Göztepe Training and Research Hospital, Istanbul, TurkeyAbstract: Intermittent negative pressure wound therapy with instillation (NPWTi is starting to be used successfully to treat early periprosthetic infections of endoprostheses. However, few articles have reported the outcome of treatment with intermittent NPWTi for late persistent periprosthetic infections of the hip. In this study, we report two cases who underwent several rounds of radical wound debridement for the treatment of a late persistent periprosthetic infection of the hip. Intermittent NPWTi was used in both cases. Patients were treated successfully and there was no recurrence after 3 and 1 years of follow-up, respectively.Keywords: negative pressure, vacuum-assisted, periprosthetic infection, hip

  19. Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats.

    Science.gov (United States)

    Bachofen, Claudia; Vogt, Hans-Rudolf; Stalder, Hanspeter; Mathys, Tanja; Zanoni, Reto; Hilbe, Monika; Schweizer, Matthias; Peterhans, Ernst

    2013-05-15

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.

  20. Persistent extraradicular infection in root-filled asymptomatic human tooth: scanning electron microscopic analysis and microbial investigation after apical microsurgery.

    Science.gov (United States)

    Signoretti, Fernanda G C; Endo, Marcos S; Gomes, Brenda P F A; Montagner, Francisco; Tosello, Fernanda B; Jacinto, Rogério C

    2011-12-01

    Procedural accidents have a negative effect on healing and might contribute to the persistence of infections in inaccessible apical areas, requiring surgical intervention. This report describes a case of persistent apical periodontitis of a lower left first molar associated with the sinus tract and a periapical lesion that required nonsurgical endodontic retreatment and apical surgery for resolution. The tooth had received endodontic treatment 3 years ago and had to be retreated using the crown-down technique with chemical auxiliary substance (2% chlorhexidine gel), foramen patency, and enlargement and was filled in a single appointment. The occlusal access cavity was immediately restored with composite resin. After 1 month, it could be observed that the sinus tract persisted and, radiographically, the lesion remained unaltered. Therefore, endodontic microsurgery was indicated. Apical microsurgery was performed under magnification with the use of a dental operating microscope including apicectomy, root end with ultrasound, and sealing with mineral trioxide aggregate. A microbiological sample was collected from the apical lesion. The resected distal root apex was observed by scanning electron microscopy. The following species were detected: Actinomyces naeslundii and Actinomyces meyeri, Propionibacterium propionicum, Clostridium botullinum, Parvimonas micra, and Bacteroides ureolyticus; scanning electron microscopic analysis revealed bacterial biofilm surrounding the apical foramen and external radicular surface. Gutta-percha overfilling at the apex because of a zip caused during initial endodontic treatment could be observed. A 6-month follow-up showed apparent radiographic periapical healing, which progressed after 24 months. Gram-positive anaerobic bacteria and extraradicular biofilm seem to participate in the maintenance of persistent periapical pathology, and endodontic retreatment followed by periapical microsurgery proved to be a successful alternative in the

  1. Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, Kirsten Egebjerg; Schmiedel, Sven; Frederiksen, Kirsten

    2012-01-01

    were also conducted. Hazard ratios (HRs) for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CIs) were calculated in the 2 groups. RESULTS: Among high-risk HPV positive women......BACKGROUND: Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. METHODS: In a population-based cohort study, 8,656 women underwent a structured interview......, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n=1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection...

  2. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

  3. Persistent extra-axial post-surgical collections and Propionibacterium acnes infection. Presentation of two cases and literature review.

    Science.gov (United States)

    González, Pedro; Thenier, José; Galárraga, Raúl; de la Lama, Adolfo; Azevedo, Eva; Conde, Cesáreo

    It is common to observe the persistence of extra-axial collections after craniotomies. Most of these disappear in weeks or months but some remain. The onset of focal symptoms or the growth of these persistent collections months or years after surgery may indicate the presence of a chronic and latent infection by germs of low virulence such as Propionibacterium acnes (P. acnes). We present two clinical cases with persistent extra-axial collections, which required surgery years after diagnosis, in which P. acnes was isolated as an aetiological agent and we reviewed the literature published in this regard. These are two patients who, following surgical procedures (decompressive craniectomy for severe TBI and craniotomy for right parietal meningioma) and extra-axial collections were kept, which were monitored over time and then were infected and required emergency evacuation. In these collections P. acnes grew as a causal agent and required targeted antibiotics. We must consider P. acnes as an infectious agent of post-surgical collections of long evolution. Atypical presentation and radiological changes may be helpful in diagnosis. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012-2015: a retrospective cohort study

    NARCIS (Netherlands)

    Hananta, I. Putu Yuda; de Vries, Henry John Christiaan; van Dam, Alje P.; van Rooijen, Martijn Sebastiaan; Soebono, Hardyanto; Schim van der Loeff, Maarten Franciscus

    2017-01-01

    Infection of Neisseria gonorrhoeae in the pharynx (pharyngeal Ng) is associated with gonococcal transmission and development of antimicrobial resistance. We assessed proportion of and determinants for persistence after treatment of pharyngeal Ng. At the STI clinic of Amsterdam, the Netherlands,

  5. IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Høgh-Petersen, Mette; Storm, Pernille

    2014-01-01

    herpes virus infection, we infected IFNγ/perforin double deficient C57BL/6 mice and followed the outcome of infection. While absence of perforin prevented the splenic atrophy in IFNγ deficient mice, fibrosis did not disappear. Moreover, double deficient mice developed extreme splenomegaly, were unable...... in double deficient mice, other aspects are exaggerated, and the normal architecture of the spleen is completely destroyed. Thus, IFNγ and perforin work in concert to minimize pathology and control the viral load. In the absence of both effector molecules, the balancing race between the virus and the host...

  6. Persistence of Penaeus stylirostris densovirus delays mortality caused by white spot syndrome virus infection in black tiger shrimp (Penaeus monodon)

    Science.gov (United States)

    2013-01-01

    Background Persistent infection of Penaeus stylirostris densovirus (PstDNV) (also called IHHNV) and its non-infectious inserts in the black tiger shrimp, Penaeus monodon (P. monodon) genome are commonly found without apparent disease. Here, we introduced the method of multiplex PCR in order to differentiate shrimp with viral inserts from ones with the infectious virus. The method allowed us to study the effect of pre-infection of IHHNV, in comparison to IHHNV inserts, on WSSV resistance in P. monodon. Results A multiplex PCR system was developed to amplify the entire IHHNV genome, ensuring the accurate diagnosis. Field samples containing IHHNV DNA templates as low as 20 pg or equivalent 150 viral copies can be detected by this method. By challenging the two groups of diagnosed shrimp with WSSV, we found that shrimp with IHHNV infection and those with viral inserts responded to WSSV differently. Considering cumulative mortality, average time to death of shrimp in IHHNV-infected group (day 14) was significantly delayed relative to that (day 10) of IHHNV-inserted group. Real-time PCR analysis of WSSV copy number indicated the lower amount of WSSV in the IHHNV-infected group than the virus-inserted group. The ratio of IHHNV: WSSV copy number in all determined IHHNV-infected samples ranged from approximately 4 to 300-fold. Conclusion The multiplex PCR assay developed herein proved optimal for convenient differentiation of shrimp specimens with real IHHNV infection and those with insert types. Diagnosed shrimp were also found to exhibit different WSSV tolerance. After exposed to WSSV, the naturally pre-infected IHHNV P. monodon were less susceptible to WSSV and, consequently, survived longer than the IHHNV-inserted shrimp. PMID:23414329

  7. Naturally occurring mutations in large surface genes related to occult infection of hepatitis B virus genotype C.

    Directory of Open Access Journals (Sweden)

    Hong Kim

    Full Text Available Molecular mechanisms related to occult hepatitis B virus (HBV infection, particularly those based on genotype C infection, have rarely been determined thus far in the ongoing efforts to determine infection mechanisms. Therefore, we aim to elucidate the mutation patterns in the surface open reading frame (S ORF underlying occult infections of HBV genotype C in the present study. Nested PCRs were applied to 624 HBV surface antigen (HBsAg negative Korean subjects. Cloning and sequencing of the S ORF gene was applied to 41 occult cases and 40 control chronic carriers. Forty-one (6.6% of the 624 Korean adults with HBsAg-negative serostatus were found to be positive for DNA according to nested PCR tests. Mutation frequencies in the three regions labeled here as preS1, preS2, and S were significantly higher in the occult subjects compared to the carriers in all cases. A total of two types of deletions, preS1 deletions in the start codon and preS2 deletions as well as nine types of point mutations were significantly implicated in the occult infection cases. Mutations within the "a" determinant region in HBsAg were found more frequently in the occult subjects than in the carriers. Mutations leading to premature termination of S ORF were found in 16 occult subjects (39.0% but only in one subject from among the carriers (2.5%. In conclusion, our data suggest that preS deletions, the premature termination of S ORF, and "a" determinant mutations are associated with occult infections of HBV genotype C among a HBsAg-negative population. The novel mutation patterns related to occult infection introduced in the present study can help to broaden our understanding of HBV occult infections.

  8. Distribution, persistence and interchange of Epstein-Barr virus strains among PBMC, plasma and saliva of primary infection subjects.

    Science.gov (United States)

    Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

    2015-01-01

    Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle.

  9. Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation.

    Science.gov (United States)

    Misme-Aucouturier, Barbara; Albassier, Marjorie; Alvarez-Rueda, Nidia; Le Pape, Patrice

    2017-01-01

    A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at an in vitro cellular scale, Candida and human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32 Candida albicans and non-albicans (C. glabrata, C. tropicalis, C. parapsilosis, C. dubliniensis, C. lusitaniae, C. krusei, and C. kefyr) clinical isolates, we showed that Candida spp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to the Candida species. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response against Candida spp. Higher proportions of neutrophils and elevated CD4 + /CD8 + T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence of Candida could result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4 lo CD8 hi doubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence. Copyright © 2016 Misme-Aucouturier et al.

  10. Persistent Inflammation and Endothelial Activation in HIV-1 Infected Patients after 12 Years of Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L

    2013-01-01

    The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....

  11. Parity as a cofactor for high-grade cervical disease among women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, K E; Schmiedel, S; Norrild, B

    2013-01-01

    BACKGROUND:Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent...... human papillomavirus (HPV) infection.METHODS:A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (~13 years) on cervical lesions was obtained from...

  12. Factors associated with type-specific persistence of high-risk human papillomavirus infection

    DEFF Research Database (Denmark)

    Stensen, Signe; Kjær, Susanne K; Jensen, Signe Marie

    2016-01-01

    of pregnancies or births or use of a hormonal intrauterine device, hormonal therapy or nonsteroidal anti-inflammatory drugs was not associated with risk for HR HPV persistence. A history of genital warts and current use of oral contraceptives or systemic glucocorticoids increased the risk, potentially indicating...

  13. Smallpox: An eradicated infection with persistent sequels - Case report and a brief on smallpox

    International Nuclear Information System (INIS)

    Jastaneiah, Sabah

    2009-01-01

    Sequelae of smallpox infection on the ocular surface are still seen, including corneal scars adherent leukoma and phthisical globes. This paper will report another sequel of smallpox infection causing inadvertent bleb in a 62-year-old diabetic female with no history of ocular surgery or trauma in either eye. The patient had smallpox infection during her childhood. Her follow up extended from May 1997 until August 2007 with a constant eye examinations including controlled intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked pupil. (author)

  14. [The influence of Helicobacter pylori infection on the occurance of gastroesophageal reflux in patients with renal insufficiency].

    Science.gov (United States)

    Stolić, Radojica; Jovanović, Aleksandar; Perić, Vladan; Trajković, Goran; Zivić, Ziva; Stolić, Dragica; Lazarević, Tatjana; Sovtić, Sasa

    2007-12-01

    Gastric acid is a key factor in the pathophysiology of gastroesophageal reflux disease. A plausible mechanism by which the Helicobacter pylori infection might protect against reflux disease is by its propensity to produce atrophic gastritis. The aim of the study was to establish the influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with different stages of renal insufficiency. The examination was organized as a prospective, clinical study and involved 68 patients--33 patients with preterminal stage of renal failure and 35 patients with terminal renal insufficiency. Due to dyspeptic difficulties, in all the patients there was preformed upper esophagogastroscopy and Helicobacter pylori infection was found by ureasa test. The patients with preterminal renal insufficiency were significantly younger than patients with terminal renal failure (53.4 +/- 11.1 vs. 65.4 +/- 12.3 years; p = 0.014). There was found a statistically significant difference between the groups in Helicobacter pylori infection (p = 0.03), hiatal hernia (p = 0.008), gastroesophageal reflux disease (p = 0.007), and duodenal ulcer (p = 0.002). Using the multiple non-parametric correlative analysis there was confirmed a negative correlation between Helicobacter pylori infection and gastro-esophageal reflux disease (Kendal tauB = -0.523; p = 0.003) and hiatal hernia (Kendal tauB = 0.403; p = 0.021), while there was found a positive correlation between gastro-esophageal reflux disease and hiatal hernia (Kendal tauB = 0.350; p = 0.044). Helicobacter pylori infection is a significant protective parameter of the incidence of gastro-esophageal reflux disease in patients with both pre-terminal and terminal renal insufficiency.

  15. The role of sexual behavior and human papillomavirus persistence in predicting repeated infections with new human papillomavirus types.

    Science.gov (United States)

    Moscicki, Anna-Barbara; Ma, Yifei; Jonte, Janet; Miller-Benningfield, Susanna; Hanson, Evelyn; Jay, Julie; Godwin de Medina, Cheryl; Farhat, Sepideh; Clayton, Lisa; Shiboski, Stephen

    2010-08-01

    Although human papillomavirus (HPV) infections are common in young women, the rate of and risk for repeated new infections are not well documented. We examined the rate of and risks for new HPV detection in young women. We used data from an ongoing study of HPV, initiated in 1990. Sexually active women ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing were done at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with first HPV detection, time to the next (second) visit (event) with detection of new HPV types, and then the second event to time to third event was calculated. Risks were determined using Cox proportional hazard model. Sixty-nine percent of 1,125 women had a second event, and of those with a second event, 63% had a third event by 3 years, respectively. Women with HPV persistence from initial visit to second event [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10 (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for third event were similar. This study documents the repeated nature of HPV infections in young women and their association with sexual risk behaviors. This finding underscores the lack of clinical utility of HPV testing in young women. Further studies are needed to examine host factors that lead to HPV acquisition and persistence. (c)2010 AACR.

  16. Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection

    Science.gov (United States)

    Tran, Si C.; Pham, Tu M.; Nguyen, Lam N.; Park, Eun-Mee; Lim, Yun-Sook

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and ultimately hepatocellular carcinoma. However, the mechanisms underlying HCV-induced liver pathogenesis are still not fully understood. By transcriptome sequencing (RNA-Seq) analysis, we recently identified host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these, tribbles homolog 3 (TRIB3) was selected for further characterization. TRIB3 was initially identified as a binding partner of protein kinase B (also known as Akt). TRIB3 blocks the phosphorylation of Akt and induces apoptosis under endoplasmic reticulum (ER) stress conditions. HCV has been shown to enhance Akt phosphorylation for its own propagation. In the present study, we demonstrated that both mRNA and protein levels of TRIB3 were increased in the context of HCV replication. We further showed that promoter activity of TRIB3 was increased by HCV-induced ER stress. Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased HCV replication. By employing an HCV pseudoparticle entry assay, we further showed that TRIB3 was a negative host factor involved in HCV entry. Both in vitro binding and immunoprecipitation assays demonstrated that HCV NS3 specifically interacted with TRIB3. Consequently, the association of TRIB3 and Akt was disrupted by HCV NS3, and thus, TRIB3-Akt signaling was impaired in HCV-infected cells. Moreover, HCV modulated TRIB3 to promote extracellular signal-regulated kinase (ERK) phosphorylation, activator protein 1 (AP-1) activity, and cell migration. Collectively, these data indicate that HCV exploits the TRIB3-Akt signaling pathway to promote persistent viral infection and may contribute to HCV-mediated pathogenesis. IMPORTANCE TRIB3 is a pseudokinase protein that acts as an adaptor in signaling pathways for important cellular processes. So far, the functional involvement of

  17. Spatial Genetic Structure of Coffee-Associated Xylella fastidiosa Populations Indicates that Cross Infection Does Not Occur with Sympatric Citrus Orchards.

    Science.gov (United States)

    Francisco, Carolina S; Ceresini, Paulo C; Almeida, Rodrigo P P; Coletta-Filho, Helvécio D

    2017-04-01

    Xylella fastidiosa, an economically important plant-pathogenic bacterium, infects both coffee and citrus trees in Brazil. Although X. fastidiosa in citrus is well studied, knowledge about the population structure of this bacterium infecting coffee remains unknown. Here, we studied the population structure of X. fastidiosa infecting coffee trees in São Paulo State, Brazil, in four regions where citrus is also widely cultivated. Genotyping of over 500 isolates from coffee plants using 14 genomic microsatellite markers indicated that populations were largely geographically isolated, as previously found with populations of X. fastidiosa infecting citrus. These results were supported by a clustering analysis, which indicated three major genetic groups among the four sampled regions. Overall, approximately 38% of isolates showed significant membership coefficients not related to their original geographical populations (i.e., migrants), characterizing a significant degree of genotype flow among populations. To determine whether admixture occurred between isolates infecting citrus and coffee plants, one site with citrus and coffee orchards adjacent to each other was selected; over 100 isolates were typed from each host plant. No signal of natural admixture between citrus- and coffee-infecting isolates was found; artificial cross-infection assays with representative isolates also yielded no successful cross infection. A comparison determined that X. fastidiosa populations from coffee have higher genetic diversity and allelic richness compared with citrus. The results showed that coffee and citrus X. fastidiosa populations are effectively isolated from each other and, although coffee populations are spatially structured, migration has an important role in shaping diversity.

  18. HoBi-like virus challenge of pregnant cows that had previously given birth to calves persistently infected with bovine viral diarrhea virus

    Science.gov (United States)

    The ability of bovine viral diarrhea viruses (BVDV) to establish persistent infection (PI) following fetal infection is central to keeping these viruses circulating. Similarly, an emerging species of pestivirus, HoBi-like viruses, is also able to establish PIs. Dams that are not PI, but carrying PI ...

  19. Detection of foot-and-mouth disease virus RNA in pharyngeal epithelium biopsy samples obtained from infected cattle: Investigation of possible sites of virus replication and persistence

    DEFF Research Database (Denmark)

    Stenfeldt, Anna Carolina; Belsham, Graham

    2012-01-01

    measurements of the levels of FMDV RNA in the DSP as well as mandibular and retropharyngeal lymph nodes beyond 28 days after infection. Results indicated only low levels of FMDV RNA present in samples of pharyngeal epithelia during both early and persistent phases of infection with significantly higher levels...... of virus detected in pharyngeal excretions. It is concluded that the targeted area for sampling within the DSP does not harbour significant levels of virus replication during acute or persistent FMDV infection in cattle. Furthermore, the DSP and the mandibular and retropharyngeal lymph nodes cannot...

  20. [Assessment of the treatment with imiquimod in persistent infection by human papillomavirus with the polimerase chain reaction method].

    Science.gov (United States)

    Hernández Quijano, Tomás; Illanes Aguiar, Berenice; Salas Linares, Natividad; Alarcón Romero, Luz del Carmen; Hernández Valencia, Marcelino

    2006-06-01

    Molecular studies have shown that oncogenic genotypes of human papillomavirus (HPV) are the main risk factor for cervical cancer development. Sub-clinical wound does not cause symptoms and is diagnosed by colposcopy or histology, in addition the latent infection is associated with the presence of DNA of the HPV, but when clinical and histological abnormalities are not presented only molecular techniques can detect this infection. To determine if complementary processing with imiquimod, recent medicament with powerful antiviral activity in vitro as in vivo, reduces the cervical persistence of HPV. This study was carried out with 87 patients, who had antecedents of HPV cervical and intraepithelial wound with low degree. Patients were divided as follows: treated with cryotherapy, cervical loop electrosurgical and imiquimod, all with diagnosis by cervical cytology, colposcopy and polymerase chain reaction (PCR) for HPV. At 3, 6 and 12 months after the processing, PCR, cervical cytology and colposcopy control were carried out again. Out of the 87 patients studied, 11% (10) patients treated with cervical cytology were positive for VPH; with colposcopy 8% (7) of patients and with PCR 40% (34) of patients; decreased persistence with combined methods of loop and imiquimod was obtained in 29% (5) patients; however, when utilized imiquimod alone, there were 55% (11) patients with persistence determined by PCR method. Imiquimod appears to be beneficial in 45% of the patients, in contrast with efficacy reported until 85% in genitals and annals warts, in addition, the capacity of eliminating the viruses has been shown, therefore it is possible that its potential effect could be observed long-time. It is evident that the percentages of viral detection are improved for PCR method, compared with indirect methods as cervical cytology and colposcopy, which is favorable when virus serotypes are of high degree of transformation and ablative methods should be conservatives due to

  1. Bearded dragons (Pogona vitticeps) asymptomatically infected with Devriesea agamarum are a source of persistent clinical infection in captive colonies of dab lizards (Uromastyx sp.).

    Science.gov (United States)

    Devloo, R; Martel, A; Hellebuyck, T; Vranckx, K; Haesebrouck, F; Pasmans, F

    2011-06-02

    Devriesea agamarum causes dermatitis and septicaemia in a variety of lizards, notably those belonging to the genus Uromastyx, whereas other species such as bearded dragons (Pogona vitticeps) seem to be asymptomatic carriers. Using amplified fragment length polymorphism (AFLP), the relatedness between 69 D. agamarum isolates was examined. The isolates derived from 44 diseased lizards, of which 31 belonged to the genus Uromastyx, and from 25 healthy lizards, of which 21 were bearded dragons. Eight AFLP genotypes were obtained, four of which comprised 93% of the isolates. These four genotypes were each present in 2, 2, 8 and 13 different captive colonies. Up to three genotypes were isolated from a single infected colony simultaneously. On two occasions, the same genotype was found in healthy bearded dragons and diseased Uromastyx lizards from the same colony, confirming the role of the former as an asymptomatic source of infection for the latter. Two genotypes, comprising 12 isolates, were exclusively associated with diseased Uromastyx lizards, suggesting strain dependent host adaptation. Finally, D. agamarum was shown to be able to persist for at least seven years in a lizard colony, persistently causing severe disease in several lizard species. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Uropathogenic Escherichia coli metabolite-dependent quiescence and persistence may explain antibiotic tolerance during urinary tract infection

    DEFF Research Database (Denmark)

    Leatham-Jensen, Mary P.; Mokszycki, Matthew E.; Rowley, David C.

    2016-01-01

    infections by interfering with quiescence and persistence. IMPORTANCE Recurrent urinary tract infections (UTIs) affect 10 to 40% of women. In up to 77% of those cases, the recurrent infections are caused by the same uropathogenic E. coli (UPEC) strain that caused the initial infection. Upon infection...... of urothelial transitional cells in the bladder, UPEC appear to enter a nongrowing quiescent intracellular state that is thought to serve as a reservoir responsible for recurrent UTIs. Here, we report that many UPEC strains enter a quiescent state when ≤10(6) CFU are seeded on glucose M9 minimal medium agar...

  3. Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

    Science.gov (United States)

    Stieh, Daniel J; Maric, Danijela; Kelley, Z L; Anderson, Meegan R; Hattaway, Holly Z; Beilfuss, Beth A; Rothwangl, Katharina B; Veazey, Ronald S; Hope, Thomas J

    2014-10-01

    The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.

  4. Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James; Chang, J Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J; Van Der Weyden, Carrie; Prince, H Miles; Cameron, Paul U; Lewin, Sharon R

    2017-08-24

    To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells. Case report. Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells. Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

  5. Differentiated Approach to the Treatment and Secondary Prevention of Asthma on the Background of Persistent Infections in Children

    Directory of Open Access Journals (Sweden)

    O.Ye. Chernyshova

    2016-11-01

    Full Text Available Thе article describes a differentiated approach to the treatment and secondary prevention of asthma occurring on the background of intracellular infections caused by the herpes simplex virus types I and II, cytomegalovirus, Epstein-Barr virus in children. The results confirmed the need for addition to the basic therapy of asthma the etiopathogenetic treatment, in particular, administration of acyclic nucleosides or macrolides depending on diagnosed infection, immunomodulators and alpha-2b-interferon (Laferobion to decrease the severity of disease and to reduce disability.

  6. The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection

    DEFF Research Database (Denmark)

    Del Bel Belluz, Lisa; Guidi, Riccardo; Pateras, Ioannis S.

    2016-01-01

    Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this i...

  7. Identification and Pathological Characterization of Persistent Asymptomatic Ebola Virus infection in Rhesus Monkeys

    Science.gov (United States)

    2017-05-12

    2454 (2015). 412 16. Blackley, D.J., et al. Reduced evolutionary rate in reemerged Ebola virus 413 transmission chains. Sci Adv 2, e1600378 (2016). 414...and Marburgvirus Infections. in Harrison’s Principles of 456 Internal Medicine , Vol. 2 (eds. Kasper, D.L., et al.) 1323-1329 (McGraw-Hill 457

  8. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE.

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    Dongseob Tark

    Full Text Available Bovine spongiform encephalopathy (BSE is a zoonotic transmissible spongiform encephalopathy (TSE thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD. Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

  9. Dynamics of Persistent and Acute Deformed Wing Virus Infections in Honey Bees, Apis mellifera

    Directory of Open Access Journals (Sweden)

    Jay D. Evans

    2011-12-01

    Full Text Available The dynamics of viruses are critical to our understanding of disease pathogenesis. Using honey bee Deformed wing virus (DWV as a model, we conducted field and laboratory studies to investigate the roles of abiotic and biotic stress factors as well as host health conditions in dynamics of virus replication in honey bees. The results showed that temperature decline could lead to not only significant decrease in the rate for pupae to emerge as adult bees, but also an increased severity of the virus infection in emerged bees, partly explaining the high levels of winter losses of managed honey bees, Apis mellifera, around the world. By experimentally exposing adult bees with variable levels of parasitic mite Varroa destructor, we showed that the severity of DWV infection was positively correlated with the density and time period of Varroa mite infestation, confirming the role of Varroa mites in virus transmission and activation in honey bees. Further, we showed that host conditions have a significant impact on the outcome of DWV infection as bees that originate from strong colonies resist DWV infection and replication significantly better than bee originating from weak colonies. The information obtained from this study has important implications for enhancing our understanding of host‑pathogen interactions and can be used to develop effective disease control strategies for honey bees.

  10. New bacterial composition in primary and persistent/secondary endodontic infections with respect to clinical and radiographic findings.

    Science.gov (United States)

    Tennert, Christian; Fuhrmann, Maximilian; Wittmer, Annette; Karygianni, Lamprini; Altenburger, Markus J; Pelz, Klaus; Hellwig, Elmar; Al-Ahmad, Ali

    2014-05-01

    The aim of the present study was to analyze the microbiota of primary and secondary/persistent endodontic infections of patients undergoing endodontic treatment with respect to clinical and radiographic findings. Samples from the root canals of 21 German patients were taken using 3 sequential sterile paper points. In the case of a root canal filling, gutta-percha was removed with sterile files, and samples were taken using sterile paper points. The samples were plated, and microorganisms were then isolated and identified morphologically by biochemical analysis and sequencing the 16S rRNA genes of isolated microorganisms. In 12 of 21 root canals, 33 different species could be isolated. Six (50%) of the cases with isolated microorganisms were primary, and 6 (50%) cases were endodontic infections associated with root-filled teeth. Twelve of the isolated species were facultative anaerobic and 21 obligate anaerobic. Monomicrobial infections were found for Enterococcus faecalis and Actinomyces viscosus. E. faecalis was most frequently isolated in secondary endodontic infections (33%). Moraxella osloensis was isolated from a secondary endodontic infection that had an insufficient root canal filling accompanied by a mild sensation of pain. A new bacterial composition compromising Atopobium rimae, Anaerococcus prevotii, Pseudoramibacter alactolyticus, Dialister invisus, and Fusobacterium nucleatum was recovered from teeth with chronic apical abscesses. New bacterial combinations were found and correlated to clinical and radiographic findings, particularly to chronic apical abscesses. M. osloensis was detected in root canals for the second time and only in German patients. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

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    Genevieve E Martin

    Full Text Available Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001, soluble CD163 (sCD163, p = 0.001, sCD14 (p = 0.022, neopterin (p = 0.029 and an increased proportion of CD16(+ monocytes (p = 0.009 compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002 suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+ T lymphocytes.Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  12. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Science.gov (United States)

    Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

    2013-01-01

    Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  13. Evolution of a Cell Culture-Derived Genotype 1a Hepatitis C Virus (H77S.2) during Persistent Infection with Chronic Hepatitis in a Chimpanzee

    Science.gov (United States)

    Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M.; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E.

    2014-01-01

    ABSTRACT Persistent infection is a key feature of hepatitis C virus (HCV). However, chimpanzee infections with cell culture-derived viruses (JFH1 or related chimeric viruses that replicate efficiently in cell culture) have been limited to acute-transient infections with no pathogenicity. Here, we report persistent infection with chronic hepatitis in a chimpanzee challenged with cell culture-derived genotype 1a virus (H77S.2) containing 6 cell culture-adaptive mutations. Following acute-transient infection with a chimeric H77/JFH1 virus (HJ3-5), intravenous (i.v.) challenge with 106 FFU H77S.2 virus resulted in immediate seroconversion and, following an unusual 4- to 6-week delay, persistent viremia accompanied by alanine aminotransferase (ALT) elevation, intrahepatic innate immune responses, and diffuse hepatopathy. This first persistent infection with cell culture-produced HCV provided a unique opportunity to assess evolution of cell culture-adapted virus in vivo. Synonymous and nonsynonymous nucleotide substitution rates were greatest during the first 8 weeks of infection. Of 6 cell culture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replaced by T2204 within 8 weeks of infection. By 62 weeks, 4 of 6 mutations had reverted to the wild-type sequence, and all reverted to the wild-type sequence by 194 weeks. The data suggest H77S.2 virus has greater potential for persistence and pathogenicity than JFH1 and demonstrate both the capacity of a nonfit virus to persist for weeks in the liver in the absence of detectable viremia as well as strong selective pressure against cell culture-adaptive mutations in vivo. IMPORTANCE This study shows that mutations promoting the production of infectious genotype 1a HCV in cell culture have the opposite effect and attenuate replication in the liver of the only fully permissive animal species other than humans. It provides the only example to date of persistent infection in a chimpanzee

  14. Evolution of a cell culture-derived genotype 1a hepatitis C virus (H77S.2) during persistent infection with chronic hepatitis in a chimpanzee.

    Science.gov (United States)

    Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E; Lemon, Stanley M

    2014-04-01

    Persistent infection is a key feature of hepatitis C virus (HCV). However, chimpanzee infections with cell culture-derived viruses (JFH1 or related chimeric viruses that replicate efficiently in cell culture) have been limited to acute-transient infections with no pathogenicity. Here, we report persistent infection with chronic hepatitis in a chimpanzee challenged with cell culture-derived genotype 1a virus (H77S.2) containing 6 cell culture-adaptive mutations. Following acute-transient infection with a chimeric H77/JFH1 virus (HJ3-5), intravenous (i.v.) challenge with 10(6) FFU H77S.2 virus resulted in immediate seroconversion and, following an unusual 4- to 6-week delay, persistent viremia accompanied by alanine aminotransferase (ALT) elevation, intrahepatic innate immune responses, and diffuse hepatopathy. This first persistent infection with cell culture-produced HCV provided a unique opportunity to assess evolution of cell culture-adapted virus in vivo. Synonymous and nonsynonymous nucleotide substitution rates were greatest during the first 8 weeks of infection. Of 6 cell culture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replaced by T2204 within 8 weeks of infection. By 62 weeks, 4 of 6 mutations had reverted to the wild-type sequence, and all reverted to the wild-type sequence by 194 weeks. The data suggest H77S.2 virus has greater potential for persistence and pathogenicity than JFH1 and demonstrate both the capacity of a nonfit virus to persist for weeks in the liver in the absence of detectable viremia as well as strong selective pressure against cell culture-adaptive mutations in vivo. This study shows that mutations promoting the production of infectious genotype 1a HCV in cell culture have the opposite effect and attenuate replication in the liver of the only fully permissive animal species other than humans. It provides the only example to date of persistent infection in a chimpanzee challenged with cell

  15. Persistence of subclinical deformed wing virus infections in honeybees following Varroa mite removal and a bee population turnover.

    Directory of Open Access Journals (Sweden)

    Barbara Locke

    Full Text Available Deformed wing virus (DWV is a lethal virus of honeybees (Apis mellifera implicated in elevated colony mortality rates worldwide and facilitated through vector transmission by the ectoparasitic mite Varroa destructor. Clinical, symptomatic DWV infections are almost exclusively associated with high virus titres during pupal development, usually acquired through feeding by Varroa mites when reproducing on bee pupae. Control of the mite population, generally through acaricide treatment, is essential for breaking the DWV epidemic and minimizing colony losses. In this study, we evaluated the effectiveness of remedial mite control on clearing DWV from a colony. DWV titres in adult bees and pupae were monitored at 2 week intervals through summer and autumn in acaricide-treated and untreated colonies. The DWV titres in Apistan treated colonies was reduced 1000-fold relative to untreated colonies, which coincided with both the removal of mites and also a turnover of the bee population in the colony. This adult bee population turnover is probably more critical than previously realized for effective clearing of DWV infections. After this initial reduction, subclinical DWV titres persisted and even increased again gradually during autumn, demonstrating that alternative non-Varroa transmission routes can maintain the DWV titres at significant subclinical levels even after mite removal. The implications of these results for practical recommendations to mitigate deleterious subclinical DWV infections and improving honeybee health management are discussed.

  16. Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co-infection.

    Science.gov (United States)

    Cao, Ying; Zhang, Yu; Bao, Yi; Zhang, Renwen; Zhang, Xiaxia; Xia, Wei; Wu, Hao; Xu, Xiaoyuan

    2016-05-01

    The aim of this study was to measure the frequency of natural mutations in hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected protease inhibitor (PI)-naive patients. Population sequence of the non-structural (NS)3 protease gene was evaluated in 90 HCV mono-infected and 96 HIV/HCV co-infected PI treatment-naive patients. The natural prevalence of PI resistance mutations in both groups was compared. Complete HCV genotype 1b NS3 sequence information was obtained for 152 (81.72%) samples. Seven sequences (8.33%) of the 84 HCV mono-infected patients and 21 sequences (30.88%) of the 68 HIV/HCV co-infected patients showed amino acid substitutions associated with HCV PI resistance. There was a significant difference in the natural prevalence of PI resistance mutations between these two groups (P = 0.000). The mutations T54S, R117H and N174F were observed in 1.19%, 5.95% and 1.19% of HCV mono-infected patients. The mutations F43S, T54S, Q80K/R, R155K, A156G/V, D168A/E/G and V170A were found in 1.47%, 4.41%, 1.47%/1.47%, 2.94%, 23.53%/1.47%, 1.47%/1.47%/1.47% and 1.47% of HIV/HCV co-infected patients, respectively. In addition, the combination mutations in the NS3 region were detected only in HIV/HCV genotype 1b co-infected patients. Naturally occurring HCV PI resistance mutations existed in HCV mono-infected and HIV/HCV co-infected genotype 1b PI-naive patients. HIV co-infection was associated with a greater frequency of PI resistance mutations. The impact of HIV infection on baseline HCV PI resistance mutations and treatment outcome in chronic hepatitis C (CHC) patients should be further analyzed. © 2015 The Japan Society of Hepatology.

  17. Reactivation of hepatitis B virus infection with persistently negative HBsAg on three HBsAg assays in a lymphoma patient undergoing chemotherapy.

    Science.gov (United States)

    Cheung, Wing-I; Chan, Henry Lik-Yuen; Leung, Vincent King-Sun; Tse, Chi-Hang; Fung, Kitty; Lin, Shek-Ying; Wong, Ann; Wong, Vincent Wai-Sun; Chau, Tai-Nin

    2010-02-01

    In patients with occult hepatitis B virus (HBV) infection, acute exacerbation may occur when they become immunocompromised. Usually, these patients develop hepatitis B surface antigen (HBsAg) seroreversion during the flare. Here we report on a patient with occult HBV infection, who developed HBV exacerbation after chemotherapy for diffuse large B-cell lymphoma. The resurgence of HBV DNA preceded the elevation of liver enzymes for 20 weeks. Atypically, despite high viraemia, serological tests showed persistently negative HBsAg using three different sensitive HBsAg assays (i.e., Architect, Murex and AxSYM). On comparing the amino acid sequence of the index patient with the consensus sequence, five mutations were found at pre-S1, five at pre-S2 and twenty-three mutations at the S region. Six amino acid mutations were located in the 'a' determinant, including P120T, K122R, M133T, F134L, D144A and G145A. The mutants K122R, F134L and G145A in our patient have not been tested for their sensitivity to Architect and Murex assays by the previous investigators and might represent the escape mutants to these assays.

  18. Persistent infection by Staphylococcus epidermidis in endodontic flare-up: a case report.

    Science.gov (United States)

    Gonçalves, Simone Helena Ferreira; de Vasconcelos, Rafaela Andrade; Cavalcanti, Bruno das Neves; Camargo, Carlos Henrique Ribeiro

    2016-01-01

    Endodontic flare-ups are challenging situations and may result from selective growth of specific bacterial species; microbial cultures and antibiograms should be used to allow faster, successful management of refractory lesions. A 47-year-old man reported pain on percussion after uncomplicated retreatment of the maxillary left canine for prosthetic purposes. In the following days, pain dramatically increased, leading to removal of the filling and use of intracanal medication. After many unsuccessful attempts to resolve the problem, a microbial culture of the root canal detected the presence of Staphylococcus epidermidis. An antibiogram determined the best drug combination to control this infection: tetracycline (oxytetracycline hydrochloride, 500 mg orally) plus third-generation cephalosporin (ceftriaxone, 1 g intramuscularly). Once the infection was controlled, the root canal was obturated. There was a reduction in the area of radiolucency, and the patient reported no pain at a 2-year follow-up.

  19. Helicobacter pylori SabA Adhesin in Persistent Infection and Chronic Inflammation

    OpenAIRE

    Mahdavi, Jafar; Sondén, Berit; Hurtig, Marina; Olfat, Farzad O.; Forsberg, Lina; Roche, Niamh; Ångström, Jonas; Larsson, Thomas; Teneberg, Susann; Karlsson, Karl-Anders; Altraja, Siiri; Wadström, Torkel; Kersulyte, Dangeruta; Berg, Douglas E.; Dubois, Andre

    2002-01-01

    Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) wa...

  20. Biofilms and Persistent Wound Infections in United States Military Trauma Patients: a Case-control Analysis

    Science.gov (United States)

    2014-04-08

    Infect Dis. 2014, 21:21-23. 51. Hochbaum AI, Kolodkin-Gal I, Foulston L, Kolter R, Aizenberg J, Losick R: Inhibitory effects of D-amino acids on...Staphylococcus aureus biofilm development. J Bacteriol 2011, 193(20):5616–5622. 52. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R: D-amino...acids trigger biofilm dissambly. Science 2010, 328(5978):627–629. 53. Kolodkin-Gal I, Cao S, Chai L, Bottcher T, Kolter R, Clardy J, Losick R: A self

  1. [Co-occurence of indol-producing bacterial strains in the vagina of women infected with Chlamydia trachomatis].

    Science.gov (United States)

    Romanik, Małgorzata; Martirosian, Gayane; Wojciechowska-Wieja, Anna; Cieślik, Katarzyna; Kaźmierczak, Wojciech

    2007-08-01

    The aim of this study was to determine if cervicitis, caused by Chlamydia trachomatis (C. trachomatis), has an influence on the frequency of occurrence of selected aerobic and anaerobic bacterial strains, connected with etiology of aerobic vaginitis (AV) and bacterial vaginosis (BV). Indole-producing bacteria have received particular attention due to their possibly inductive role in chronic cervicitis caused by C. trachomatis. The swabs from vagina and cervical canal have been obtained from 122 women (aged 18-40). The presence of C. trachomatis antigen had been detected and diagnosed with the help of direct immunofluorescence, BV with Amesl and Nugent criteria, whereas the AV with Donders criteria. The identification of the bacterial strains isolated from vagina has been performed according to classical microbiological diagnostics. Disruption of vaginal microflora (4-10 in Nugent score) was determined in 11,5% of observed women. AV was diagnosed in 4.5% women with chlamydial cervicitis, BV was diagnosed in 10.9% and 5.45% of these women, on the basis of Amsel and Nugent criteria respectively. Indole-producing bacterial strains connected with BV and AV (Peptostreptococcus anaerobius, Propionibacterium acnes, Escherichia coli) have been isolated significantly more often from vagina of women infected with C trachomatis (p = 0.0405, chi2 = 4.20) and these findings confirm co-importance of indole-producing bacterial strains in cervicitis caused by C trachomatis .

  2. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Science.gov (United States)

    Maru, Saumya; Jin, Ge; Schell, Todd D; Lukacher, Aron E

    2017-04-01

    Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  3. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Directory of Open Access Journals (Sweden)

    Saumya Maru

    2017-04-01

    Full Text Available Establishing functional tissue-resident memory (TRM cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  4. Early postoperative endophthalmitis after pars plana Ahmed valve placement with persistent extraocular infection.

    Science.gov (United States)

    Park, Susanna S; Rabowsky, Jeffrey

    2007-01-01

    This article presents a case of early postoperative endophthalmitis that occurred after vitrectomy and Ahmed Glaucoma Valve (New World Medical, Inc., Rancho Cucamonga, CA) placement and was treated with intravitreal antibiotics. Intravenous vancomycin was started after aqueous culture grew methicillin-resistant Staphylococcus aureus. The endophthalmitis improved, but new purulent discharge around the peritomy was noted 10 days after presentation, requiring removal of the valve.

  5. Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Juan M Pacheco

    Full Text Available Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95% and dorsal soft palate (71.43%. FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within few epithelial cells in regions of mucosa-associated lymphoid tissue (MALT. Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE was identified for IP-10 (RE = 0.198, IFN-β (RE = 0.269, IL-12 (RE = 0.275, and IL-2 (RE = 0.312. Increased relative expression was detected for IL-6 (RE = 2.065. Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased levels of mRNA for several immunoregulatory cytokines in the infected tissues.

  6. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

    Directory of Open Access Journals (Sweden)

    Taisheng Li

    2006-12-01

    Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

  7. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART during acute HIV-1 infection: An observational study.

    Directory of Open Access Journals (Sweden)

    Timothy J Henrich

    2017-11-01

    Full Text Available It is unknown if extremely early initiation of antiretroviral therapy (ART may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male and 12 days (Participant B; 31-year-old male after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI following 32 weeks of continuous ART.Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF, plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA. Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse, but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input

  8. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    Full Text Available Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV and foot-and-mouth disease virus (FMDV mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP. PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of

  9. Persistent Cryptococcal Brain Infection despite Prolonged Immunorecovery in an HIV-Positive Patient

    Directory of Open Access Journals (Sweden)

    Tom Wingfield

    2014-01-01

    Full Text Available Background. HIV-positive people starting combined antiretroviral therapy may develop immune reconstitution to latent or treated opportunistic infections. Immune reconstitution to cerebral Cryptococcus is poorly understood and can be fatal. Case Presentation. A 33-year-old Zimbabwean female presented with cryptococcal meningitis and newly diagnosed HIV with a CD4 count of 51 cells/μL (4%. She was treated with amphotericin and flucytosine. Combined antiretroviral therapy was started four weeks later and she showed early improvement. However, over the ensuing 18 months, her clinical course was marked by periodic worsening with symptoms resembling cryptococcal meningitis despite having achieved CD4 counts ≥400 cells/μL. Although initially treated for relapsing cryptococcal immune reconstitution syndrome, a brain biopsy taken 17 months after initial presentation showed budding Cryptococci. Conclusion. This unusually protracted case highlights the difficulties in differentiating relapsing cryptococcal meningitis from immune reconstitution and raises questions concerning the optimum timing of initiation of combined antiretroviral therapy in such patients.

  10. Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure.

    Science.gov (United States)

    Yoo, Joseph; Hann, Hie-Won; Coben, Robert; Conn, Mitchell; DiMarino, Anthony J

    2018-04-20

    Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4⁻5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages.

  11. Persistence of highly pathogenic avian influenza virus (H7N1) in infected chickens: feather as a suitable sample for diagnosis.

    Science.gov (United States)

    Busquets, Núria; Abad, F Xavier; Alba, Anna; Dolz, Roser; Allepuz, Alberto; Rivas, Raquel; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

    2010-09-01

    Selection of an ideal sample is a vital element in early detection of influenza infection. Rapid identification of infectious individuals or animals is crucial not only for avian influenza virus (AIV) surveillance programmes, but also for treatment and containment strategies. This study used a combination of quantitative real-time RT-PCR with an internal positive control and a cell-titration system to examine the presence of virus in different samples during active experimental AIV infection and its persistence in the infected carcasses. Oropharyngeal/cloacal swabs as well as feather pulp and blood samples were collected from 15-day-old chicks infected with H7N1 highly pathogenic AIV (HPAIV) and the kinetics of virus shedding during active infection were evaluated. Additionally, several samples (muscle, skin, brain, feather pulp and oropharyngeal and cloacal swabs) were examined to assess the persistence of virus in the HPAIV-infected carcasses. Based on the results, feather pulp was found to be the best sample to detect and isolate HPAIV from infected chicks from 24 h after inoculation onwards. Kinetic studies on the persistence of virus in infected carcasses revealed that tissues such as muscle could potentially transmit infectious virus for 3 days post-mortem (p.m.), whilst other tissues such as skin, feather pulp and brain retained their infectivity for as long as 5-6 days p.m. at environmental temperature (22-23 degrees C). These results strongly favour feather as a useful sample for HPAIV diagnosis in infected chickens as well as in carcasses.

  12. Misadventure in Muirhouse. HIV infection: a modern plague and persisting public health problem.

    Science.gov (United States)

    Robertson, R

    2017-03-01

    This story is of particular interest and importance to Edinburgh and Scottish medicine. It describes the events in one general medical practice in Edinburgh, the Muirhouse Medical Group, and their impact and relationship to the AIDS pandemic. For many, the origin of HIV in the UK is now history. Since the introduction of HIV/AIDS into the intravenous illegal drug using community, much has changed but problems remain that should concern policy makers and clinicians. Reflections on the recent history of the HIV epidemic among drug users in the UK provide important insights into risks for current policy making and the potentially problematic direction that policy has taken. Rather than starting from a pragmatic baseline of harm minimisation, with its low cost, high impact, prevention approach, the emphasis, and consequently the resources, has been on a model of recovery which fails to acknowledge the fragile control maintained by early intervention and supporting treatments. In 2015, the re-emergence of HIV in a vulnerable inner city population of people who inject drugs highlighted a policy failure. An ongoing epidemic could and should have been prevented, as should several other recent epidemics of other viral or bacterial infections in urban populations in Scotland. The story of HIV is full of controversy, denial, prejudice and stigma. At all levels across the world from national presidents, governments and public opinion, progress has been impeded by these problems. People using drugs have an additional set of problems: criminality, poverty and marginalisation from education and the supports of main stream society. These continue to hamper efforts to improve lives and prevent disease.

  13. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  14. Epidemic myalgia and myositis associated with human parechovirus type 3 infections occur not only in adults but also in children: findings in Yamagata, Japan, 2014.

    Science.gov (United States)

    Mizuta, K; Yamakawa, T; Kurokawa, K; Chikaoka, S; Shimizu, Y; Itagaki, T; Katsushima, F; Katsushima, Y; Ito, S; Aoki, Y; Matoba, Y; Tanaka, S; Yahagi, K

    2016-04-01

    We previously reported an association between human parechovirus type 3 (HPeV3) and epidemic myalgia with myositis in adults during summers in which an HPeV3 outbreak occurred in children. However, this disease association has not yet been reported elsewhere. We have since continued our surveillance to accumulate data on this disease association and to confirm whether myalgia occurs in children as well as adults. Between June and August 2014, we collected 380 specimens from children with infectious diseases. We also collected clinical specimens from two adult and three paediatric patients suspected of myalgia. We then performed virus isolation and reverse-transcription-PCR using the collected specimens. We detected HPeV3 in 26 children with infectious diseases, which we regarded as indicating an outbreak. We also confirmed HPeV3 infection in all patients suspected of myalgia. In particular the symptoms in two boys, complaining of myalgia and fever, closely matched the criteria for adult myalgia. Based on our findings from 2008, 2011 and 2014, we again urge that clinical consideration be given to the relationship between myalgia and HPeV3 infections during HPeV3 outbreaks in children. Furthermore, our observations from 2014 suggest that epidemic myalgia and myositis occur not only in adults but also in children.

  15. Changes in IgA protease expression are conferred by changes in genomes during persistent infection by nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Gallo, Mary C; Kirkham, Charmaine; Eng, Samantha; Bebawee, Remon S; Kong, Yong; Pettigrew, Melinda M; Tettelin, Hervé; Murphy, Timothy F

    2018-05-14

    Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of chronic obstructive pulmonary disease (COPD). NTHi causes acute exacerbations of COPD and also causes persistent infection of the lower airways. NTHi expresses four IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates IgA protease expression during infection in COPD. To assess expression of IgA protease during natural infection in COPD, we studied IgA protease expression of 101 persistent strains (median duration of persistence 161 days, range 2 to 1422) collected longitudinally from patients enrolled in a 20-year study of COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in iga gene sequences result in changes in expression of IgA proteases by NTHi during persistent infection in the respiratory tract of patients with COPD. Copyright © 2018 American Society for Microbiology.

  16. Persistent environmental contamination with USA300 methicillin-resistant Staphylococcus aureus and other pathogenic strain types in households with S. aureus skin infections.

    Science.gov (United States)

    Eells, Samantha J; David, Michael Z; Taylor, Alexis; Ortiz, Nancy; Kumar, Neha; Sieth, Julia; Boyle-Vavra, Susan; Daum, Robert S; Miller, Loren G

    2014-11-01

    To understand the genotypic spectrum of environmental contamination of Staphylococcus aureus in households and its persistence. Prospective longitudinal cohort investigation. Index participants identified at 2 academic medical centers. Adults and children with S. aureus skin infections and their household contacts in Los Angeles and Chicago. Household fomites were surveyed for contamination at baseline and 3 months. All isolates underwent genetic typing. We enrolled 346 households, 88% of which completed the 3-month follow-up visit. S. aureus environmental contamination was 49% at baseline and 51% at 3 months. Among households with a USA300 methicillin-resistant S. aureus (MRSA) body infection isolate, environmental contamination with an indistinguishable MRSA strain was 58% at baseline and 63% at 3 months. Baseline factors associated with environmental contamination by the index subject's infection isolate were body colonization by any household member with the index subject's infection isolate at baseline (odds ratio [OR], 10.93 [95% confidence interval (CI), 5.75-20.79]), higher housing density (OR, 1.47 [95% CI, 1.10-1.96]), and more frequent household fomite cleaning (OR, 1.62 [95% CI, 1.16-2.27]). Household environmental contamination with the index subject's infection strain at 3 months was associated with USA300 MRSA and a synergistic interaction between baseline environmental contamination and body colonization by any household member with the index subject's infection strain. We found that infecting S. aureus isolates frequently persisted environmentally in households 3 months after skin infection. Presence of pathogenic S. aureus strain type in the environment in a household may represent a persistent reservoir that places household members at risk of future infection.

  17. Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells.

    Science.gov (United States)

    Xia, Lu; Dai, Lei; Yu, Qinghua; Yang, Qian

    2017-11-01

    Transmissible gastroenteritis virus (TGEV) is a coronavirus characterized by diarrhea and high morbidity rates, and the mortality rate is 100% in piglets less than 2 weeks old. Pigs infected with TGEV often suffer secondary infection by other pathogens, which aggravates the severity of diarrhea, but the mechanisms remain unknown. Here, we hypothesized that persistent TGEV infection stimulates the epithelial-mesenchymal transition (EMT), and thus enterotoxigenic Escherichia coli (ETEC) can more easily adhere to generating cells. Intestinal epithelial cells are the primary targets of TGEV and ETEC infections. We found that TGEV can persistently infect porcine intestinal columnar epithelial cells (IPEC-J2) and cause EMT, consistent with multiple changes in key cell characteristics. Infected cells display fibroblast-like shapes; exhibit increases in levels of mesenchymal markers with a corresponding loss of epithelial markers; have enhanced expression levels of interleukin-1β (IL-1β), IL-6, IL-8, transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α) mRNAs; and demonstrate increases in migratory and invasive behaviors. Additional experiments showed that the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways via TGF-β is critical for the TGEV-mediated EMT process. Cellular uptake is also modified in cells that have undergone EMT. TGEV-infected cells have higher levels of integrin α5 and fibronectin and exhibit enhanced ETEC K88 adhesion. Reversal of EMT reduces ETEC K88 adhesion and inhibits the expression of integrin α5 and fibronectin. Overall, these results suggest that TGEV infection induces EMT in IPEC-J2 cells, increasing the adhesion of ETEC K88 in the intestine and facilitating dual infection. IMPORTANCE Transmissible gastroenteritis virus (TGEV) causes pig diarrhea and is often followed by secondary infection by other pathogens. In this study, we showed

  18. Drought occurence

    Science.gov (United States)

    John W. Coulston

    2007-01-01

    Why Is Drought Important? Drought is an important forest disturbance that occurs regularly in the Western United States and irregularly in the Eastern United States (Dale and others 2001). Moderate drought stress tends to slow plant growth while severedrought stress can also reduce photosynthesis (Kareiva and others 1993). Drought can also interact with...

  19. Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

    Science.gov (United States)

    Hillemanns, Peter; Einstein, Mark H; Iversen, Ole Erik

    2015-02-01

    Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

  20. Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection.

    Science.gov (United States)

    Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

    2015-11-01

    The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by a segmented double-stranded RNA (dsRNA) genome. Further, we show that Dicer-2 predominantly targets viral dsRNA and produces 20-nucleotide (nt) vsRNAs, whereas an additional pathway is responsive to viral mRNA derived from segment 10. Importantly, vsRNA distributions, which define specific hot and cold spot profiles for each viral segment, to a considerable degree overlap between Dicer-2-related (19 to 21 nt) and Dicer-2-unrelated vsRNAs, suggesting a common origin for these profiles. We found a degenerate motif significantly enriched at the cut sites of vsRNAs of various lengths which link an unknown RNase to the origins of vsRNAs biogenesis and distribution. Accordingly, the indicated RNase activity may be an important early factor for the host's antiviral defense in Lepidoptera. This work contributes to the elucidation of the lepidopteran antiviral response against infection of segmented double-stranded RNA (dsRNA) virus (CPV; Reoviridae) and highlights the importance of viral small-RNA (vsRNA) analysis for getting insights into host-pathogen interactions. Three vsRNA pathways are implicated in antiviral defense. For dsRNA, two pathways are proposed, either based on Dicer-2 cleavage to generate 20-nucleotide vsRNAs or based on the activity of an uncharacterized endo-RNase that cleaves the viral RNA substrate at a degenerate motif. The analysis also indicates the existence of a degradation pathway that targets the positive strand of segment 10. Copyright © 2015, American

  1. Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis-associated skin ulcers on the face and surrounding a tracheotomy stoma.

    Science.gov (United States)

    Nagamoto, Eiko; Fujisawa, Akihiko; Yoshino, Yuichiro; Yoshitsugu, Kanako; Odo, Masashi; Watanabe, Hidetaka; Igata, Toshikatsu; Noguchi, Hiromitsu

    2014-01-01

    A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

  2. Rhinovirus infection results in stronger and more persistent genomic dysregulation: Evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence.

    Directory of Open Access Journals (Sweden)

    Peter W Heymann

    Full Text Available Rhinovirus (HRV is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined.Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis.At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation. At 36 hours (before the emergence of peak symptoms, 1329 genes were significantly altered from baseline in the asthmatics compared to 62 genes in the controls. At this time point, asthmatics lacked an increase in IL-10 signaling observed in the controls. At 7 days following HRV inoculation, 222 genes were significantly dysregulated in the asthmatics, whereas only 4 genes were dysregulated among controls. At this time point, the controls but not asthmatics demonstrated upregulation of SPINK5.As judged by the magnitude and persistence of dysregulated genes, asthmatics have a substantially different host response to HRV-A16 infection compared with non-asthmatic controls. Gene expression differences illuminate biologically plausible mechanisms that contribute to a better understanding of the pathogenesis of HRV-induced asthma exacerbations.

  3. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

    Science.gov (United States)

    Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

  4. Early discontinuation of antibiotic prophylaxis in patients with persistent primary vesicoureteral reflux initially detected during infancy: outcome analysis and risk factors for febrile urinary tract infection.

    Science.gov (United States)

    Moriya, Kimihiko; Mitsui, Takahiko; Kitta, Takeya; Nakamura, Michiko; Kanno, Yukiko; Kon, Masafumi; Nishimura, Yoko; Shinohara, Nobuo; Nonomura, Katsuya

    2015-02-01

    We retrospectively assessed the incidence of and risk factors for febrile urinary tract infection in children during active surveillance after early discontinuation of antibiotic prophylaxis. We retrospectively evaluated 9 females and 61 uncircumcised males diagnosed with primary vesicoureteral reflux before age 1 year who had persistent reflux on followup voiding cystourethrogram and were subsequently followed under active surveillance without continuous antibiotic prophylaxis. Patients with secondary vesicoureteral reflux or associated urological abnormality were excluded. Clinical outcomes, including incidence of febrile urinary tract infection and new scar formation, were evaluated. Risk factors for febrile urinary tract infection were also analyzed. Mean age at stopping continuous antibiotic prophylaxis was 21 months, and mean followup was 61 months. During active surveillance 21 patients had febrile urinary tract infection, and the 5-year infection-free rate under active surveillance was 67.5%. One or 2 foci of minimal new scarring developed in 4 of 16 patients who underwent followup dimercapto-succinic acid scan after febrile urinary tract infection. On multivariate analysis dilated vesicoureteral reflux on followup voiding cystourethrogram was the only significant risk factor for febrile urinary tract infection. This study revealed that about two-thirds of patients with persistent vesicoureteral reflux were free of febrile urinary tract infection during 5 years of active surveillance. Those with dilated vesicoureteral reflux on followup voiding cystourethrogram are at significantly greater risk for febrile urinary tract infection. Accordingly active surveillance, especially in patients with nondilated vesicoureteral reflux on followup voiding cystourethrogram, seems to be a safe option even in children who have not yet been toilet trained. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  5. HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin.

    Science.gov (United States)

    Abbate, Isabella; Lo Iacono, Oreste; Di Stefano, Rosa; Cappiello, Giuseppina; Girardi, Enrico; Longo, Roberta; Ferraro, Donatella; Antonucci, Giorgio; Di Marco, Vito; Solmone, Mariacarmela; Craxì, Antonio; Ippolito, Giuseppe; Capobianchi, Maria R

    2004-05-01

    HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV. HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.

  6. Enhanced mutagenesis of UV-irradiated simian virus 40 occurs in mitomycin C-treated host cells only at a low multiplicity of infection

    International Nuclear Information System (INIS)

    Sarasin, A.; Benoit, A.

    1986-01-01

    Treatment of monkey kidney cells with mitomycin C (MMC) 24 h prior to infection with UV-irradiated simian virus 40 (SV40) enhanced both virus survival and virus mutagenesis. The use of SV40 as a biological probe has been taken as an easy method to analyse SOS response of mammalian cells to the stress caused by DNA damage or inhibition of DNA replication. The mutation assay we used was based on the reversion from a temperature-sensitive phenotype (tsA58 mutant) to a wild-type phenotype. The optimal conditions for producing enhanced survival and mutagenesis in the virus progeny were determined with regard to the multiplicity of infection (MOI). Results showed that the level of enhanced mutagenesis observed for UV-irradiated virus grown in MMC-treated cells was an inverse function of the MOI, while enhanced survival was observed at nearly the same level regardless of the MOI. For the unirradiated virus, almost no increase in the mutation of virus progeny issued from MMC-treated cells was observed, while a small amount of enhanced virus survival was obtained. These results show that enhanced virus mutagenesis and enhanced virus survival can be dissociated under some experimental conditions. Enhanced virus mutagenesis, analogous to the error-prone replication of phages in SOS-induced bacteria, was observed, at least for SV40, only when DNA of both virus and host cells was damaged and when infection occurred with a small number of viral particles. We therefore hypothesize that an error-prone replication mode of UV-damaged templates is observed in induced monkey kidney cells

  7. Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence

    Directory of Open Access Journals (Sweden)

    Lwetoijera Dickson W

    2009-12-01

    Full Text Available Abstract Background Entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana isolates have been shown to infect and reduce the survival of mosquito vectors. Methods Here four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates M. anisopliae ICIPE-30 and B. bassiana I93-925 on infection and survival rates of female Anopheles gambiae sensu stricto. Test concentrations and exposure times ranged between 1 × 107 - 4 × 1010 conidia m-2 and 15 min - 6 h. In co-formulations, 2 × 1010 conidia m-2 of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 × 109, 2 × 1010 or 4 × 1010. Results Mosquito survival varied with conidia concentration; 2 × 1010 conidia m-2 was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d. Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence. Conclusion Both fungus isolates are effective and persistent at low concentrations and short exposure times.

  8. Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections.

    Science.gov (United States)

    Khare, Sangeeta; Drake, Kenneth L; Lawhon, Sara D; Nunes, Jairo E S; Figueiredo, Josely F; Rossetti, Carlos A; Gull, Tamara; Everts, Robin E; Lewin, Harris A; Adams, Leslie Garry

    It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer's patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

  9. Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection

    International Nuclear Information System (INIS)

    Yoneda, T.; Urade, M.; Sakuda, M.; Miyazaki, T.

    1986-01-01

    We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of 125 I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound 125 I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients

  10. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  11. The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection.

    Science.gov (United States)

    Eschlimann, Marine; Malvé, Brice; Velay, Aurélie; Fenaux, Honorine; Berger, Sibel; Frippiat, Jean-Pol; Zoulim, Fabien; Bensenane, Mouni; Bronowicki, Jean-Pierre; Goehringer, François; May, Thierry; Jeulin, Hélène; Schvoerer, Evelyne

    2017-09-01

    More than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3-16%). HBV envelope variability was investigated according to HBsAg persistence. The cohort consisted of 15 HBV genotype A-infected patients divided into "resolvers", with HBsAg clearance, and "non-resolvers", with HBsAg persistence and in subgroups: acute (n=5, AHBV) or chronic infection (n=4, CHBV) and HBV/HIV coinfection (n=6, CHBV/HIV). HBV S and preS sequences were studied by direct and ultra-deep sequencing. Amino acid sequences were analyzed with bioinformatics for predicted antigenicity. In S gene, the complexity was lower in AHBV than in chronic-infected patients (p=0.046). Major mutations, detected using direct sequencing, were more frequent in AHBV developing chronicity (p=0.01) than in AHBV resolvers. In the Major Hydrophilic Region, more frequent mutations were observed in non-resolvers versus resolvers (p=0.047) and non-resolvers tended to have more haplotypes with a reduced predicted antigenicity (p=0.07). Most of the mutations in preS/S region were found rather in epitopic than in non-epitopic areas (p=0.025). Interestingly, the mutation sY161F found in 3/8 non-resolvers was associated with a decrease in predicted antigenicity (28%; AnTheProt). HBsAg persistence was correlated with mutations and deletions in areas playing a key role in immune recognition. These data suggest that variability in HBV envelope could favor immune escape in various clinical settings of HBV genotype A-infected patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Persistent blood stream infection in patients supported with a continuous-flow left ventricular assist device is associated with an increased risk of cerebrovascular accidents.

    Science.gov (United States)

    Trachtenberg, Barry H; Cordero-Reyes, Andrea M; Aldeiri, Molham; Alvarez, Paulino; Bhimaraj, Arvind; Ashrith, Guha; Elias, Barbara; Suarez, Erik E; Bruckner, Brian; Loebe, Matthias; Harris, Richard L; Zhang, J Yi; Torre-Amione, Guillermo; Estep, Jerry D

    2015-02-01

    Common adverse events in patients supported with Continuous-flow left ventricular assist devices (CF-LVAD) include infections and cerebrovascular accidents (CVA). Some studies have suggested a possible association between blood stream infection (BSI) and CVA. Medical records of patients who received Heartmate II (HMII) CF-LVADs in 2008-2012 at a single center were reviewed. CVA was categorized as either hemorrhagic (HCVA) or ischemic (ICVA). BSI was divided into persistent (pBSI) and nonpersistent (non-pBSI). pBSI was defined as BSI with the same organism on repeated blood culture >72 hours from initial blood culture despite antibiotics. Univariate and multivariate analyses were performed to determine predictors. A total of 149 patients had HMII implanted; 76% were male, and the overall mean age was 55.4 ± 13 years. There were a total of 19 (13%) patients who had CVA (7 HCVA and 12 ICVA) at a median of 295 days (range 5-1,096 days) after implantation. There were a total of 28 (19%) patients with pBSI and 17 (11%) patients with non-pBSI. Patients with pBSI had a trend toward greater BMI (31 kg/m(2) vs 27 kg/m(2); P = .09), and longer duration of support (1,019 d vs 371 d; P < .001) compared with those with non-pBSI. Persistent BSI was associated with an increased risk of mortality and with all-cause CVA on multivariate analysis (odds ratio [OR] 5.97; P = .003) as well as persistent Pseudomonas aeruginosa infection (OR 4.54; P = .048). Persistent BSI is not uncommon in patients supported by CF-LVAD and is highly associated with all-cause CVA and increased all-cause mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Clearance of a persistent Picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

    Science.gov (United States)

    Immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in distinct microanatomic compartments of the bovine nasopharynx were investigated using quantitative RT-PCR and whole transcriptome microarray. Analysis of tissue samples obtained during ...

  14. Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil.

    Science.gov (United States)

    Malta, Fernanda; Gaspareto, Karine Vieira; Lisboa-Neto, Gaspar; Carrilho, Flair José; Mendes-Correa, Maria Cássia; Pinho, João Renato Rebello

    2017-11-13

    Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.

  15. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

    Science.gov (United States)

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  16. Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study.

    Science.gov (United States)

    Oriol, Isabel; Sabé, Núria; Simonetti, Antonella F; Lladó, Laura; Manonelles, Anna; González, Jose; Tubau, Fe; Carratalà, Jordi

    2017-09-01

    To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time. © 2017 Steunstichting ESOT.

  17. Resolution of HBV infection occurs sooner than recovery of renal disease in adult serum HBsAg-negative HBV-associated glomerulonephritis.

    Science.gov (United States)

    Xu, Fang; Wang, Chong; Shi, Xiaoju; Hou, Jie; Guo, Xiaolin; Gao, Pujun

    2018-05-02

    Most cases of hepatitis B virus-associated glomerulonephritis (HBV-GN) occur in children and present with serum HBsAg positivity. Few studies have investigated adult HBV-GN patients who are serum HBsAg-negative. This study aimed to determine the clinical and pathological features of serum HBsAg-negative adult HBV-GN patients. Clinical, pathologic and laboratory findings were collected and analyzed in a cohort of 27 adult HBV-GN patients who were serum HBsAg negative upon diagnosis. The study population included mostly men of middle age (40-59 years). Clinically, patients presented with nephrotic syndrome. Serum IgG levels were low, while serum IgM, IgA, C3, and C4 levels as well as liver and renal function tests were normal in most or all patients. Among the 27 patients, 21 tested positively for HBV antibodies. MN was the dominant pathological form on kidney biopsy. In addition, only a few patients showed a "full house" staining pattern and renal immune deposit of C1q. Serum HBsAg negative HBV-GN may represent a late stage of HBV infection. We recommend routine testing for HBV markers on renal biopsy in regions where HBV is prevalent, even when tests for serum HBV markers are negative. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Humoral immune-response against human cytomegalovirus (hcmv)-specific proteins after hcmv infection in lung transplantation as detected with recombinant and naturally-occurring proteins

    NARCIS (Netherlands)

    van Zanten, J; Harmsen, M. C.; van der Giessen, M.; van der Bij, W; Prop, J.; de Leij, L; The, T. Hauw

    The humoral immune response to four intracellularly located cytomegalovirus (CMV) proteins was studied in 15 lung transplant recipients experiencing active CMV infections. Five patients had primary infections, and 10 had secondary infections. Antibodies of the immunoglobulin M (IgM) and IgG classes

  19. Efficacy of a high free iodine barrier teat disinfectant for the prevention of naturally occurring new intramammary infections and clinical mastitis in dairy cows.

    Science.gov (United States)

    Martins, C M M R; Pinheiro, E S C; Gentilini, M; Benavides, M Lopez; Santos, M V

    2017-05-01

    Using a natural exposure trial design, the goal of our study was to evaluate the clinical efficacy of an iodine teat disinfectant with barrier properties and a high level of free iodine relative to a conventional iodine teat disinfectant with no barrier properties and low levels of free iodine. During the 18 wk of the trial, quarter milk samples were collected every 2 wk from 385 dairy cows from 2 herds. Cows on both farms were assigned in a balanced way according to milk yield, number of lactation, days in milk, somatic cell count (SCC) and microbiology culture pretrial into one of following groups: nonbarrier post milking teat disinfectant (NBAR; n = 195 cows; 747 quarters) or barrier postmilking teat disinfectant (BAR; n = 190 cows; 728 quarters). Afterward, at each scoring date every 2 wk, milk SCC was quantified in samples from all mammary quarters and microbiologic culture was only performed on milk samples with SCC >200,000 cells/mL for multiparous cows and SCC >100,000 cells/mL for primiparous cows. A new intramammary infection (NIMI) was defined when a quarter had milk SCC 200,000 cells/mL for multiparous cows and >100,000 cells/mL for primiparous cows, and positive microorganism isolation. A quarter could have several NIMI, but only 1 case per specific pathogen was considered. The most frequently isolated microorganism group on both farms was Streptococcus spp. (6.25% of total mammary quarters), followed by coagulase-negative staphylococci (3.6%) and Corynebacterium spp. (1.5%). In the present study, an interaction occurred between treatment and week of trial on the incidence risk of NIMI. Quarters disinfected with BAR had 54 and 37% lower odds of NIMI than quarters disinfected with NBAR at 8 and 16 wk of the trial, respectively; whereas at other weeks of the study both products had similar incidence risks of NIMI. Overall, teats disinfected with BAR had 46% lower odds of acquiring a clinical mastitis than those disinfected with NBAR. We concluded that

  20. Retrospective study of the influence of HPV persistence on outcomes among women with high-risk HPV infections and negative cytology.

    Science.gov (United States)

    Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Martinelli, Fabio; Signorelli, Mauro; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Scaffa, Cono; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

    2017-07-01

    To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia. The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed. There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses. Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. © 2017 International Federation of Gynecology and Obstetrics.

  1. Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012-2015: a retrospective cohort study.

    Science.gov (United States)

    Hananta, I Putu Yuda; De Vries, Henry John Christiaan; van Dam, Alje P; van Rooijen, Martijn Sebastiaan; Soebono, Hardyanto; Schim van der Loeff, Maarten Franciscus

    2017-11-01

    Infection of Neisseria gonorrhoeae in the pharynx (pharyngeal Ng) is associated with gonococcal transmission and development of antimicrobial resistance. We assessed proportion of and determinants for persistence after treatment of pharyngeal Ng. At the STI clinic of Amsterdam, the Netherlands, females-at-risk and men who have sex with men are routinely screened for pharyngeal Ng using an RNA-based nucleic acid amplification test (NAAT; Aptima Combo 2). Patients with pharyngeal Ng were invited for a test-of-cure (TOC) 7 days after treatment with a 500 mg ceftriaxone intramuscularly. We retrospectively examined medical records of patients with pharyngeal Ng (January 2012-August 2015) who returned for a TOC 7-28 days after treatment. Persistence was defined as a positive NAAT at TOC. Out of 2204 pharyngeal Ng cases recorded in the study period, 781 cases (median time between first treatment and TOC of 8 (IQR 7-12) days) were included in the analysis. Persistence after treatment was found in 36 (4.6%) and was less likely among patients who received ceftriaxone in combination with other antibiotics (vs monotherapy) (adjusted OR (aOR) 0.36, 95% CI 0.12 to 1.04) and with longer time from treatment to TOC (aOR 0.74, 95% CI 0.60 to 0.90, per extra day). In those with a TOC 15-28 days after treatment, Ng persisted in only 1.0% (1/105 cases). A small proportion of pharyngeal Ng persists despite appropriate treatment. Combining ceftriaxone with other antibiotics appears to lead to faster clearance. A TOC for pharyngeal Ng 7 days after treatment may be too soon. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012–2015: a retrospective cohort study

    Science.gov (United States)

    De Vries, Henry John Christiaan; van Dam, Alje P; van Rooijen, Martijn Sebastiaan; Soebono, Hardyanto; Schim van der Loeff, Maarten Franciscus

    2017-01-01

    Introduction Infection of Neisseria gonorrhoeae in the pharynx (pharyngeal Ng) is associated with gonococcal transmission and development of antimicrobial resistance. We assessed proportion of and determinants for persistence after treatment of pharyngeal Ng. Methods At the STI clinic of Amsterdam, the Netherlands, females-at-risk and men who have sex with men are routinely screened for pharyngeal Ng using an RNA-based nucleic acid amplification test (NAAT; Aptima Combo 2). Patients with pharyngeal Ng were invited for a test-of-cure (TOC) 7 days after treatment with a 500 mg ceftriaxone intramuscularly. We retrospectively examined medical records of patients with pharyngeal Ng (January 2012–August 2015) who returned for a TOC 7–28 days after treatment. Persistence was defined as a positive NAAT at TOC. Results Out of 2204 pharyngeal Ng cases recorded in the study period, 781 cases (median time between first treatment and TOC of 8 (IQR 7–12) days) were included in the analysis. Persistence after treatment was found in 36 (4.6%) and was less likely among patients who received ceftriaxone in combination with other antibiotics (vs monotherapy) (adjusted OR (aOR) 0.36, 95% CI 0.12 to 1.04) and with longer time from treatment to TOC (aOR 0.74, 95% CI 0.60 to 0.90, per extra day). In those with a TOC 15–28 days after treatment, Ng persisted in only 1.0% (1/105 cases). Conclusion A small proportion of pharyngeal Ng persists despite appropriate treatment. Combining ceftriaxone with other antibiotics appears to lead to faster clearance. A TOC for pharyngeal Ng 7 days after treatment may be too soon. PMID:28822976

  3. The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells

    OpenAIRE

    Djekic, Aleksandra; M?ller, Anne

    2016-01-01

    VacA is a pore-forming toxin that has long been known to induce vacuolization in gastric epithelial cells and to be linked to gastric disorders caused by H. pylori infection. Its role as a major colonization and persistence determinant of H. pylori is less well-understood. The purpose of this review is to discuss the various target cell types of VacA and its mechanism of action; specifically, we focus on the evidence showing that VacA targets myeloid cells and T-cells to directly and indirect...

  4. Persistent bovine pestivirus infection localized in the testes of an immuno-competent, non-viraemic bull

    NARCIS (Netherlands)

    Voges, H.; Horner, G.W.; Rowe, S.; Wellenberg, G.J.

    1998-01-01

    A post-pubertal bull on an artificial insemination station was found to be persistently shedding bovine viral diarrhoea virus (BVDV) in semen over a period of eleven months, while demonstrating no viraemia. Circulating antibodies to BVDV were consistently high, suggesting that the immune system was

  5. HIV-infected children living in Central Africa have low persistence of antibodies to vaccines used in the Expanded Program on Immunization.

    Directory of Open Access Journals (Sweden)

    Mathurin C Tejiokem

    Full Text Available BACKGROUND: The Expanded Program on Immunization (EPI is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART should considerably prolong their life expectancy. METHODS AND PRINCIPAL FINDINGS: To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP, the measles and the oral polio (OPV vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001. We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4(+ T cells <25%. CONCLUSIONS AND SIGNIFICANCE: Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4(+ T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the

  6. Human papillomavirus (HPV types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

    Directory of Open Access Journals (Sweden)

    Ferenczy Alex

    2010-11-01

    Full Text Available Abstract Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.

  7. Translocation of the B cell receptor to lipid rafts is inhibited in B cells from BLV-infected, persistent lymphocytosis cattle

    International Nuclear Information System (INIS)

    Hamilton, Valerie T.; Stone, Diana M.; Cantor, Glenn H.

    2003-01-01

    Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5 + , IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5 + B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis

  8. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    Science.gov (United States)

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (Paged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; Page and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  9. Characterization of thymus-associated lymphoid depletion in bovine calves acutely or persistently infected with bovine viral diarrhea virus 1, bovine viral diarrhea 2 or HoBi-like pestivirus

    Science.gov (United States)

    Viruses from recognized pestivirus species bovine viral diarrhea 1 (BVDV-1) and BVDV-2 and the proposed pestivirus species HoBi-like virus infect primarily cattle. Exposure of cattle to these viruses can lead to either acute or persistent infections depending on the timing and status of the animal ...

  10. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

    Science.gov (United States)

    Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

    2018-04-24

    To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

  11. The role of biofilms in persistent infections and factors involved in ica-independent biofilm development and gene regulation in Staphylococcus aureus.

    Science.gov (United States)

    Figueiredo, Agnes Marie Sá; Ferreira, Fabienne Antunes; Beltrame, Cristiana Ossaille; Côrtes, Marina Farrel

    2017-09-01

    Staphylococcus aureus biofilms represent a unique micro-environment that directly contribute to the bacterial fitness within hospital settings. The accumulation of this structure on implanted medical devices has frequently caused the development of persistent and chronic S. aureus-associated infections, which represent an important social and economic burden worldwide. ica-independent biofilms are composed of an assortment of bacterial products and modulated by a multifaceted and overlapping regulatory network; therefore, biofilm composition can vary among S. aureus strains. In the microniches formed by biofilms-produced by a number of bacterial species and composed by different structural components-drug refractory cell subpopulations with distinct physiological characteristics can emerge and result in therapeutic failures in patients with recalcitrant bacterial infections. In this review, we highlight the importance of biofilms in the development of persistence and chronicity in some S. aureus diseases, the main molecules associated with ica-independent biofilm development and the regulatory mechanisms that modulate ica-independent biofilm production, accumulation, and dispersion.

  12. Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx.

    Directory of Open Access Journals (Sweden)

    Michael Eschbaumer

    Full Text Available In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467 had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97, indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E2 production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.

  13. Chronic Nosema ceranae infection inflicts comprehensive and persistent immunosuppression and accelerated lipid loss in host Apis mellifera honey bees.

    Science.gov (United States)

    Li, Wenfeng; Chen, Yanping; Cook, Steven C

    2018-05-01

    Nosema ceranae is an intracellular microsporidian parasite of the Asian honey bee Apis cerana and the European honey bee Apis mellifera. Until relatively recently, A. mellifera honey bees were naïve to N. ceranae infection. Symptoms of nosemosis, or Nosema disease, in the infected hosts include immunosuppression, damage to gut epithelium, nutrient and energetic stress, precocious foraging and reduced longevity of infected bees. Links remain unclear between immunosuppression, the symptoms of nutrient and energetic stress, and precocious foraging behavior of hosts. To clarify physiological connections, we inoculated newly emerged A. mellifera adult workers with N. ceranae spores, and over 21 days post inoculation (21 days pi), gauged infection intensity and quantified expression of genes representing two innate immune pathways, Toll and Imd. Additionally, we measured each host's whole-body protein, lipids, carbohydrates and quantified respirometric and activity levels. Results show sustained suppression of genes of both humorally regulated immune response pathways after 6 days pi. At 7 days pi, elevated protein levels of infected bees may reflect synthesis of antimicrobial peptides from an initial immune response, but the lack of protein gain compared with uninfected bees at 14 days pi may represent low de novo protein synthesis. Carbohydrate data do not indicate that hosts experience severe metabolic stress related to this nutrient. At 14 days pi infected honey bees show high respirometric and activity levels, and corresponding lipid loss, suggesting lipids may be used as fuel for increased metabolic demands resulting from infection. Accelerated lipid loss during nurse honey bee behavioral development can have cascading effects on downstream physiology that may lead to precocious foraging, which is a major factor driving colony collapse. Published by Elsevier Ltd.

  14. E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

    Directory of Open Access Journals (Sweden)

    Yueting Zheng

    2016-01-01

    Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

  15. On the causes of persistent apical periodontitis: a review.

    Science.gov (United States)

    Nair, P N R

    2006-04-01

    Apical periodontitis is a chronic inflammatory disorder of periradicular tissues caused by aetiological agents of endodontic origin. Persistent apical periodontitis occurs when root canal treatment of apical periodontitis has not adequately eliminated intraradicular infection. Problems that lead to persistent apical periodontitis include: inadequate aseptic control, poor access cavity design, missed canals, inadequate instrumentation, debridement and leaking temporary or permanent restorations. Even when the most stringent procedures are followed, apical periodontitis may still persist as asymptomatic radiolucencies, because of the complexity of the root canal system formed by the main and accessory canals, their ramifications and anastomoses where residual infection can persist. Further, there are extraradicular factors -- located within the inflamed periapical tissue -- that can interfere with post-treatment healing of apical periodontitis. The causes of apical periodontitis persisting after root canal treatment have not been well characterized. During the 1990s, a series of investigations have shown that there are six biological factors that lead to asymptomatic radiolucencies persisting after root canal treatment. These are: (i) intraradicular infection persisting in the complex apical root canal system; (ii) extraradicular infection, generally in the form of periapical actinomycosis; (iii) extruded root canal filling or other exogenous materials that cause a foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue healing of the lesion. This article provides a comprehensive overview of the causative factors of non-resolving periapical lesions that are seen as asymptomatic radiolucencies post-treatment.

  16. Persistence of specific antibody response in different experimental infections of mice with Toxocara canis larvae Persistência da resposta humoral em camundongos experimentalmente infectados com larvas de Toxocara canis

    Directory of Open Access Journals (Sweden)

    Pedro Paulo Chieffi

    1995-06-01

    Full Text Available Anti-Toxocara antibody production and persistence were studied in experimental infections of BALB/c mice, according to three different schedules: Group I (GI - 25 mice infected with 200 T. canis eggs in a single dose; Group II (GII 25 mice infected with 150 T. canis eggs given in three occasions, 50 in the 1st, 50 in the 5th and 50 in the 8th days; Group III (GIII - 25 mice also infected with 150 T. canis eggs, in three 50 eggs portions given in the 1st, 14th and 28th days. A 15 mice control group (GIV was maintained without infection. In the 30th, 50th, 60th, 75th, 105th and 180th post-infection days three mice of the GI, GII and GIII groups and two mice of the control group had been sacrificed and exsanguinated for sera obtention. In the 360th day the remainder mice of the four groups were, in the same way, killed and processed. The obtained sera were searched for the presence of anti-Toxocara antibodies by an ELISA technique, using T. canis larvae excretion-secretion antigen. In the GI and GII, but not in the GIII, anti-Toxocara antibodies had been found, at least, up to the 180th post-infection day. The GIII only showed anti-Toxocara antibodies, at significant level, in the 30th post-infection day.Estudou-se a cinética de anticorpos anti-Toxocara em camundongos BALB/c infectados experimentalmente segundo três esquemas: Grupo I (GI: 25 camundongos infectados com dose única de 200 ovos embrionados de T. canis; grupo II (GII: 25 camundongos infectados com 150 ovos embrionados de T. canis, divididos em três doses de 50 ovos, administrados no 1º, 5º e 8º dias; Grupo III (GIII: 25 camundongos infectados com 150 ovos embrionados de T. canis, administrados em três doses de 50 ovos no 1º, 14º e 28º dias. Um grupo de 15 camundongos foi mantido nas mesmas condições, porém sem infecção, constituindo o grupo controle (GIV. No 30º, 50º, 60º, 75º, 105º e 180º dias pós-infecção três camundongos dos grupos GI, GII e GIII e dois do

  17. Partial-limb salvage after persistent infection in the distal femoral prosthesis: straight-plasty - a novel technique

    International Nuclear Information System (INIS)

    Kundu, Z. S.; Gupta, V.; Gogna, P.

    2014-01-01

    A 35 years old female had giant cell tumour (GCT) of the distal femur for which wide resection and distal femoral endoprosthetic replacement was performed. Massive infection of prosthesis required removal and replacement of the prosthesis with nail antibiotic cement spacer, which also proved to be futile. Ultimately the whole of the infected thigh had to be excised. The limb could be preserved partially using straight-plasty instead of amputation. Patient is well rehabilitated and doing well at a follow-up of 3 years. (author)

  18. Characterization of thymus-associated lymphoid depletion in bovine calves acutely or persistently infected with bovine viral diarrhea virus 1, bovine viral diarrhea virus 2 or HoBi-like pestivirus.

    Science.gov (United States)

    Falkenberg, Shollie M; Bauermann, Fernando V; Ridpath, Julia F

    2017-11-01

    Naïve pregnant cattle exposed to pestiviruses between 40-125 days of gestation can give birth to persistently infected (PI) calves. Clinical presentation and survivability, in PI cattle, is highly variable even with the same pestivirus strain whereas the clinical presentation in acute infections is more uniform with severity of symptoms being primarily a function of virulence of the infecting virus. The aim of this study was to compare thymic depletion, as measured by comparing the area of the thymic cortex to the medulla (corticomedullary ratio), in acute and persistent infections of the same pestivirus isolate. The same general trends were observed with each pestivirus isolate. Thymic depletion was observed in both acutely and persistently infected calves. The average thymic depletion observed in acutely infected calves was greater than that in age matched PI calves. PI calves, regardless of infecting virus, revealed a greater variability in amount of depletion compared to acutely infected calves. A trend was observed between survivability and depletion of the thymus, with PI calves surviving less than 5 weeks having lower corticomedullary ratios and greater depletion. This is the first study to compare PI and acutely infected calves with the same isolates as well as to evaluate PI calves based on survivability. Further, this study identified a quantifiable phenotype associated with potential survivability.

  19. Excretion in feces and mucosal persistence of Salmonella ser. Typhimurium in pigs subclinically infected with Oesophagostomum spp

    DEFF Research Database (Denmark)

    Steenhard, N.R.; Jensen, Tim Kåre; Baggesen, Dorte Lau

    2002-01-01

    ; group B was given 0 dentatum, 0 quadrispinulatum, and S Typhimurium; and group C was given STyphimurium only. Pigs in groups A and B were trickle infected with Oesophagostomum spp 3 times weekly throughout the study. After 19 days, groups B and C were inoculated once with STyphimurium. One pig from each...

  20. Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis

    Directory of Open Access Journals (Sweden)

    Michell Stephen L

    2011-01-01

    Full Text Available Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella infection models. Results B. pseudomallei strains 576 and K96243, which have low median lethal dose (MLD values in mice, were able to replicate and induce cellular damage in macrophages and caused rapid death of G. mellonella. In contrast, B. pseudomallei strain 708a, which is attenuated in mice, showed reduced replication in macrophages, negligible cellular damage and was avirulent in G. mellonella larvae. B. thailandensis isolates were less virulent than B. pseudomallei in all of the models tested. However, we did record strain dependent differences. B. oklahomensis isolates were the least virulent isolates. They showed minimal ability to replicate in macrophages, were unable to evoke actin-based motility or to form multinucleated giant cells and were markedly attenuated in G. mellonella compared to B. thailandensis. Conclusions We have shown that the alternative infection models tested here, namely macrophages and Galleria mellonella, are able to distinguish between strains of B. pseudomallei, B. thailandensis and B. oklahomensis and that these differences reflect the observed virulence in murine infection models. Our results indicate that B. oklahomensis is the least pathogenic of the species investigated. They also show a correlation between isolates of B. thailandensis associated with human infection and virulence in macrophage and Galleria infection models.

  1. Surgical site infections following operative management of cervical spondylotic myelopathy: prevalence, predictors of occurence, and influence on peri-operative outcomes.

    Science.gov (United States)

    Jalai, C M; Worley, N; Poorman, G W; Cruz, D L; Vira, S; Passias, P G

    2016-06-01

    Studies have examined infection rates following spine surgery and their relationship to post-operative complications and increased length of stay. Few studies, however, have investigated predictors of infection, specifically in the setting of operative intervention for cervical spondylotic myelopathy (CSM). This study aims to identify the incidence and factors predictive of infection amongst this cohort. This study performed a retrospective review of the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Patients included those treated surgically for CSM (ICD-9 code 721.1) from 2010 to 2012. Patient demographics and surgical data were collected with outcome variables including the occurrence of one of the following surgical site infections (SSIs) within 30 days of index operation: superficial SSI, deep incisional SSI, and organ/space SSI. 3057 patients were included in this analysis. Overall infection rate was 1.15 % (35/3057), of which 54.3 % (19/35) were superficial SSIs, 28.6 % (10/35) were deep incisional SSI, and 20 % (7/35) were peri-spinal SSI. Logistic regression revealed factors associated with SSI included: higher BMI [OR 1.162 (CI 1.269-1.064), p = 0.001] and operative time ≥208 min [OR 4.769 (CI 20.220-1.125), p = 0.034]. The overall SSI rate for the examined CSM cohort was 1.15 %. This study identified increased BMI and operative time ≥208 min as predictors of infection in surgical CSM patients. This information should be carefully considered in delivering patient education and future efforts to optimize risk in CSM patients indicated for surgical intervention.

  2. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

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

    Science.gov (United States)

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

    2013-01-01

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

  4. Highly differentiated, resting gn-specific memory CD8+ T cells persist years after infection by andes hantavirus.

    Directory of Open Access Journals (Sweden)

    Tobias Manigold

    2010-02-01

    Full Text Available In man, infection with South American Andes virus (ANDV causes hantavirus cardiopulmonary syndrome (HCPS. HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-gamma ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3(+CD8(+ T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473 years after the acute infection. Remarkably, Gn(465-473-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+CD27(-CD28(-CCR7(-CD127(- effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T

  5. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

    Science.gov (United States)

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  6. Activation of type I and III interferon signalling pathways occurs in lung epithelial cells infected with low pathogenic avian influenza viruses.

    Directory of Open Access Journals (Sweden)

    Richard Sutejo

    Full Text Available The host response to the low pathogenic avian influenza (LPAI H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture.

  7. The NSs protein of tomato spotted wilt virus is required for persistent infection and transmission by Frankliniella occidentalis.

    Science.gov (United States)

    Margaria, P; Bosco, L; Vallino, M; Ciuffo, M; Mautino, G C; Tavella, L; Turina, M

    2014-05-01

    Tomato spotted wilt virus (TSWV) is the type member of tospoviruses (genus Tospovirus), plant-infecting viruses that cause severe damage to ornamental and vegetable crops. Tospoviruses are transmitted by thrips in the circulative propagative mode. We generated a collection of NSs-defective TSWV isolates and showed that TSWV coding for truncated NSs protein could not be transmitted by Frankliniella occidentalis. Quantitative reverse transcription (RT)-PCR and immunostaining of individual insects detected the mutant virus in second-instar larvae and adult insects, demonstrating that insects could acquire and accumulate the NSs-defective virus. Nevertheless, adults carried a significantly lower viral load, resulting in the absence of transmission. Genome sequencing and analyses of reassortant isolates showed genetic evidence of the association between the loss of competence in transmission and the mutation in the NSs coding sequence. Our findings offer new insight into the TSWV-thrips interaction and Tospovirus pathogenesis and highlight, for the first time in the Bunyaviridae family, a major role for the S segment, and specifically for the NSs protein, in virulence and efficient infection in insect vector individuals. Our work is the first to show a role for the NSs protein in virus accumulation in the insect vector in the Bunyaviridae family: demonstration was obtained for the system TSWV-F. occidentalis, arguably one of the most damaging combination for vegetable crops. Genetic evidence of the involvement of the NSs protein in vector transmission was provided with multiple approaches.

  8. Persistence of foot-and mouth disease virus in ruminants

    DEFF Research Database (Denmark)

    Stenfeldt, Carolina; Belsham, Graham; Tjørnehøj, Kirsten

    squamous epithelia of the coronary bands and oral cavity within a few days of infection. Viremia occurs within 2-3 days of infection, but is rapidly cleared through the effect of circulating antibodies of the adaptive immune response. The host response involves initial activation of the innate immune...... response, with activation and recruitment of effector-cells, and subsequent activation of T- and B-cells, leading to the production of circulating antibodies, as well as activation of cytotoxic T-cells. In ruminants, approximately 50% of animals infected with FMDV develop into persistently infected carrier...... animals, with intermittent excretion of live virus, whilst remaining animals clear the infection effectively. Previous experiments have indicated that the site of persistent viral replication is located in pharyngeal lymphoid tissue, as well as the basal epithelia of the dorsal soft palate...

  9. Naturally Occurring Frameshift Mutations in the tvb Receptor Gene Are Responsible for Decreased Susceptibility of Chicken to Infection with Avian Leukosis Virus Subgroups B, D, and E.

    Science.gov (United States)

    Li, Xinjian; Chen, Weiguo; Zhang, Huanmin; Li, Aijun; Shu, Dingming; Li, Hongxing; Dai, Zhenkai; Yan, Yiming; Zhang, Xinheng; Lin, Wencheng; Ma, Jingyun; Xie, Qingmei

    2018-04-15

    The group of highly related avian leukosis viruses (ALVs) in chickens are thought to have evolved from a common retroviral ancestor into six subgroups, A to E and J. These ALV subgroups use diverse cellular proteins encoded by four genetic loci in chickens as receptors to gain entry into host cells. Hosts exposed to ALVs might be under selective pressure to develop resistance to ALV infection. Indeed, resistance alleles have previously been identified in all four receptor loci in chickens. The tvb gene encodes a receptor, which determines the susceptibility of host cells to ALV subgroup B (ALV-B), ALV-D, and ALV-E. Here we describe the identification of two novel alleles of the tvb receptor gene, which possess independent insertions each within exon 4. The insertions resulted in frameshift mutations that reveal a premature stop codon that causes nonsense-mediated decay of the mutant mRNA and the production of truncated Tvb protein. As a result, we observed that the frameshift mutations in the tvb gene significantly lower the binding affinity of the truncated Tvb receptors for the ALV-B, ALV-D, and ALV-E envelope glycoproteins and significantly reduce susceptibility to infection by ALV-B, ALV-D and ALV-E in vitro and in vivo Taken together, these findings suggest that frameshift mutation can be a molecular mechanism of reducing susceptibility to ALV and enhance our understanding of virus-host coevolution. IMPORTANCE Avian leukosis virus (ALV) once caused devastating economic loss to the U.S. poultry industry prior the current eradication schemes in place, and it continues to cause severe calamity to the poultry industry in China and Southeast Asia, where deployment of a complete eradication scheme remains a challenge. The tvb gene encodes the cellular receptor necessary for subgroup B, D, and E ALV infection. Two tvb allelic variants that resulted from frameshift mutations have been identified in this study, which have been shown to have significantly reduced

  10. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

    Science.gov (United States)

    Katki, Hormuzd A; Cheung, Li C; Fetterman, Barbara; Castle, Philip E; Sundaram, Rajeshwari

    2015-10-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

  11. Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2008-04-29

    CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

  12. Enhanced Effector Function of CD8+ T Cells From Healthy Controls and HIV-Infected Patients Occurs Through Thrombin Activation of Protease-Activated Receptor 1

    Science.gov (United States)

    Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B.; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M.; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta

    2013-01-01

    Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4+ and CD8+ T lymphocytes expressed PAR-1 and that expression was increased in CD8+ T cells from human immunodeficiency virus (HIV)–infected patients. Thrombin enhanced cytokine secretion in CD8+ T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8+ T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines. PMID:23204166

  13. Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1.

    Science.gov (United States)

    Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H Clifford; Catalfamo, Marta

    2013-02-15

    Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.

  14. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Directory of Open Access Journals (Sweden)

    Sama Adnan

    2016-12-01

    Full Text Available Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  15. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Science.gov (United States)

    Adnan, Sama; Reeves, R Keith; Gillis, Jacqueline; Wong, Fay E; Yu, Yi; Camp, Jeremy V; Li, Qingsheng; Connole, Michelle; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D; Li, Wenjun; Keele, Brandon F; Kozlowski, Pamela A; Desrosiers, Ronald C; Haase, Ashley T; Johnson, R Paul

    2016-12-01

    Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  16. Unusual coexistence of opportunistic lung infections in a human immunodeficiency virus positive patient suffering from persistent Pneumocystis jirovecii pneumonia: A case report

    Directory of Open Access Journals (Sweden)

    D. Ponces Bento

    2013-05-01

    Full Text Available It is well-established that HIV patients are at high risk of opportunistic infections (OI, like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP. We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA, cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy which were crucial for patient recovery. Resumo: Como é sabido, nos doentes com infeção por vírus da imunodeficiência humana (VIH existe um alto risco de ocorrência de infeções oportunistas (IO, tais como as infeções por Pneumocystis jirovecii, um agente patogénico com distribuição mundial, que provoca pneumonia intersticial (PPc. Apresentamos um caso de um doente recém-diagnosticado com infeção por VIH-1 e múltiplas IO pulmonares, incluindo uma forma persistente de PPc, aspergilose invasiva (AI, e infeções por citomegalovírus e por Mycobacterium xenopi. Descrevemos a combinação de fatores cruciais para a recuperação do doente, que incluíram a obtenção de dados laboratoriais, intervenção cirúrgica e múltipla terapêutica antimicrobiana. Keywords: Human immunodeficiency virus (HIV, Pneumocystis jirovecii Pneumonia (PcP, Opportunistic infections, Lungs, Palavras-chave: Vírus da imunodeficiência humana (VIH, Pneumonia por Pneumocystis jirovecii (PPc, Infeções oportunistas, Pulmões

  17. Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo.

    Science.gov (United States)

    Yamamoto, Brenda; Li, Min; Kesic, Matthew; Younis, Ihab; Lairmore, Michael D; Green, Patrick L

    2008-05-12

    Human T-cell leukemia virus (HTLV) type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF) II (p30 and p28, respectively) acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Deltap28) was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Deltap28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Deltap28 and the mutant virus failed to establish persistent infection. We provide direct evidence that p28 is dispensable for viral replication and cellular immortalization of

  18. Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo

    Directory of Open Access Journals (Sweden)

    Kesic Matthew

    2008-05-01

    Full Text Available Abstract Background Human T-cell leukemia virus (HTLV type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF II (p30 and p28, respectively acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. Results In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Δp28 was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Δp28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Δp28 and the mutant virus failed to establish persistent infection. Conclusion We provide direct evidence that p28 is dispensable for

  19. Molecular Evidence for the Aerial Route of Infection of Mycobacterium leprae and the Role of Asymptomatic Carriers in the Persistence of Leprosy.

    Science.gov (United States)

    Araujo, Sergio; Freitas, Larissa Oliveira; Goulart, Luiz Ricardo; Goulart, Isabela Maria Bernardes

    2016-12-01

     Leprosy persists as a public health problem. The chain of transmission and mechanism of infection are not completely understood. In the current study, we investigated the route of infection and of disease onset, from airway exposure, colonization, and bloodstream dissemination.  Mycobacterium leprae DNA was detected through quantitative polymerase chain reaction in nasal vestibule, nasal turbinate mucosa, and peripheral blood samples, along with anti-phenolic glycolipid I serology and skin tests from the same individual, from 113 leprosy patients and 104 household contacts of patients (HHCs). Bivariate statistics and multiple correspondence analysis were employed.  The rates of DNA positivity among patients were 66.4% (75 of 113) for nasal swab samples, 71.7% (81 of 113) for nasal turbinate biopsy samples, 19.5% (22 of 113) for blood samples, with seropositivity of 62.8% (71 of 113 samples) and with increasing incidences toward the multibacillary pole of the clinical spectrum. Positivity among HHCs were as follows: 49% (51 of 104) for nasal swab samples, 53.8% (56 of 104) for nasal biopsy samples, 6.7% (7 of 104) for blood samples, and 18.3% (19 of 104 samples) for anti-phenolic glycolipid I serology. During the follow-up of 5-7 years, out of 104 HHCs, 7 developed leprosy (6.7%). Risk for the disease outcome was estimated by comparing results in HHCs who develop leprosy with those not affected. Neither nasal passage nor mucosa positivity was determinant of later disease onset; however, blood presence increased the risk for disease development (relative risk/positive likelihood ratio, 5.54; 95% confidence interval, 1.30-23.62), as did seropositivity (positive likelihood ratio, 3.69 [1.67-8.16]; relative risk, 5.97 [1.45-24.5]).  Our findings strongly suggest that the aerosol route of infection and transmission is predominant and that HHCs contribute to the infection risk to themselves and probably to others. © The Author 2016. Published by Oxford

  20. Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection.

    Science.gov (United States)

    Tavares, Rita C F; Feldner, Ana C C A; Pinho, João R R; Uehara, Silvia N O; Emori, Christini T; Carvalho-Filho, Roberto J; Silva, Ivonete S S; Santana, Rúbia A F; de Castro, Vanessa F D; Castoli, Gregório T F; Cristovão, Charliana U; Ferraz, Maria L C G

    2017-07-01

    Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients: V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.

  1. Microaerophilic conditions permit to mimic in vitro events occurring during in vivo Helicobacter pylori infection and to identify Rho/Ras-associated proteins in cellular signaling.

    Science.gov (United States)

    Cottet, Sandra; Corthésy-Theulaz, Irène; Spertini, François; Corthésy, Blaise

    2002-09-13

    Molecular dissection of the mechanisms underlying Helicobacter pylori infection suffers from the lack of in vitro systems mimicking in vivo observations. A system was developed whereby human epithelial cells (Caco-2) grown as polarized monolayers and bacteria can communicate with each other under culture conditions optimal for each partner. Caco-2 cells grown on filter supports were inserted in a vertical position into diffusion chambers equilibrated with air and 5% CO(2) at their basolateral surface (aerophilic conditions) and 5% CO(2), 5% O(2), 90% N(2) (microaerophilic conditions) in the apical compartment. Remarkably, the epithelial polarized layer was stable under these asymmetric culture conditions for at least 24 h, and the presence of Caco-2 cells was necessary to maintain H. pylori growth. In contrast to previous studies conducted with non-polarized Caco-2 cells and other cell lines kept under aerophilic conditions, we found H. pylori-dependent stimulation of cytokine secretion (MCP-1 (monocyte chemoattractant protein-1), GRO-alpha (growth-regulated oncogene-alpha), RANTES (regulated on activation normal T cell expressed and secreted)). This correlated with nuclear translocation of NF-kappaB p50 and p65 subunits. Tyrosine phosphorylation of nine cellular proteins was induced or enhanced; we identified p120(RasGAP), p190(RhoGAP), p62dok (downstream of tyrosine kinases), and cortactin as H. pylori-inducible targets. Moreover, reduction of H. pylori urease expression was observed in adherent bacteria as compared with bacteria in suspension. In addition to mimicking several observations seen in the inflamed gastric mucosa, the novel in vitro system was allowed to underscore complex cellular events not seen in classical in vitro analyses of microaerophilic bacteria-epithelial cell cross-talk.

  2. Taenia solium, Taenia saginata, Taenia asiatica, their hybrids and other helminthic infections occurring in a neglected tropical diseases' highly endemic area in Lao PDR

    Science.gov (United States)

    Sato, Megumi; Yanagida, Tetsuya; Waikagul, Jitra; Pongvongsa, Tiengkham; Sako, Yasuhito; Sanguankiat, Surapol; Yoonuan, Tipparayat; Kounnavang, Sengchanh; Kawai, Satoru; Ito, Akira; Okamoto, Munehiro; Moji, Kazuhiko

    2018-01-01

    Most part of Southeast Asia is considered endemic for human-infecting Taenia tapeworms; Taenia solium, T. saginata, and T. asiatica. However, until now there was no report of the occurrence of human cases of T. asiatica in Lao PDR. This study, conducted in Savannakhet Province, Lao PDR, microscopically examined a total of 470 fecal samples by Kato Katz method and found 86% of people harboring at least one helminth. Hookworms were detected in 56% of the samples besides Opisthorchis like eggs (42%), Trichuris trichiura (27%), Ascaris spp. (14%), and Taenia spp. (4%) eggs. Serology for cysticercosis showed 6.8% positives with results varying from 3% to 14.3% in Ethnic School students and Kalouk Kao village respectively. Species-specific PCR targeting mitochondrial DNA (mtDNA) of 28 tapeworms, recovered from 16 patients, revealed T. solium (n = 2), T. saginata (n = 21), and T. asiatica (n = 5). Two patients were confirmed to be coinfected with T. saginata and T. asiatica, indicating the endemicity of the 3 human Taenia in Lao PDR. However, nucleotide sequencing of a nuclear DNA gene, DNA polymerase delta (pold) revealed that all the tapeworms identified as T. asiatica using mtDNA had T. saginata type allele at pold locus, demonstrating that they are not “pure T. asiatica” but the hybrid descendants between the two species, confirming the wide distribution of hybrids of T. saginata/ T. asiatica in Southeast Asia. The high prevalence of several helminthic NTDs in east Savannakhet area even with conventional control measures indicates the importance to establish wide and multifaceted health programs to sustainably improve the quality of life of the populations living in these communities. PMID:29420601

  3. Taenia solium, Taenia saginata, Taenia asiatica, their hybrids and other helminthic infections occurring in a neglected tropical diseases' highly endemic area in Lao PDR.

    Directory of Open Access Journals (Sweden)

    Marcello Otake Sato

    2018-02-01

    Full Text Available Most part of Southeast Asia is considered endemic for human-infecting Taenia tapeworms; Taenia solium, T. saginata, and T. asiatica. However, until now there was no report of the occurrence of human cases of T. asiatica in Lao PDR. This study, conducted in Savannakhet Province, Lao PDR, microscopically examined a total of 470 fecal samples by Kato Katz method and found 86% of people harboring at least one helminth. Hookworms were detected in 56% of the samples besides Opisthorchis like eggs (42%, Trichuris trichiura (27%, Ascaris spp. (14%, and Taenia spp. (4% eggs. Serology for cysticercosis showed 6.8% positives with results varying from 3% to 14.3% in Ethnic School students and Kalouk Kao village respectively. Species-specific PCR targeting mitochondrial DNA (mtDNA of 28 tapeworms, recovered from 16 patients, revealed T. solium (n = 2, T. saginata (n = 21, and T. asiatica (n = 5. Two patients were confirmed to be coinfected with T. saginata and T. asiatica, indicating the endemicity of the 3 human Taenia in Lao PDR. However, nucleotide sequencing of a nuclear DNA gene, DNA polymerase delta (pold revealed that all the tapeworms identified as T. asiatica using mtDNA had T. saginata type allele at pold locus, demonstrating that they are not "pure T. asiatica" but the hybrid descendants between the two species, confirming the wide distribution of hybrids of T. saginata/ T. asiatica in Southeast Asia. The high prevalence of several helminthic NTDs in east Savannakhet area even with conventional control measures indicates the importance to establish wide and multifaceted health programs to sustainably improve the quality of life of the populations living in these communities.

  4. Significado de la fiebre persistente o recurrente durante el tratamiento de la endocarditis infecciosa Clinical significance of persistent or recurrent fever during the treatment of infective endocarditis

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    José Carena

    2004-06-01

    Full Text Available Se evaluaron 81 pacientes con endocarditis infecciosa con el objeto de establecer la significación clínica de la presencia de fiebre persistente (FP y/o fiebre recurrente (FR durante el tratamiento. Un total de 46 pacientes (56.8% (Grupo 1 tuvieron FP y/o FR durante el tratamiento: 35 FP y 16 FR, que se compararon con 35 sin FP/FR (Grupo 2. No hubo diferencias en la edad, sexo, permanencia hospitalaria, origen nosocomial, demora diagnóstica y comorbilidad asociada. El compromiso aórtico (47.8 vs 34.2% y tricuspídeo (21.7 vs 11.4% y la infección por Staphylococcus aureus (55.5 vs 28% fueron más frecuentes en el Grupo 1, aunque no significativamente. El S. aureus meticilino resistente (SAMR (22.2 vs 4%, las complicaciones (95.6 vs 65.7%, la disfunción renal (58.6 vs 31.4%, el embolismo mayor (60.8 vs 34%, los fenómenos microvasculares (43.4 vs 17.1% y la cirugía valvular (34.7 vs 11.4% ocurrieron significativamente en el Grupo 1 (pPatients with infective endocarditis (IE were studied to assess incidence, clinical features and mortality in a population with either persistent (PF or recurrent fever (RF during treatment. A sample of 81 patients was evaluated. Of these, 46 patients (56.8% had fever during treatment: 35 had PF and 16 had RF (Group 1. This group was compared with 35 patients with IE without fever (Group 2. Age, sex, in-hospital days, nosocomial acquisition, delay in diagnosis, and co-morbidities were similar among each group. The aortic and tricuspid valve compromise, and Staphylococcus aureus as etiologic agent were more frequent in Group 1 (although not significantly. However, the development of complications (95.6 vs. 65.7%, renal dysfunction (58.6 vs. 31.4%, major vessel embolization (60.8 vs. 34%, microvascular phenomena (43.4 vs. 17.1%, infections with MRSA (22.2 vs. 4% and valvular surgery (34.7 vs. 11.4% were significantly higher in Group 1(p<0.05. The most common causes of PF were microvascular phenomena (14

  5. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism...

  6. Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle.

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    Natalie Dow

    Full Text Available Bovine viral diarrhea virus (BVDV, a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution.

  7. Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

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    Zhanyi Li

    2017-01-01

    Full Text Available Background and Objective. The direct-acting antiviral agents (DAAs antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV patients. However, the viral drug resistance-associated variants (RAVs can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88 and D168E in 2.3% isolates (2/88. In NS5A region, we detected Q30R in 93.2% isolates (82/88, L31M in 4.6% isolates (4/88, and H58P in 6.8% isolates (6/88. In NS5B region, we detected A15G in 2.3% isolates (2/88, S96T in 1.1% isolates (1/88, and S282T in 20.7% isolates (17/88 and we detected I482L in 100% isolates (4/4, V494A in 50% isolates (2/4, and V499A in 100% isolates (4/4. Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

  8. Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.

    Science.gov (United States)

    Alidjinou, E K; Engelmann, I; Bossu, J; Villenet, C; Figeac, M; Romond, M-B; Sané, F; Hober, D

    2017-10-03

    Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome. The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR. Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.

  9. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

    2018-04-03

    Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

  10. Factors Predicting HBsAg Seroclearance and Alanine Transaminase Elevation in HBeAg-Negative Hepatitis B Virus-Infected Patients with Persistently Normal Liver Function.

    Directory of Open Access Journals (Sweden)

    Tai-Long Chien

    Full Text Available A certain proportion of hepatitis B virus (HBV-infected patients with persistently normal alanine transaminase (ALT levels have significant fibrosis. Using liver stiffness measurements (Fibroscan® and laboratory data, including serum ALT, quantitative HBsAg (qHBsAg, and HBV DNA, we attempted to predict the natural histories of these patients.Non-cirrhotic HBeAg-negative chronic hepatitis B patients with persistently normal ALT were followed up prospectively with the end points of HBsAg seroclearance and ALT elevation above the upper limit of normal. The factors that were predictive of the end points were identified.A total of 235 patients with an average age of 48.1 +/- 10.7 years were followed up for 7 years. Eight patients (3.4% lost HBsAg, and 15 patients (6.4% experienced ALT elevation. The overall cumulative HBsAg seroclearances were 0.4%, 1.3% and 2.3% at years 1, 3 and 5, respectively. Regarding HBsAg seroclearance, the qHBsAg (< 30 IU/ml cutoff resulted in a hazard ratio (HR of 19.6 with a 95% confidence interval (CI of 2.2-166.7 (P = 0.008. The baseline ALT level (odd ratio (OR 1.075, 95% CI 1.020-1.132, P = 0.006 and a qHBsAg above 1000 IU/ml (3.7, 1.1-12.4, P = 0.032 were associated with ALT elevation. Limited to men, the baseline liver stiffness (1.6, 1.0-2.5, P = 0.031 and a qHBsAg above 1000 IU/ml (10.4, 2.1-52.4, P = 0.004 were factors that were independently associated with ALT elevation.A low qHBsAg level predicted HBsAg clearance. Baseline ALT and a qHBsAg above 1000 IU/ml were independent predictive factors for ALT elevation. Among the men, the independent predictive factors for ALT elevation were qHBsAg and liver stiffness.

  11. Bacterial persistence

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Drug indifference versus persistence. Studies on the mode of ... is a special case of drug indifference, restricted to a small ... to his model (outlined in detail in Lewis 2008), treatment .... belong to the heat and cold shock response family; many.

  12. [Persistent diarrhea

    Science.gov (United States)

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

  13. Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

    Directory of Open Access Journals (Sweden)

    Wesselingh Steven L

    2007-07-01

    Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with nef-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1. Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP as well as long-term nonprogressors (LTNP, longitudinal analysis of nef/long-terminal repeat (LTR sequences demonstrated convergent nef/LTR sequence evolution in SBBC SP and LTNP. Thus, the in vivo pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than nef/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 rev alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36. Results The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus. Conclusion These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated rev alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.

  14. A refratariedade das aves ao "Trypanosoma (Schizotrypanum cruzi" II - refratariedade das galinhas desde o nascimento; persistência da refratariedade após Bursectomia; infecções em ovos embrionados The refractory state of birds toward the Trypanosoma (Schizotrypanum cruzi: II - the refractory state begins at hatching and persists after bursectomy, Infections of embryonnated eggs

    Directory of Open Access Journals (Sweden)

    F. Nery-Guimarães

    1972-01-01

    Full Text Available "A refratariedade das galinhas ao T. (S. cruzi, ocorre desde o nascimento e não é eliminada pela bursectomia hormonal. Noventa e oito pintos de 1 a 15 dias de vida (normais ou tratados com testosterona inoculados com o T. (S. cruzi foram negativos. Deste modo, dificilmente a refratariedade poderia ser interpretada como decorrência de um "anticorpo natural", uma vez que a bursectomia provoca uma queda na produção de anticorpos e das gamaglobulinas. Em cerca de 50% de ovos embrionados (normais ou tratados com o hormônio foram vistos flagelados do 4º ao 12º dia de inoculação, observando-se ninhos de amastigotos em alguns embriões. Os pintos nascidos dos mesmos grupos dos ovos examinados e positivos, foram sistematicamente negativos pelo exame do sangue. Um deles sacrificado horas depois de nascido, mostrou amastigotos no coração, mas esses parasitos pareciam degenerados. Provavelmente, se alguns chegam a evoluir para tripomastigotos, estes são destruídos á medida que as células hospedeiras se rompem, e assim jamais são encontrados no sangue circulante.It has already been shown that the refractory state of chickens toward "T. (S. cruzi" appears early at time of hatch. Fifty-four normal newly hatched and inoculated chicks were negative. it has also been verified that this refractory state persists even after hormonal bursectomy (eggs being injected with 2.5 mg of testosterone. Forty-four bursectomized and inoculated newly hatched chicks were negative. If we consider the fact that bursectomy causes a deficiency in the production of antibodies and gammaglobulins, the refractory state seems not to occur on account of a "natural antibody". Inoculations of "T. (S. cruzi" made in 153 eggs (normal or treated with testosterone produced infections of variable intensity in about 50% of them. Although chicks newly hatched from the same groups were always negative. As we have some embryos to be positive until the 21st day of incubation it seems

  15. Detection of human parvovirus 4 viremia in the follow-up blood samples from seropositive individuals suggests the existence of persistent viral replication or reactivation of latent viral infection.

    Science.gov (United States)

    Chen, Mao-Yuan; Hung, Chien-Ching; Lee, Kuang-Lun

    2015-06-19

    The transmission routes for human parvovirus 4 (PARV4) infections in areas with high seroprevalence are not known. In the work described here, persistent PARV4 viral replication was investigated by conducting a longitudinal study. Ten healthcare workers each provided a blood sample at the beginning of the study (first sample) and 12 months later (second sample). The paired samples were tested for PARV4-positivity by immunoblotting analysis and nested polymerase chain reactions. IgG antibodies against PARV4 were detected in six participants, three of whom also had IgM antibodies against PARV4. The immunoblotting results did not vary over time. PARV4 DNA was detected in the first blood sample from one participant who had IgG antibodies against PARV4 and in the second blood samples from 2 participants who had IgG and IgM antibodies against PARV4. Detection of PARV4 DNA in the second blood samples from two seropositive participants suggests the existence of persistent PARV4 replication or reactivation of inactive virus in the tissues. The finding of persistent or intermittent PARV4 replication in individuals with past infections provides an important clue toward unraveling the non-parenteral transmission routes of PARV4 infection in areas where the virus is endemic.

  16. Persistent angina

    DEFF Research Database (Denmark)

    Jespersen, L.; Abildstrom, S. Z.; Hvelplund, Anders

    2013-01-01

    To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning. We invited 357 patients (men = 191; women = 166; response rate 83......-obstructive CAD or normal coronary arteries than in patients with obstructive CAD. Persistent angina symptoms were associated with long-term anxiety, depression, impaired physical functioning, and QOL irrespective of the degree of CAD. Contrary to common perception, excluding obstructive CAD in stable angina does...... %) with no prior cardiovascular disease who had a first-time coronary angiography (CAG) in 2008-2009 due to suspected stable angina to participate in a questionnaire survey in 2011 with the Seattle Angina Questionnaire and the Hospital Anxiety and Depression Scale as key elements. Long-term persistent angina (i...

  17. Habit persistence

    DEFF Research Database (Denmark)

    Vinther Møller, Stig

    2009-01-01

    This paper uses an iterated GMM approach to estimate and test the consumption based habit persistence model of Campbell and Cochrane (1999) on the US stock market. The empirical evidence shows that the model is able to explain the size premium, but fails to explain the value premium. Further...

  18. Fatal illness associated with pulmonary hypertension in a neonate caused by intrauterine echovirus 11 infection

    NARCIS (Netherlands)

    Willems, A.; Benne, CA; Timmer, A; Bergman, K.A.

    Nonpolio enterovirus (NPEV) infections are known to cause a wide range of illnesses in the neonatal period. In most cases, NPEV is presumed to be contracted during birth. Intrauterine NPEV infections occur infrequently. A case of Intrauterine echovirus 11 infection with pneumonia, persistent

  19. Co-Occurring Disorders

    Science.gov (United States)

    ... the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring Disorders and ... 500 Montgomery Street, Suite 820 Alexandria, VA 22314 Phone (703) 684.7722 Toll Free (800) 969.6642 ...

  20. Experimental infection of Hawai'i 'Amakihi (hemignathus virens) with West Nile virus and competence of a co-occurring vector, culex quinquefasciatus: potential impacts on endemic Hawaiian avifauna.

    Science.gov (United States)

    Lapointe, Dennis; Hofmeister, Erik K.; Atkinson, C.T.; Porter, R.E.; Dusek, Robert J.

    2009-01-01

    Introduced mosquito-borne avian disease is a major limiting factor in the recovery and restoration of native Hawaiian forest birds. Annual epizootics of avian pox (Avipoxvirus) and avian malaria (Plasmodium relictum) likely led to the extinction of some species and continue to impact populations of susceptible Hawaiian honeycreepers (Drepanidinae). The introduction of a novel pathogen, such as West Nile virus (WNV), could result in further population declines and extinctions. During September and October 2004, we infected Hawai'i' Amakihi (Hemignathus virens) with a North American isolate of WNV by needle inoculation and mosquito bite to observe susceptibility, mortality, and illness in this endemic passerine, and to determine the vector competence of the co-occurring, introduced mosquito Culex quinquefasciatus. All experimentally infected Hawai'i ;Amakihi became viremic, with a mean titer >10(5) plaque-forming units (PFU)/ml, and they experienced clinical signs ranging from anorexia and lethargy to ataxia. The fatality rate among needle-inoculated Hawai'i' Amakihi (n=16) was 31.3%, but mortality in free-ranging birds is likely to increase due to predation, starvation, thermal stress, and concomitant infections of avian malaria and pox. Surviving Hawai'i' Amakihi seem to clear WNV from the peripheral blood by 7-10 days postinfection (DPI), and neutralizing antibodies were detected from 9 to 46 DPI. In transmission trials, Hawaiian Cx. quinquefasciatus proved to be a competent vector and Hawai'i Amakihi an adequate amplification host of WNV, suggesting that epizootic WNV could readily become an additional limiting factor of some native Hawaiian bird populations.

  1. Pneumothorax in human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Sibes Kumar Das

    2015-01-01

    Full Text Available Pneumothorax occurs more frequently in people with Human immunodeficiency virus infection in comparison with the general population. In most cases it is secondary the underlying pulmonary disorder, especially pulmonary infections. Though Pneumocystis jiroveci pneumonia is most common pulmonary infection associated with pneumothorax, other infections, non-infective etiology and iatrogenic causes are also encountered. Pneumothorax in these patients are associated with persistent bronchopleural fistula, prolonged hospital stay, poor success with intercostal tube drain, frequent requirement of surgical intervention and increased mortality. Optimal therapeutic approach in these patients is still not well-defined.

  2. Persistent and recurrent hyperparathyroidism.

    Science.gov (United States)

    Guerin, Carole; Paladino, Nunzia Cinzia; Lowery, Aoife; Castinetti, Fréderic; Taieb, David; Sebag, Fréderic

    2017-06-01

    Despite remarkable progress in imaging modalities and surgical management, persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in 2.5-5% of cases of PHPT. The aim of this review is to expose the management of persistent and recurrent hyperparathyroidism. A literature search was performed on MEDLINE using the search terms "recurrent" or "persistent" and "hyperparathyroidism" within the past 10 years. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT. Then, the patient must be evaluated with new imaging modalities. A single adenoma is found in 68% of cases, multiglandular disease in 28%, and parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and graft recurrence. The surgeon must balance the benefits against the risks of a reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If surgery is necessary, a focused approach can be considered in cases of significant imaging foci, but in the case of multiglandular disease, a bilateral neck exploration could be necessary. Patients with multiple endocrine neoplasia syndromes are at high risk of recurrence and should be managed regarding their hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in expert centers is estimated from 93 to 97%. After confirming the diagnosis of PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an expert center with all dedicated competencies.

  3. Infection,

    Science.gov (United States)

    1980-10-16

    characteristic in severe gram-negative sepsis. Hypertriglyceridemia results from an increase in hepatic synthesis in combination with diminished activity of...induced stress, and tissue repair (1). The magnitude and type of nutritional losses caused by an infection reflect both the severity and duration of an... several functional forms of nutrient loss must be anticipated. Functional losses are defined as the within-body losses of nutrients due to infection

  4. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered...

  5. Persistent Modelling

    DEFF Research Database (Denmark)

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered...

  6. HIV Persistence in Adipose Tissue Reservoirs.

    Science.gov (United States)

    Couturier, Jacob; Lewis, Dorothy E

    2018-02-01

    The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

  7. [Formation and persistence of L-variants of Salmonella typhi in experimental typhoid and in carriers].

    Science.gov (United States)

    Levina, G A; Prozorovskiĭ, S V; Iagud, S L; Grumman, M I; Gorelov, A L

    1981-07-01

    The possibility of the induction and persistence of S. typhi L-forms in the process of experimental typhoid infection and carriership has been studied in rabbits. This study has revealed that the process of L-transformation leading to the appearance of the imbalanced growth forms and unstable L-forms of S. typhi in the organism of the animals infected with S. typhi culture may occur under the conditions of carriership. Such changed forms can be detected in the organism of the animals 18 months after the primary infection.

  8. Persistent marine debris

    International Nuclear Information System (INIS)

    Levy, E.M.

    1992-01-01

    In this paper the distribution of persistent marine debris, adrift on world oceans and stranded on beaches globally, is reviewed and related to the known inputs and transport by the major surface currents. Since naturally occurring processes eventually degrade petroleum in the environment, international measures to reduce the inputs have been largely successful in alleviating oil pollution on a global, if not on a local, scale. Many plastics, however, are so resistant to natural degradation that merely controlling inputs will be insufficient, and more drastic and costly measures will be needed to cope with the emerging global problem posed by these materials

  9. New-found fundamentals of bacterial persistence.

    Science.gov (United States)

    Kint, Cyrielle I; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

    2012-12-01

    Persister cells display tolerance to high doses of bactericidal antibiotics and typically comprise a small fraction of a bacterial population. Recently, evidence was provided for a causal link between therapy failure and the presence of persister cells in chronic infections, underscoring the need for research on bacterial persistence. A series of recent breakthroughs have shed light on the multiplicity of persister genes, the contribution of gene expression noise to persister formation, the importance of active responses to antibiotic tolerance and heterogeneity among persister cells. Moreover, the development of in vivo model systems has highlighted the clinical relevance of persistence. This review discusses these recent advances and how this knowledge fundamentally changes the way in which we will perceive the problem of antibiotic tolerance in years to come. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.

    Science.gov (United States)

    Carey, Alison J; Tan, Chee Keong; Mirza, Shaper; Irving-Rodgers, Helen; Webb, Richard I; Lam, Alfred; Ulett, Glen C

    2014-02-15

    Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

  11. Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract.

    Science.gov (United States)

    Tang, Vera A; Rosenthal, Kenneth L

    2010-12-01

    Although the female genital tract is the main portal of entry for sexually transmitted infections in women, we still have limited understanding of the generation, maintenance and characteristics of memory T cells in the local tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and tetramers against the immunodominant HSV glycoprotein B epitope recognized by CD8+ T cells to examine the generation, maintenance and characteristics of anti-HSV memory T cells in the genital tract following acute infection. Our results show that the highest percentage of HSVgB-specific CD8+ T cells was found in the genital tract compared to the spleen or iliac lymphnode. Indeed, although the actual number of CD8+ T cells contracted following viral clearance, approximately one quarter of the CD8+ population that remained in the genital tissue was HSVgB-specific. Memory gB-tetramer+CD8 T cells in the genital tract were positive for CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV-specific CD8 cells were effector memory T cells that lack the capacity for homing to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific populations in the genital tract produced IFNγ when stimulated in vitro and CD4+ cells also produced TNFα. Genital HSVgB-specific memory T cells expressed tissue-homing integrins CD103 (αE integrin) and CD49a (VLA-1 or α1 integrin). Our findings suggest that HSV-specific memory T cells are retained in the genital tract, poised to act as an early line of defense against future virus encounter. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Diagnosis of Persistent Infection in Prosthetic Two-Stage Exchange: Evaluation of the Effect of Sonication on Antibiotic Release from Bone Cement Spacers.

    Science.gov (United States)

    Mariaux, Sandrine; Furustrand Tafin, Ulrika; Borens, Olivier

    2018-01-01

    Introduction : When treating periprosthetic joint infection with a two-stage procedure, antibiotic-impregnated spacers can be used in the interval between prosthetic removal and reimplantation. In our experience, cultures of sonicated spacers are most often negative. The objective of the study was to assess whether that sonication causes an elution of antibiotics, leading to elevated antibiotic concentrations in the sonication fluid inhibiting bacterial growth and thus causing false-negative cultures. Methods : A prospective monocentric study was performed from September 2014 to March 2016. Inclusion criteria were a two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Spacers were made of gentamicin-containing cement to which tobramycin and vancomycin were added. Antibiotic concentrations in the sonication fluid were determined by mass-spectometry (LC-MS). Results : 30 patients were identified (15 hip and 14 knee and 1 ankle arthroplasties). No cases of culture positive sonicated spacer fluid were observed in our serie. In the sonication fluid median concentrations of 13.2µg/ml, 392 µg/ml and 16.6 µg/ml were detected for vancomycin, tobramycin and gentamicin, respectively. According to the European Committee on antimicrobial susceptibility testing (EUCAST), these concentrations released from cement spacer during sonication are higher than the minimal inhibitory concentrations (MICs) for most bacteria relevant in prosthetic joint infections. Conclusion: Spacer sonication cultures remained sterile in all of our cases. Elevated concentrations of antibiotics released during sonication could explain partly negative-cultured sonicated spacers. Indeed, the absence of antibiotic free interval during the two-stages can also contribute to false-negative spacers sonicated cultures.

  13. Persistence of stapedial artery: a case report

    International Nuclear Information System (INIS)

    Carvalho, Bruna Vilaca de; Gaiotti, Juliana Oggioni; Diniz, Renata Lopes Furletti Caldeira; Ribeiro, Marcelo Almeida; Motta, Emilia Guerra Pinto Coelho; Moreira, Wanderval

    2013-01-01

    Persistent stapedial artery is a rare congenital anomaly that occurs by a failure in the involution of such artery. Most patients with persistent stapedial artery are asymptomatic. The imaging diagnosis is made principally by means of multidetector computed tomography. In the present case, persistent stapedial artery was an incidental computed tomography finding. The authors discuss the embryogenesis, computed tomography findings and the importance of an early diagnosis of such anomaly. (author)

  14. Extrahepatic Manifestations of Hepatitis B Virus Infection: Addison’s Disease and Myelofibrosis in a Patient with Persistent Hepatitis B Surface Antigenemia

    Directory of Open Access Journals (Sweden)

    François Somlo

    1993-01-01

    Full Text Available A 60-year-old white male patient was admitted to the hospital with acute abdominal pain, seemingly a self-limited ileus. He was found to be hepatitis B surface antigen (HBsAg-positive. Previous dental treatment was suspected to be the initial source of the infection with hepatitis B virus. Five months later he was re-admitted with a diagnosis of adrenal insufficiency (Addison’s disease which responded well to steroids. Four years later he developed fever and leucocytosis. A bone marrow biopsy revealed myelofibrosis. He had several episodes of pyrexia during his lifetime. After a 12-year period the patient suffered a fatal myocardial infarction. At autopsy the adrenal glands were reduced to scarred remnants and HBsAg was found to be present in the residual adrenocortical cells by immunoflouresence methods. Bone marrow at autopsy revealed myelosclerosis as well HBsAg (via immunofluoresence. Hepatitis B virus was therefore closely correlated with the development of Addison’s disease and myelofibrosis in this case.

  15. Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

    Directory of Open Access Journals (Sweden)

    Angela RI Meyrelles

    2016-02-01

    Full Text Available This study investigated the rate of human papillomavirus (HPV persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample, re-infection (detection of different types of HPV in the 2 samples, and type-specific HPV persistence (the same HPV type found in both samples. An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30% or re-infection (20%. A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79. Our findings show that bonafide (type-specific HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

  16. Sequencing of Escherichia coli that cause persistent and transient Mastitis

    Science.gov (United States)

    The genomes of two strains of Escherichia coli that cause bovine mastitis were sequenced. These strains are known to be associated with persistent and transient mastitis: strain ECA-B causes a transient infection, and ECC-M leads to a persistent infection....

  17. Persistent HPV16/18 infection in Indian women with the A-allele (rs6457617) of HLA-DQB1 and T-allele (rs16944) of IL-1β -511 is associated with development of cervical carcinoma.

    Science.gov (United States)

    Dutta, Sankhadeep; Chakraborty, Chandraditya; Mandal, Ranajit Kumar; Basu, Partha; Biswas, Jaydip; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2015-07-01

    The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β -511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies (N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38), p = 0.03] and CaCx development [OR = 2.03(1.03-5.2), p = 0.02; OR = 2.25(0.96-5.31), p = 0.04] compared with HPV-negative or HPV-cleared normal women. Considering these two loci together, it was evident that the T- and A-alleles rendered significantly increased susceptibility for development of CIN and CaCx compared with HPV-negative and HPV-cleared normal women. Moreover, the T-allele of IL-1β showed increased susceptibility for CIN [OR = 3.62(0.85-17.95), p = 0.04] and CaCx [OR = 2.39(0.91-6.37), p = 0.05] development compared with the HPV-cleared women, even in the presence of the HLA-DQB1 G-allele. Thus, our data suggest that persistent HPV16/18 infection in the cervix due to the presence of the HLA-DQB1 A-allele and chronic inflammation due to the presence of the IL-1β -511 T-allele might predispose women to CaCx development.

  18. Persistence of Salmonid Redds

    Science.gov (United States)

    Buffington, J. M.; Buxton, T.; Fremier, A. K.; Hassan, M. A.; Yager, E.

    2013-12-01

    incubation relative to high flows); and population size (density of redds and extent of streambed alteration within a given reach). Species and life history also control the location of spawning within the basin, dictating the flow and sediment supply regimes. A theoretical framework is developed for predicting redd persistence as a function of the above physical and biological factors. We expect that long-lived redds will indicate either that the river is not competent to re-work the effects of spawning or that spawning occurs after peak flow events that are capable of modifying redd features. The longevity of redds and their associated effects on fluvial processes also provides a measure of the degree of potential ecological conditioning for future generations of fish. Future work will test the framework in field and laboratory settings.

  19. Persistence of Leishmania antigen in C57Bl/6j inbred mice infected with Leishmania (Leishmania amazonensis Persistência do antígeno da Leishmania no camundongo isogênico C57Bl/6j infectado com a Leishmania (Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    C. Vasconcellos

    1999-07-01

    Full Text Available PURPOSE. To develop an animal model for studying mucocutaneous leishmaniasis. METHODS. The hind footpad of C57Bl/6j inbred mice was experimentally infected with 10(7 Leishmania (Leishmania amazonensis promastigote and the skin was studied through light and electron transmission microscopy and immunohistochemistry (PAP techniques. RESULTS. There were morphological evidences of cellular immune mechanisms and hypersensitivity reaction after eight weeks of infection and metastasis and well shaped parasites at ultrastructural level by fifty-one weeks post infection. Relapse of infection with mucosa lesions occurred around the 50th week after inoculation. CONCLUSION. The use of this animal model in long term follow up could be an useful experimental model for human mucocutaneous leishmaniasis.OBJETIVO. Desenvolver um modelo experimental para o estudo da leishmaniose cutâneo-mucosa. MÉTODOS. O coxim plantar traseiro de camundongos isogênicos C57Bl/6j foi inoculado com 10(7 formas promastigotas da Leishmania (Leishmania amazonensis e a pele foi estudada através da microscopia óptica e eletrônica e de técnica imunohistoquímica (PAP. RESULTADOS. Ocorreram evidências morfológicas de mecanismos imunes mediados por células, concomitantemente ao de reação de hipersensibilidade, após a oitava semana de infecção e a presença de parasitas com ultraestrutura preservada na quinquagésima primeira semana após a infecção. Houve recidiva da infecção com surgimento de lesões mucosas por volta da 50a semana pós inoculação. CONCLUSÃO. Este modelo animal, com um período de tempo de seguimento prolongado, poderia ser empregado como modelo para o estudo experimental da leishmaniose cutâneo-mucosa.

  20. Efficacy of standard therapies against Ureaplasma species and persistence among men with non-gonococcal urethritis enrolled in a randomized controlled trial

    Science.gov (United States)

    Khosropour, Christine M.; Manhart, Lisa E.; Gillespie, Catherine W.; Lowens, M. Sylvan; Golden, Matthew R.; Jensen, Nicole L.; Kenny, George E.; Totten, Patricia A.

    2015-01-01

    Objective U. urealyticum biovar 2 (UU-2) but not U. parvum (UP) has been associated with non-gonococcal urethritis (NGU), but little is known about species-specific responses to standard therapies. We examined species-specific treatment outcomes and followed men with treatment failure for 9 weeks. Methods From May 2007-July 2011, men aged ≥16 attending an STD clinic in Seattle, Washington with NGU (urethral discharge or urethral symptoms plus ≥5 PMNs/HPF) were enrolled in a double-blind, randomized trial. Participants received active azithromycin (1g) + placebo doxycycline or active doxycycline (100mg bid × 7d) + placebo azithromycin. Ureaplasmas were detected in culture followed by species-specific PCR. Outcomes were assessed at 3, 6, and 9 weeks. At 3 weeks, men with persistent Ureaplasmas received “reverse therapy” (e.g., active doxycycline if they first received active azithromycin). At 6 weeks, persistently-positive men received moxifloxacin (400mg × 7d). Results Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP, respectively, and returned at 3 weeks. Persistent infection was similar for UU-2-infected men initially treated with azithromycin or doxycycline (25% vs. 31%, P=0.53), but differed somewhat for men with UP (45% vs. 24%; P=0.11). At 6 weeks, 57% of UU-2-infected and 63% of UP-infected men who received both drugs had persistent infection. Failure after moxifloxacin occurred in 30% and 36%, respectively. Persistent detection of UU-2 or UP was not associated with signs/symptoms of NGU. Conclusion Persistent infection after treatment with doxycycline, azithromycin, and moxifloxacin was common for UU and UP, but not associated with persistent urethritis. PMID:25616607

  1. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-01-01

    persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc

  2. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  3. Persistence of Mycoplasma genitalium following azithromycin therapy.

    Directory of Open Access Journals (Sweden)

    Catriona S Bradshaw

    Full Text Available BACKGROUND: To determine clinical outcomes and cure rates for M.genitalium genital infection in men and women following azithromycin 1 g. METHODOLOGY: Patients attending Melbourne Sexual Health Centre between March 2005 and November 2007 with urethritis/epididymitis, cervicitis/pelvic inflammatory disease and sexual contacts of M.genitalium were tested for M.genitalium by polymerase chain reaction (PCR. M.genitalium-infection was treated with 1 g of azithromycin and a test-of-cure (toc was performed one month post-azithromycin. Response to azithromycin, and response to moxifloxacin (400 mg daily for 10 days in individuals with persistent infection post-azithromycin, was determined. PRINCIPAL FINDINGS: Of 1538 males and 313 females tested, 161 males (11% and 30 females (10% were infected with M.genitalium. A toc was available on 131 (69% infected individuals (median = 36 days [range 12-373]. Of 120 individuals prescribed azithromycin only pre-toc, M.genitalium was eradicated in 101 (84%, 95% confidence intervals [CI]: 77-90% and persisted in 19 (16%, 95% CI: 10-23%. Eleven individuals with persistent infection (9%, 95% CI: 5-15% had no risk of reinfection from untreated-partners, while eight (7%, 95% CI: 3-12% may have been at risk of reinfection from doxycycline-treated or untreated-partners. Moxifloxacin was effective in eradicating persistent infection in all cases not responding to azithromycin. Patients with persistent-M.genitalium were more likely to experience persistent symptoms (91%, compared to patients in whom M.genitalium was eradicated (17%, p<0.0001. CONCLUSION: Use of azithromycin 1 g in M.genitalium-infected patients was associated with unacceptable rates of persistent infection, which was eradicated with moxifloxacin. These findings highlight the importance of follow-up in M.genitalium-infected patients prescribed azithromycin, and the need to monitor for the development of resistance. Research to determine optimal first and

  4. Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters

    Directory of Open Access Journals (Sweden)

    Elizabeth L. Sandvik

    2015-11-01

    Full Text Available Staphylococcus aureus is a notorious pathogen with a propensity to cause chronic, non-healing wounds. Bacterial persisters have been implicated in the recalcitrance of S. aureus infections, and this motivated us to examine the persistence of S. aureus to ciprofloxacin, a quinolone antibiotic. Upon treatment of exponential phase S. aureus with ciprofloxacin, we observed that survival was a non-monotonic function of ciprofloxacin concentration. Maximal killing occurred at 1 µg/mL ciprofloxacin, which corresponded to survival that was up to ~40-fold lower than that obtained with concentrations ≥ 5 µg/mL. Investigation of this phenomenon revealed that the non-monotonic response was associated with prophage induction, which facilitated killing of S. aureus persisters. Elimination of prophage induction with tetracycline was found to prevent cell lysis and persister killing. We anticipate that these findings may be useful for the design of quinolone treatments.

  5. HPV Infections in Adolescents

    Directory of Open Access Journals (Sweden)

    Anna-Barbara Moscicki

    2007-01-01

    Full Text Available Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50–80% having infections within 2–3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS and low grade (LSIL. The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation.

  6. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  7. Phage T4 SegB protein is a homing endonuclease required for the preferred inheritance of T4 tRNA gene region occurring in co-infection with a related phage.

    Science.gov (United States)

    Brok-Volchanskaya, Vera S; Kadyrov, Farid A; Sivogrivov, Dmitry E; Kolosov, Peter M; Sokolov, Andrey S; Shlyapnikov, Michael G; Kryukov, Valentine M; Granovsky, Igor E

    2008-04-01

    Homing endonucleases initiate nonreciprocal transfer of DNA segments containing their own genes and the flanking sequences by cleaving the recipient DNA. Bacteriophage T4 segB gene, which is located in a cluster of tRNA genes, encodes a protein of unknown function, homologous to homing endonucleases of the GIY-YIG family. We demonstrate that SegB protein is a site-specific endonuclease, which produces mostly 3' 2-nt protruding ends at its DNA cleavage site. Analysis of SegB cleavage sites suggests that SegB recognizes a 27-bp sequence. It contains 11-bp conserved sequence, which corresponds to a conserved motif of tRNA TpsiC stem-loop, whereas the remainder of the recognition site is rather degenerate. T4-related phages T2L, RB1 and RB3 contain tRNA gene regions that are homologous to that of phage T4 but lack segB gene and several tRNA genes. In co-infections of phages T4 and T2L, segB gene is inherited with nearly 100% of efficiency. The preferred inheritance depends absolutely on the segB gene integrity and is accompanied by the loss of the T2L tRNA gene region markers. We suggest that SegB is a homing endonuclease that functions to ensure spreading of its own gene and the surrounding tRNA genes among T4-related phages.

  8. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

    Science.gov (United States)

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

  9. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

    Directory of Open Access Journals (Sweden)

    Lisbeth Ramirez-Carvajal

    Full Text Available Foot-and-mouth disease (FMD is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

  10. Evaluation of economic effects and the health and performance of the general cattle population after exposure to cattle persistently infected with bovine viral diarrhea virus in a starter feedlot.

    Science.gov (United States)

    Hessman, Bill E; Fulton, Robert W; Sjeklocha, David B; Murphy, Timothy A; Ridpath, Julia F; Payton, Mark E

    2009-01-01

    To evaluate economic effects and health and performance of the general cattle population after exposure to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) in a feedlot. 21,743 high-risk calves from the southeastern United States. PI status was determined by use of an antigen-capture ELISA (ACE) and confirmed by use of a second ACE, reverse transcriptase-PCR assay of sera, immunohistochemical analysis, and virus isolation from sera. Groups with various amounts of exposure to BVDV PI cattle were used. After being placed in the feedlot, identified PI cattle were removed from 1 section, but PI cattle remained in another section of the feedlot. Exposure groups for cattle lots arriving without PI animals were determined by spatial association to cattle lots, with PI animals remaining or removed from the lot. 15,348 cattle maintained their exposure group. Performance outcomes improved slightly among the 5 exposure groups as the risk for exposure to BVDV PI cattle decreased. Health outcomes had an association with exposure risk that depended on the exposure group. Comparing cattle lots with direct exposure with those without direct exposure revealed significant improvements in all performance outcomes and in first relapse percentage and mortality percentage in the health outcomes. Economic analysis revealed that fatalities accounted for losses of $5.26/animal and performance losses were $88.26/animal. This study provided evidence that exposure of the general population of feedlot cattle to BVDV PI animals resulted in substantial costs attributable to negative effects on performance and increased fatalities.

  11. Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations

    Directory of Open Access Journals (Sweden)

    Hardstaff Joanne L

    2012-06-01

    Full Text Available Abstract Background The persistence of bovine TB (bTB in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles. The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model. Results The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6–8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone. Conclusions External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to

  12. Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations.

    Science.gov (United States)

    Hardstaff, Joanne L; Bulling, Mark T; Marion, Glenn; Hutchings, Michael R; White, Piran C L

    2012-06-27

    The persistence of bovine TB (bTB) in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles). The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model. The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6-8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone. External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to reduce bTB in badgers include efforts to minimise such

  13. Rarity and persistence.

    Science.gov (United States)

    Vermeij, Geerat J; Grosberg, Richard K

    2018-01-01

    Rarity is a population characteristic that is usually associated with a high risk of extinction. We argue here, however, that chronically rare species (those with low population densities over many generations across their entire ranges) may have individual-level traits that make populations more resistant to extinction. The major obstacle to persistence at low density is successful fertilisation (union between egg and sperm), and chronically rare species are more likely to survive when (1) fertilisation occurs inside or close to an adult, (2) mate choice involves long-distance signals, (3) adults or their surrogate gamete dispersers are highly mobile, or (4) the two sexes are combined in a single individual. In contrast, external fertilisation and wind- or water-driven passive dispersal of gametes, or sluggish or sedentary adult life habits in the absence of gamete vectors, appear to be incompatible with sustained rarity. We suggest that the documented increase in frequency of these traits among marine genera over geological time could explain observed secular decreases in rates of background extinction. Unanswered questions remain about how common chronic rarity actually is, which traits are consistently associated with chronic rarity, and how chronically rare species are distributed among taxa, and among the world's ecosystems and regions. © 2017 John Wiley & Sons Ltd/CNRS.

  14. A role for the non-canonical Wnt-ß-Catenin and TGF-ß signaling pathways in the induction of tolerance during the establishment of a Salmonella enterica serovar Enteritidis persistent cecal infection in chickens

    Science.gov (United States)

    Non-typhoidal Salmonella enterica induce an early pro-inflammatory response in chickens. However, the response is short-lived, asymptomatic of disease, resulting in a persistent colonization of the ceca, and fecal shedding of bacteria. The underlying mechanisms that control this persistent infecti...

  15. MYCOPLASMA INFECTION IN CHILDREN: CURRENT DIAGNOSIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    F. S. Harlamova

    2016-01-01

    Full Text Available Presents literary and own data (52 patients on the role of mycoplasma infection. Mycoplasma infection is associated with long-term antigenemia in children, causes recurrent disease and autoimmunity. Among the 52 examined patients diagnosed with pneumonia in 17, bronchitis — from 19, rhinosinusitis  — at 11, StevensJohnson syndrome — in 2 children.  In half the cases mycoplasmosis occurs against the backdrop of persistent active herpes virus infection (in 27 children (52%. To optimize the causal and pathogenetic therapy mycoplasma requires correction of immune disorders.

  16. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  17. Oxidation mechanisms occurring in wines

    OpenAIRE

    Oliveira, Carla Maria; Ferreira, António César Silva; Freitas, Victor De; Silva, Artur M. S.

    2011-01-01

    The present review aims to show the state of the art on the oxidation mechanisms occurring in wines, as well as the methods to monitor, classify and diagnose wine oxidation. Wine oxidation can be divided in enzymatic oxidation and non-enzymatic oxidation. Enzymatic oxidation almost entirely occurs in grape must and is largely correlated with the content of hydroxycinnamates, such as caffeoyltartaric acid and paracoumaroyltartaric acid, and flavan-3-ols. Non-enzymatic oxidation, al...

  18. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Eligio Pizzigallo

    2010-08-01

    excluded from these forms and mantain their nosographic (e.g. T or B cell or NK type lymphomas and pathogenetic collocation, even when they occur within chronic forms of EBV infection. In the pathogenesis, near to the programs of latency of the virus, the genetic and environmental factors, independent from the real natural history of EBV infection, play a crucial role. Finally, it was realized a review of cases - not much numerous in literature – of chronic EBV infection associated to chronic liver and neurological diseases, where the modern techniques of molecular biology should be useful to obtain a more exact etiologic definition, not always possibile to reach in the past. The wide variety of clinical forms associated to the EBV chronic infection makes difficult the finding of a univocal pathogenetic link. There is no doubt, however, that a careful examination of the different clinical forms described in this review should be useful to open new horizons to the study of the persistent viral infections and the still not well cleared pathologies that they can induce in the human host.

  19. Role of the chronic bacterial infection in urinary bladder carcinogenesis

    International Nuclear Information System (INIS)

    Higgy, N.A.

    1985-01-01

    The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3 H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection. 3 H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis

  20. Pair formation models for sexually transmitted infections: A primer

    Directory of Open Access Journals (Sweden)

    Mirjam Kretzschmar

    2017-08-01

    Full Text Available For modelling sexually transmitted infections, duration of partnerships can strongly influence the transmission dynamics of the infection. If partnerships are monogamous, pairs of susceptible individuals are protected from becoming infected, while pairs of infected individuals delay onward transmission of the infection as long as they persist. In addition, for curable infections re-infection from an infected partner may occur. Furthermore, interventions based on contact tracing rely on the possibility of identifying and treating partners of infected individuals. To reflect these features in a mathematical model, pair formation models were introduced to mathematical epidemiology in the 1980's. They have since been developed into a widely used tool in modelling sexually transmitted infections and the impact of interventions. Here we give a basic introduction to the concepts of pair formation models for a susceptible-infected-susceptible (SIS epidemic. We review some results and applications of pair formation models mainly in the context of chlamydia infection. Keywords: Pair formation, Mathematical model, Partnership duration, Sexually transmitted infections, Basic reproduction number

  1. Persistent myalgia following whiplash.

    Science.gov (United States)

    Dommerholt, Jan

    2005-10-01

    Persistent myalgia following whiplash is commonly considered the result of poor psychosocial status, illness behavior, or failing coping skills. However, there is much evidence that persistent myalgia may be due to neurophysiologic mechanisms involving peripheral and central sensitization. Myofascial trigger points may play a crucial role in maintaining sensitization. Recent research suggests that the chemical environment of myofascial trigger points is an important factor. Several consequences are reviewed when central pain mechanisms and myofascial trigger points are included in the differential diagnosis and in the management of patients with persistent pain following whiplash.

  2. Introduction: Persistent Modelling

    DEFF Research Database (Denmark)

    Ayres, Phil

    2012-01-01

    This introduction to 'Persistent Modelling – an extended role for architectural representation' identifies how the book probes the relationship between representation and the represented, in an architectural context. It discusses how the book presents an examination and discussion of historical......, familiar contemporary and, perhaps, not so familiar emerging manifestations of this relation. What persists from this probing, fully intact, is that representation and the represented remain inextricably related in our contemporary and emerging practices. What comes into focus is that the nature...

  3. Naturally Occurring Radioactive Materials (NORM)

    International Nuclear Information System (INIS)

    Gray, P.

    1997-01-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training)

  4. Naturally Occurring Radioactive Materials (NORM)

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  5. Naturally occurring radionuclides in food

    International Nuclear Information System (INIS)

    Djujic, I.

    1995-01-01

    The naturally occurring radionuclides are the major source of radiation exposure to humans. The principal way of natural radiation exposure is the inhalation of 222 Rn decay products (about 85% of the total). The remainder is equally divided between internally deposited radionuclides, cosmic and terrestrial sources. In the present study, the content of 40 K, 210 Pb, 226 Ra, 230 Th, 232 Th and 238 U in representative food samples (milk, pork, beef, potatoes, wheat and corn flour) and samples of different food items that do not represent entire national production but provide interesting additional data for approximative calculation of naturally occurring radionuclide intake is presented. Daily weight of food eaten, participation of food groups, as well as daily intake by food of mentioned naturally occurring radionuclides in the Serbian diet was obtained on the base of house hold budget surveys. The result obtained for daily intake estimates in mBq for Serbian population are 78.1 ( 40 K), 38.2( 210 Pb), 52.3( 226 Ra), 2.0( 230 Th) and 12.5( 238 U). (author)

  6. Early occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.

    1985-01-01

    This chapter deals with health-risk estimates for early and continuing effects of exposure to ionizing radiations that could be associated with light water nuclear power plants accidents. Early and continuing effects considered are nonneoplastic diseases and symptoms that normally occur soon after radiation exposure, but may also occur after years have passed. They are generally associated with relatively high (greater than 1 Gy) doses. For most of the effects considered, there is a practical dose threshold. Organs of primary interest, because of their high sensitivity or the likelihood of receiving a large radiation dose, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. In utero exposure of the fetus is also considered. New data and modeling techniques available since publication of the Reactor Safety Study (WASH 1400, 1975) were used along with data cited in the Study to develop improved health-risk models for morbidity and mortality. The new models are applicable to a broader range of accident scenarios, provide a more detailed treatment of dose protraction effects, and include morbidity effects not considered in the Reactor Safety Study. 115 references, 20 figures, 19 tables

  7. Naturally-occurring alpha activity

    Energy Technology Data Exchange (ETDEWEB)

    Mayneord, W V

    1960-12-01

    In view of the difficulties of assessing the significance of man-made radioactivity it is important to study for comparison the background of natural radioactivity against which the human race has evolved and lives. It is also important to define the present levels of activity so that it will be possible to detect and study as quickly as possible any changes which may occur owing to the release into the environment of new radioactive materials. Moreover, by the study of the behaviour of natural radioactivity light may be shed upon that of the artificially produced isotopes and a number of analogies traced between the two groups. These concepts have led to studies of naturally-occurring radioactive materials alongside a programme of research into fission products in food, water and air, as well as studies of the metabolism of both sets of materials in the human body. Since the last report there has been a useful increase in our knowledge of natural radioactivity in the biosphere, and its levels relative to the new man-made activities. These studies have necessitated technical developments, particularly in the methods of measuring and identifying alpha-ray emitters, to which group many of the more important natural radioactive materials belong.

  8. Forecasting autoregressive time series under changing persistence

    DEFF Research Database (Denmark)

    Kruse, Robinson

    Changing persistence in time series models means that a structural change from nonstationarity to stationarity or vice versa occurs over time. Such a change has important implications for forecasting, as negligence may lead to inaccurate model predictions. This paper derives generally applicable...

  9. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  10. Persistent luminescence nanothermometers

    Science.gov (United States)

    Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

    2017-08-01

    Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

  11. Naturally occurring methyl salicylate glycosides.

    Science.gov (United States)

    Mao, Ping; Liu, Zizhen; Xie, Meng; Jiang, Rui; Liu, Weirui; Wang, Xiaohong; Meng, Shen; She, Gaimei

    2014-01-01

    As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed from natural substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities, anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates' without resulting in serious side effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could contribute to the new drug discovery.

  12. Chikungunya Arthritis Mechanisms in the Americas (CAMA): A cross sectional analysis of chikungunya arthritis patients 22 months post-infection demonstrates a lack of viral persistence in synovial fluid

    Science.gov (United States)

    2017-06-30

    2010;120(3): 894-906. 442 (8) Hoarau JJ , Jaffar Bandjee MC, Krejbich Trotot P, Das T, Li-Pat-Yuen G, Dassa B, et al. Persistent chronic 443...Fingolimod treatment abrogates 478 chikungunya virus-induced arthralgia. Sci Transl Med. 2017;9(375): eaal1333. 479 (24) Miner JJ , Cook LE, Hong

  13. Host phylogeny determines viral persistence and replication in novel hosts.

    Directory of Open Access Journals (Sweden)

    Ben Longdon

    2011-09-01

    Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  14. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  15. What occurred in the reactors

    International Nuclear Information System (INIS)

    Kudo, Kazuhiko

    2013-01-01

    Described is what occurred in the reactors of Fukushima Daiichi Nuclear Power Plant at the Tohoku earthquake and tsunami (Mar. 11, 2011) from the aspect of engineering science. The tsunami attacked the Plant 1 hr after the quake. The Plant had reactors in buildings no.1-4 at 10 m height from the normal sea level which was flooded by 1.5-5.5 m high wave. All reactors in no.1-6 in the Plant were the boiling water type, and their core nuclear reactions were stopped within 3 sec due to the first quake by control rods inserted automatically. Reactors in no.1-5 lost their external AC power sources by the breakdown and subsequent submergence (no.1-4) of various equipments and in no.1, 2 and 4, the secondary DC power was then lost by the battery death. Although the isolation condenser started to cool the reactor in no.1 after DC cut, its valve was then kept closed to heat up the reactor, leading to the reaction of heated Zr in the fuel tube and water to yield H 2 which was accumulated in the building: the cause of hydrogen explosion on 12th. The reactor in no.2 had the reactor core isolation cooling system (RCIC) which operated normally for few hrs, then probably stopped to heat up the reactor, resulting in meltdown of the core but no explosion occurred because of the opened door of the blowout panel on the wall by the blast of no.1 explosion. The reactor in no.3 had RCIC and high pressure coolant injection system, but their works stopped to result in the core damage and H 2 accumulation leading to the explosion on 14th. The reactor in no.4 had not been operated because of its periodical annual examination, but was explored on 15th, of which cause was thought to be due to backward flow of H 2 from no.3. Finally, the author discusses about this accident from the industrial aspect of the design of safety level (defense in depth) on international views, and problems and tasks given. (T.T.)

  16. Earl occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.

    1989-01-01

    This chapter develops health-risk models for early and continuing effects of exposure to beta or gamma radiation that could be associated with light water nuclear power plant accidents. The main purpose of the chapter is to provide details on each health-risk model and on the data used. Early and continuing effects considered are prodromal symptoms and nonneoplastic diseases that usually occur soon after a brief radiation exposure. These effects are generally associated with relatively high (greater than 1 Gy) absorbed organ doses. For most of the effects considered, there is an absorbed organ dose threshold below which no effects are seen. Some information is provided on health effects observed in victims of the Chernobyl power plant accident. Organs of primary interest, because of their high sensitivity or their potential for receiving large doses, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. Exposure of the fetus is also considered. Additional data and modeling techniques available since publication of the Reactor Safety Study were used to obtain models for morbidity and mortality

  17. Does overtraining occur in triathletes?

    Directory of Open Access Journals (Sweden)

    I Margaritis

    2003-06-01

    Full Text Available 1. Objective: Long distance triathlon training is characterized by considerably high volume training loads. This volume can provoke an overtraining state. The aim of the study was to determine whether overtraining occurs in well-trained male triathletes in relation with their volume training loads. 2. Experimental design: A questionnaire investigation was completed two days before the Nice long-distance triathlon (October 1995: 4-km swim, 120-km bike ride and 30-km run. 3. Participants: Ninety-three well-trained male triathletes who took part in the triathlon race. 4. Measures: A questionnaire to relate clinical symptoms, which are known to appear in case of overtraining, was collected. 5. Results: 39.8% of the questioned triathletes reported a decrease in triathlon performances within the last month preceding the race. Moreover, these triathletes exhibited significantly more overtraining-relied symptoms than the others (5.9±3.8 vs 3.4±2.6, P<0.05. Surprisingly, the occurrence of overtraining in triathletes appears not to depend on the volume training loads. 6. Conclusions: These results suggest that overtraining has to be considered in the case of triathletes. This preliminary study evidences the need for further investigation in order to monitor triathletes training respond and prevent overtraining.

  18. Persistent genital arousal disorder

    DEFF Research Database (Denmark)

    Eibye, Simone; Jensen, Hans Mørch

    2014-01-01

    We report a case of a woman suffering from persistent genital arousal disorder (PGAD) after paroxetine cessation. She was admitted to a psychiatric department and diagnosed with agitated depression. Physical investigation showed no gynaecological or neurological explanation; however, a pelvic MRI...

  19. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Wild caught fish, especially marine fish, can contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. This led to a ban in 2011 on eel fishing due to health concerns. Many of the marine POPs have been related to

  20. Contributions to Persistence Theory

    Directory of Open Access Journals (Sweden)

    Du Dong

    2014-12-01

    Full Text Available Persistence theory discussed in this paper is an application of algebraic topology (Morse Theory [29] to Data Analysis, precisely to qualitative understanding of point cloud data, or PCD for short. PCD can be geometrized as a filtration of simplicial complexes (Vietoris-Rips complex [25] [36] and the homology changes of these complexes provide qualitative information about the data. Bar codes describe the changes in homology with coefficients in a fixed field. When the coefficient field is ℤ2, the calculation of bar codes is done by ELZ algorithm (named after H. Edelsbrunner, D. Letscher, and A. Zomorodian [20]. When the coefficient field is ℝ, we propose an algorithm based on the Hodge decomposition [17]. With Dan Burghelea and Tamal K. Dey we developed a persistence theory which involves level sets discussed in Section 4. We introduce and discuss new computable invariants, the “relevant level persistence numbers” and the “positive and negative bar codes”, and explain how they are related to the bar codes for level persistence. We provide enhancements and modifications of ELZ algorithm to calculate such invariants and illustrate them by examples.

  1. Is corruption really persistent?

    NARCIS (Netherlands)

    Seldadyo, H.; de Haan, J.

    Theoretical and empirical research on corruption generally concludes that corruption is persistent. However, using International Country Risk Guide data for the period 1984-2008 for 101 countries, we find strong evidence that corruption changes over time. In the present study, corruption levels of

  2. [Persistence of Pseudomonas aeruginosa strains in patients of Federal Scientific Center of Transplantology and Artificial Organs].

    Science.gov (United States)

    Avetisian, L R; Voronina, O L; Chernukha, M Iu; Kunda, M S; Gabrielian, N I; Lunin, V G; Shaginian, I A

    2012-01-01

    Study genetic diversity of P. aeruginosa strains persisting in patients of Federal Scientific Center of Transplantology and Artificial Organs, and main factors facilitating persistence of strains in the hospital. 136 P. aeruginosa strains isolated from patients of the center for 3 years 6 months were genotyped by RAPD-PCR and MLST methods and studied for antibiotics resistance and presence of integrons. Genetic diversity of strains persisting in hospital was established. Strains of main genotypes ST235, ST446, ST598 were isolated from patients of various surgical departments. Patients were shown to be colonized by these strains during stay in reanimation and intensive therapy department (RITD) of the hospital. Strains of dominant genotype 235 were isolated from 47% of examined patients during more than 3 years. Only genotype 235 strains contained integron with cassettes of antibiotics resistance genes blaGES5 and aadA6 in the genome. The data obtained show that over the period of observation in the center 1 clone of P. aeruginosa that belonged to genotype 235 dominated. This clone was endemic for this hospital and in the process of prolonged persistence became more resistant to antibiotics. Colonization of patients with these strains occurs in RITD. This confirms the necessity of constant monitoring of hospital microflora for advance detection of potentially dangerous epidemic hospital strains able to cause hospital infections.

  3. Changes in persistence, spurious regressions and the Fisher hypothesis

    DEFF Research Database (Denmark)

    Kruse, Robinson; Ventosa-Santaulària, Daniel; Noriega, Antonio E.

    Declining inflation persistence has been documented in numerous studies. When such series are analyzed in a regression framework in conjunction with other persistent time series, spurious regressions are likely to occur. We propose to use the coefficient of determination R2 as a test statistic to...

  4. What Makes Pseudomonas Aeruginosa Persist in the Lungs of CF Patients?

    DEFF Research Database (Denmark)

    Johansen, H.; Madsen Sommer, Lea Mette; Marvig, Rasmus Lykke

    2015-01-01

    The most important problem for cystic fibrosis (CF) patients is the airway infections responsible for the gradually decreasing lung function as the infections persist. We have investigated properties that may be involved in persistence of P. aeruginosa (PA) in the lungs of young CF children by co...

  5. Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

    Science.gov (United States)

    Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

    2017-06-01

    Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

  6. APPLICATION OF THE NATURALLY-OCCURRING DEUTERIUM ISOTOPE TO TRACING THE CAPILLARY FRINGE

    Science.gov (United States)

    Naturally-occurring deuterium is a useful tracer of subsurface hydrologic processes. A possible application includes the identification of capillary fringes in the vadose zone. Multiple and discontinuous water tables persist in many temperate regions, under various hydrogeologi...

  7. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  8. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  9. Methicillin-resistant Staphylococcus aureus infection and hospitalization in high-risk patients in the year following detection.

    Directory of Open Access Journals (Sweden)

    Susan S Huang

    Full Text Available Many studies have evaluated methicillin-resistant Staphylococcus aureus (MRSA infections during single hospitalizations and subsequent readmissions to the same institution. None have assessed the comprehensive burden of MRSA infection in the period after hospital discharge while accounting for healthcare utilization across institutions.We conducted a retrospective cohort study of adult patients insured by Harvard Pilgrim Health Care who were newly-detected to harbor MRSA between January 1991 and December 2003 at a tertiary care medical center. We evaluated all MRSA-attributable infections associated with hospitalization in the year following new detection, regardless of hospital location. Data were collected on comorbidities, healthcare utilization, mortality and MRSA outcomes. Of 591 newly-detected MRSA carriers, 23% were colonized and 77% were infected upon detection. In the year following detection, 196 (33% patients developed 317 discrete and unrelated MRSA infections. The most common infections were pneumonia (34%, soft tissue (27%, and primary bloodstream (18% infections. Infections occurred a median of 56 days post-detection. Of all infections, 26% involved bacteremia, and 17% caused MRSA-attributable death. During the admission where MRSA was newly-detected, 14% (82/576 developed subsequent infection. Of those surviving to discharge, 24% (114/482 developed post-discharge infections in the year following detection. Half (99/185, 54% of post-discharge infections caused readmission, and most (104/185, 55% occurred over 90 days post-discharge.In high-risk tertiary care patients, newly-detected MRSA carriage confers large risks of infection and substantial attributable mortality in the year following acquisition. Most infections occur post-discharge, and 18% of infections associated with readmission occurred in hospitals other than the one where MRSA was newly-detected. Despite gains in reducing MRSA infections during hospitalization, the

  10. Persistent Model #2

    DEFF Research Database (Denmark)

    2013-01-01

    Tensegrity structures and Inflatable membranes can be considered analogous. They can both be described as pressure based systems in which a coherent envelope is tensioned through compressive force in order to achieve a state of self-equilibrium. Persistent Model #2 is a full-scale speculative pro...... Modelling and a sustained critical investigation of the roles digital tools can play in extending the ways in which we think, design, realise and experience architecture....

  11. Intergenerational Top Income Persistence

    DEFF Research Database (Denmark)

    Munk, Martin D.; Bonke, Jens; Hussain, M. Azhar

    2016-01-01

    In this paper, we investigate intergenerational top earnings and top income mobility in Denmark. Access to administrative registers allowed us to look at very small fractions of the population. We find that intergenerational mobility is lower in the top when including capital income in the income...... measure— for the rich top 0.1% fathers and sons the elasticity is 0.466. Compared with Sweden, however, the intergenerational top income persistence is about half the size in Denmark....

  12. Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.

    Science.gov (United States)

    Phipps, Warren; Saracino, Misty; Magaret, Amalia; Selke, Stacy; Remington, Mike; Huang, Meei-Li; Warren, Terri; Casper, Corey; Corey, Lawrence; Wald, Anna

    2011-01-15

    Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking. For this study, 377 healthy adults with history of symptomatic genital HSV-2 infection collected anogenital swabs for HSV-2 DNA polymerase chain reaction for at least 30 consecutive days. Time since first genital herpes episode was significantly associated with reduced genital shedding. Total HSV shedding occurred on 33.6% of days in participants <1 year, 20.6% in those 1-9 years, and 16.7% in those ≥10 years from first episode. Subclinical HSV shedding occurred on 26.2% of days among participants <1 year, 13.1% in those 1-9 years, and 9.3% in those ≥10 years from first episode. On days with HSV detection, mean quantity was 4.9 log₁₀ copies/mL for those <1 year, 4.7 log₁₀ copies/mL among those 1-9 years, and 4.6 log₁₀ copies/mL among those ≥10 years since first episode. Rates of total and subclinical HSV-2 shedding decrease after the first year following the initial clinical episode. However, viral shedding persists at high rates and copy numbers years after infection, and therefore may pose continued risk of HSV-2 transmission to sexual partners.

  13. Numeric invariants from multidimensional persistence

    Energy Technology Data Exchange (ETDEWEB)

    Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

  14. Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population

    Directory of Open Access Journals (Sweden)

    McIntyre James A

    2008-07-01

    Full Text Available Abstract Background In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN, the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ. Methods Women with high grade squamous intraepithelial lesions or worse (HSIL, less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression Results The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear. Conclusion We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.

  15. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Delia Racciatti

    2010-02-01

    clinical expression of a first group of chronic EBV infections characterized by a natural history where the neoplastic event aroused from the viral persistence in the resting B cells for all the life, from the genetic predisposition of the host and from the oncogenic potentialities of the virus that chronically persists and incurs reactivations.

    Really, these oncological diseases should be considered more complications than chronic forms of the illness, as well as other malignancies for which a viral – or even infectious - etiology is well recognized. The chronic diseases, in fact, should be linked in a pathogenetic and temporal way to the acute infection, from whom start the natural history of the following disease. So, as for the chronic liver diseases from HBV and HCV, it was conied the acronym of CAEBV (Chronic Active EBV infection, distinguishing within these pathologies the more severe forms (SCAEBV mostly reported in Far East and among children or adolescents. Probably only these forms have to be considered expressions of a chronic EBV infection “sensu scrictu”, together with those forms of CFS where the etiopathogenetic and temporal link with the acute EBV infection is well documented. As for CFS, also for CAEBV the criteria for a case definition were defined, even on the basis of serological and virological findings. However, the lymphoproliferative disorders are excluded from these forms and mantain their nosographic (e.g. T or B cell or NK type lymphomas and pathogenetic collocation, even when they occur within chronic forms of EBV infection. In the pathogenesis, near to the programs of latency of the virus, the genetic and environmental

  16. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

    Directory of Open Access Journals (Sweden)

    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  17. Helicobacter pylori genomic microevolution during naturally occurring transmission between adults.

    Directory of Open Access Journals (Sweden)

    Bodo Linz

    Full Text Available The human gastric pathogen Helicobacter pylori is usually acquired during childhood and, in the absence of treatment, chronic infection persists through most of the host's life. However, the frequency and importance of H. pylori transmission between adults is underestimated. Here we sequenced the complete genomes of H. pylori strains that were transmitted between spouses and analysed the genomic changes. Similar to H. pylori from chronic infection, a significantly high proportion of the determined 31 SNPs and 10 recombinant DNA fragments affected genes of the hop family of outer membrane proteins, some of which are known to be adhesins. In addition, changes in a fucosyltransferase gene modified the LPS component of the bacterial cell surface, suggesting strong diversifying selection. In contrast, virulence factor genes were not affected by the genomic changes. We propose a model of the genomic changes that are associated with the transmission and adaptation of H. pylori to a new human host.

  18. Vertical transmission of sublethal granulovirus infection in the Indian meal moth, Plodia interpunctella.

    Science.gov (United States)

    Burden, J P; Griffiths, C M; Cory, J S; Smith, P; Sait, S M

    2002-03-01

    Knowledge of the mechanisms of pathogen persistence in relation to fluctuations in host density is crucial to our understanding of disease dynamics. In the case of insect baculoviruses, which are typically transmitted horizontally via a lifestage that can persist outside the host, a key issue that remains to be elucidated is whether the virus can also be transmitted vertically as a sublethal infection. We show that RNA transcripts for the Plodia interpunctella GV granulin gene are present in a high proportion of P. interpunctella insects that survive virus challenge. Granulin is a late-expressed gene that is only transcribed after viral genome replication, its presence thus strongly indicates that viral genome replication has occurred. Almost all insects surviving the virus challenge tested positive for viral RNA in the larval and pupal stage. However, this proportion declined in the emerging adults. Granulin mRNA was also detected in both the ovaries and testes, which may represent a putative mechanism by which reduced fecundity in sublethally affected hosts might be manifested. RNA transcripts were also detected in 60-80% of second-generation larvae that were derived from mating surviving adults, but there was no difference between the sexes, with both males and females capable of transmitting a sublethal infection to their offspring. The data indicate that low-level persistent infection, with at least limited gene expression, can occur in P. interpunctella following survival of a granulovirus challenge. We believe that this is the first demonstration of a persistent, sublethal infection by a baculovirus to be initiated by a sublethal virus dose. We hypothesize that the 'latent' baculovirus infections frequently referred to in the literature may also be low level persistent, sublethal infections resulting from survival from initial baculovirus exposure.

  19. Primary varicella zoster virus infection in an Eritrean male refugee in Denmark

    DEFF Research Database (Denmark)

    Mathiasen, Victor Dahl; Wejse, Christian

    2017-01-01

    Primary infection with varicella zoster virus (VZV) in neonates, adults and in pregnancy may lead to severe disease and embryopathy. On the Northern hemisphere varicella is a mild childhood disease, but in tropical regions it typically occurs at later age and is more frequently observed among...... adolescents and adults. Disease presents with fever, malaise and a characteristic vesiculopapular rash (chickenpox) after an incubation period of 14 days on average. VZV is very contagious and transmission occurs mainly airborne. After infection, virus persists latent and prompts herpes zoster on reactivation...

  20. Two cases of neonatal adrenal hemorrhage presenting with persistent jaundice.

    Science.gov (United States)

    Ruffini, E; De Petris, L; Zorzi, G; Paoletti, P; Mambelli, G; Carlucci, A

    2013-01-01

    The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.

  1. Transmission of naturally occurring lymphoma in macaque monkeys.

    OpenAIRE

    Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

    1983-01-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

  2. Viral Interference and Persistence in Mosquito-Borne Flaviviruses

    Directory of Open Access Journals (Sweden)

    Juan Santiago Salas-Benito

    2015-01-01

    Full Text Available Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

  3. Inflation persistence and flexible prices

    OpenAIRE

    Robert Dittmar; William T. Gavin; Finn E. Kydland

    2004-01-01

    If the central bank follows an interest rate rule, then inflation is likely to be persistence, even when prices are fully flexible. Any shock, whether persistent or not, may lead to inflation persistence. In equilibrium, the dynamics of inflation are determined by the evolution of the spread between the real interest rate and the central bank’s target. Inflation persistence in U.S. data can be characterized by a vector autocorrelation function relating inflation and deviations of output from ...

  4. Fungi of genus Alternaria occurring on tomato

    Directory of Open Access Journals (Sweden)

    Joanna Marcinkowska

    2013-12-01

    Full Text Available Tomato early blight in central Poland was caused by Alternaria solani (A. porri f. sp., solani and A. alernata (A. tenuis. A. alternata was isolated more often than A. solani. All isolates of A. solani in controlled conditions killed tomato seedlings, while pathogenic isolates of A. alternata caused only slight seedling blight. In greenhouse tests A. solani proved to be strongly pathogenic for leaves and stems of tomato but A. alternata was weakly pathogenic. The latter species attacked only injured fruits while, A. solanicould penetrate through undamaged peel of fruits. Both of these species caused the same type of symptoms; the differences consisted only in intensification of disease symptoms. During 1974 and 1975 field tomatoes were moderately attacked by early blight. Thebest development of this disease occurred by the turn of August and September. Determinate variety 'New Yorker' was distinguished by more severe infection of stem parts of tomato whereas the fruits of a stock variety 'Apollo' were more strongly attacked.

  5. Novel protocol for persister cells isolation.

    Directory of Open Access Journals (Sweden)

    Silvia J Cañas-Duarte

    Full Text Available Bacterial persistence, where a fraction of a population presents a transient resistance to bactericidal substances, has great medical importance due to its relation with the appearance of antibiotic resistances and untreatable bacterial chronic infections. The mechanisms behind this phenomenon remain largely unknown in spite of recent advances, in great part because of the difficulty in isolating the very small fraction of the population that is in this state at any given time. Current protocols for persister isolation have resulted in possible biases because of the induction of this state by the protocol itself. Here we present a novel protocol that allows rapid isolation of persister cells both from exponential and stationary phase. Moreover, it is capable of differentiating between type I and type II persister cells, which should allow the field to move beyond its current state of studying only one type. While this protocol prompts a revision of many of the current results, it should greatly facilitate further advances in the field.

  6. Persister formation in Staphylococcus aureus is associated with ATP depletion

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim

    2016-04-18

    Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.

  7. Reflections on Student Persistence

    Directory of Open Access Journals (Sweden)

    Vincent Tinto

    2017-07-01

    Full Text Available The Feature for this issue Reflections on Student Persistence has been prepared by Professor Vincent Tinto, Distinguished University Professor Emeritus at Syracuse University, United States of America (USA and a longtime friend and supporter of STARS. Vincent explores the case for motivation to be considered as a significant aspect of the tertiary student psyche by drawing on theoretical frameworks, research and practical experiences related to the issue. He synthesises this extensive, detailed, rich but often somewhat impenetrable data into a trilogy of clear and credible key dimensions of the motivation construct student self efficacy, sense of belonging and perceived value of the curriculum. This interpretation of the literature is a personal but informed reflection and is a timely piece which highlights the breadth and profundity of the presentations at this year's conference in Adelaide, Australia where students in all their diversity are central to our focus on enhancing the student experience. In this opening article, Vincent refers directly to the STARS papers selected for this Conference issue of the Journal which also address the importance of student persistence, self-efficacy and building the sense of belonging within their own institutional communities (Fernandes, Ford, Rayner & Pretorius; Kahu, Nelson, & Picton; McFarlane, Spes-Skrbis & Taib; Naylor; Smallhorn. Echoing his position on social justice and his advocacy for underserved students, Vincent reminds us that educational equity gaps still exist, and he encourages us to see the issue of persistence through the eyes of the students to support their perseverance and completion and thereby help reduce educational disadvantage.

  8. A three-dimensional comparison of tick-borne flavivirus infection in mammalian and tick cell lines.

    Directory of Open Access Journals (Sweden)

    Danielle K Offerdahl

    Full Text Available Tick-borne flaviviruses (TBFV are sustained in nature through cycling between mammalian and tick hosts. In this study, we used African green monkey kidney cells (Vero and Ixodes scapularis tick cells (ISE6 to compare virus-induced changes in mammalian and arthropod cells. Using confocal microscopy, transmission electron microscopy (TEM, and electron tomography (ET, we examined viral protein distribution and the ultrastructural changes that occur during TBFV infection. Within host cells, flaviviruses cause complex rearrangement of cellular membranes for the purpose of virus replication. Virus infection was accompanied by a marked expansion in endoplasmic reticulum (ER staining and markers for TBFV replication were localized mainly to the ER in both cell lines. TEM of Vero cells showed membrane-bound vesicles enclosed in a network of dilated, anastomosing ER cisternae. Virions were seen within the ER and were sometimes in paracrystalline arrays. Tubular structures or elongated vesicles were occasionally noted. In acutely and persistently infected ISE6 cells, membrane proliferation and vesicles were also noted; however, the extent of membrane expansion and the abundance of vesicles were lower and no viral particles were observed. Tubular profiles were far more prevalent in persistently infected ISE6 cells than in acutely infected cells. By ET, tubular profiles, in persistently infected tick cells, had a cross-sectional diameter of 60-100 nm, reached up to 800 nm in length, were closed at the ends, and were often arranged in fascicle-like bundles, shrouded with ER membrane. Our experiments provide analysis of viral protein localization within the context of both mammalian and arthropod cell lines as well as both acute and persistent arthropod cell infection. Additionally, we show for the first time 3D flavivirus infection in a vector cell line and the first ET of persistent flavivirus infection.

  9. A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters

    Directory of Open Access Journals (Sweden)

    Hongxia Niu

    2015-07-01

    Full Text Available To identify effective compounds that are active against Staphylococcus aureus (S. aureus persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

  10. Persistent postsurgical pain

    DEFF Research Database (Denmark)

    Werner, Mads Utke; Bischoff, Joakim Mutahi

    2014-01-01

    The prevalences of severe persistent postsurgical pain (PPP) following breast cancer surgery (BCS), groin hernia repair (GHR), and lung cancer surgery (LCS) are 13, 2, and 4-12 %, respectively. Estimates indicate that 80,000 patients each year in the U.S.A. are affected by severe pain...... duration of surgery, repeat surgery, more invasive surgical techniques, and intraoperative nerve lesion have been associated with PPP. One of the most consistent predictive factors for PPP is high intensity acute postsurgical pain, but also psychological factors including anxiety, catastrophizing trait...

  11. Term Structure Persistence

    OpenAIRE

    Abbritti, M. (Mirko); Gil-Alana, L.A. (Luis A.); Lovcha, Y. (Yuliya); Moreno, A. (Antonio)

    2012-01-01

    Stationary I(0) models employed in yield curve analysis typically imply an unrealistically low degree of volatility in long-run short-rate expectations due to fast mean reversion. In this paper we propose a novel multivariate affine term structure model with a two-fold source of persistence in the yield curve: Long-memory and short-memory. Our model, based on an I(d) specification, nests the I(0) and I(1) models as special cases and the I(0) model is decisively rejected by the data. Our model...

  12. Infection of endothelial cells by common human viruses.

    Science.gov (United States)

    Friedman, H M

    1989-01-01

    Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

  13. Polyomavirus and Naturally Occuring Neuroglial Tumors in Raccoons (Procyon Lotor).

    Science.gov (United States)

    Pesavento, Patricia A; Brostoff, Terza; Church, Molly E; Dela Cruz, Florante N; Woolard, Kevin D

    2016-01-01

    Polyomavirus (PyV) infections are widespread in human populations and, although generally associated with silent persistence, rarely cause severe disease. Among diseases convincingly associated with natural PyV infections of humans, there are remarkably different tissue tropisms and outcomes, including progressive multifocal leukoencephalopathy, transient or progressive nephropathy, and cancer. The variable character and unpredictable outcomes of infection attest to large gaps in our basic understanding of PyV biology. In particular, the rich history of research demonstrating the oncogenic potential of PyVs in laboratory animals begs the question of why cancer is not more often associated with infection. Raccoon polyomavirus (RacPyV), discovered in 2010, is consistently identified in neuroglial tumors in free-ranging raccoons in the western United States. Exposure to RacPyV is widespread, and RacPyV is detected in tissues of raccoons without tumors. Studying the relationship of RacPyV with its natural host is a unique opportunity to uncover cogent cellular targets and protein interactions between the virus and its host. Our hypothesis is that RacPyV, as an intact episome, alters cellular pathways within neural progenitor cells and drives oncogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Persistent hyperlactacidaemia: about a clinical case.

    Science.gov (United States)

    Oliveira, Ana Rita Saraiva; Valente, Rosalina; Ramos, José; Ventura, Lurdes

    2013-05-22

    Lactate is the endogenous end product of the anaerobic glycolysis, whose production is favoured in situations of hypoperfusion or mitochondrial dysfunction. Leigh syndrome is a rare, progressive encephalomyopathy that represents a spectrum of mitochondrial genetic diseases phenotypically distinct, but with neuroradiological and pathological uniform presentation. We present the case of a 7-month-old infant, with a history of prematurity, psychomotor retardation and epilepsy, admitted to the paediatric intensive care unit (PICU) due to cardio-respiratory arrest because of respiratory infection. Hyperlactacidaemia was detected and was persistent. The study of redox potential was normal but MRI with spectroscopy identified bilateral and symmetrical lesions involving thalamic and basal ganglia, with small lactate peaks at T2 flair, findings that were suggestive of Leigh syndrome. Subsequent enzymatic study identified lack of pyruvate dehydrogenase. Persistent hyperlactacidaemia, in the appropriate clinical context, should lead to the screening of mitochondrial diseases.

  15. EAMJ Persistent 09.indd

    African Journals Online (AJOL)

    2010-04-04

    Apr 4, 2010 ... extensive research has led to the development of vaccines; reducing the mortality and the morbidity of the disease. Normally HAV infection is an acute ... He works in a cement factory where he deals with machine maintenance using lubrication oil. He is married with one child and does not report anyone at.

  16. Defining persistent hotspots

    DEFF Research Database (Denmark)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H.

    2017-01-01

    Preventive chemotherapy with praziquantel for schistosomiasis morbidity control is commonly done by mass drug administration (MDA). MDA regimen is usually based on prevalence in a given area, and effectiveness is evaluated by decreases in prevalence and/or intensity of infection after several yea...

  17. Persistence extends reciprocity.

    Science.gov (United States)

    Kurokawa, Shun

    2017-04-01

    One key potential explanation for the evolution of cooperation is conditional cooperation. This allows cooperation to evolve for cooperators who switch their behavior on the basis of information about the opponent's behavior or reputation. However, information about the opponent's behavior or reputation is sometimes unavailable, and previous studies have assumed that a player cooperates with some default probability when no information about the opponent's previous behavior or reputation is available. This default probability has been interpreted as the player's "optimism". Here, we make use of the fact that even if a player cannot observe the opponent's previous behavior or reputation, he may still condition his future behavior based on his own past behavior and in such a case, he can behave persistently. In this paper, we especially consider the case where information about the opponent's "behavior" is sometimes absent and the iterated prisoner's dilemma game between the same two individuals is played. Here, we examine the evolution of strategies that can refer to the own behavior in the previous round. Using evolutionarily stable strategy (ESS) analysis and analyzing replicator dynamics, we find that conditioning his future behavior based on his own past behavior is beneficial for the evolution. Persistence facilitates the evolution of cooperation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Persistence of airline accidents.

    Science.gov (United States)

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

  19. Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race.

    Science.gov (United States)

    Cetintas, R; Dickson, D W

    2004-12-01

    The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P

  20. Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs

    Directory of Open Access Journals (Sweden)

    Nívia Carolina Nogueira-Paiva

    2014-02-01

    Full Text Available Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78 T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

  1. Information Needs While A Disaster Is Occurring

    Science.gov (United States)

    Perry, S. C.

    2010-12-01

    Evidence from recent earthquakes, wildfires, and debris flows in southern California indicates that many people - local officials as well as residents and visitors - lack important understanding during the time that a disaster is unfolding, a time of uncertainty and confusion. While some of the uncertainty is inherent, some could be alleviated. Physical scientists and engineers know what to expect as the event unfolds. Social scientists know how humans will react during a disaster, and how to effectively communicate the warnings or evacuation orders that may precede it. Such knowledge can improve public safety. As just a few of many examples: - Based on questions posed at numerous public talks, many individuals who practice "Drop Cover and Hold" during earthquake drills do not understand what they are protecting themselves against, and thus cannot determine what to do when an earthquake strikes and they have no cover available. Similarly, they do not know how to act during the aftershocks that follow. - The 2009 Station Fire in the San Gabriel Mountains put foothills communities at risk, first from the wildfire and then from debris flows. Some neighborhoods received multiple evacuation notices during a few days or months. Local officials have expressed frustration and concern about an evacuation compliance rate that is steadily dropping and is now below 50%. The debris flow danger will persist over the next 2-4 winters yet evacuation compliance may drop lower still. - On February 6, 2010, a significant rainstorm brought the threat of imminent debris flows to areas burned by the Station Fire. In one neighborhood, residents loaded their cars with important belongings then waited for indications that they should evacuate. Powerful debris flows suddenly appeared, sweeping the cars downhill and destroying both cars and belongings. Some residents did understand that rainfall intensity would control the generation of debris flows in that storm. But they didn't understand

  2. THE MOLECULAR MECHANISMS OF EPSTEINBARR VIRUS PERSISTENCE IN THE HUMAN ORGANISM

    Directory of Open Access Journals (Sweden)

    Volyanskiy A.Yu.

    2014-12-01

    Full Text Available This review describes advances in molecular aspects of EBV infection and disease. We discuss the spectrum of clinical illness due to EBV persistent infection. The main characteristic of Epstein-Barr virus (EBV is that initial infection results in lifelong persistence. EBV infects nearly all humans by the time they reach adulthood. Healthy humans have approximately 1 to 50 infected cells per million leukocytes. EBV is one of the eight known human herpesviruses. EBV virions have a doublestranded linear DNA and 100 genes had been described in virus genome. Initial infection is thought to occur in the oral compartment. The host cells of EBV are mainly lymphocytes and epithelial cells. EBV attaches to B cells via binding of the viral gp350 protein to CD21 receptor. The consequence of EBV infection is cells proliferation and differentiation into memory B lymphocyte in the germinal center. Infected memory B cells are released into the peripheral circulation. EBV persists mostly in the memory B cell. Latency is the state of persistent viral infection without active viral production. In latently infected B cells EBV virus exist as episomes. During the latent phase episomal replication occurs via host DNA polymerase. Genes of the nuclear antigens (EBNA and latent membrane proteins (LMP are transcribed during latency. These include EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, EBNA leader protein (EBNALP, LMP1 and LMP2 genes. All nuclear antigens are transcription transactivators which bind to cis-regulatory DNA elements of cell or virus genomes directly or in complex with other proteins. LMP2A and LMP1 can function to coordinately mimic B-cell receptor and CD40 coreceptor signaling in latently infected B cells. LMP proteins activate cell signaling systems and as the consequence different gene expression programs. Characterization of gene expression patterns in different cell lines and pathologic conditions has revealed that there are at least three different

  3. Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.

    Science.gov (United States)

    Armbruster, Chelsie E; Hong, Wenzhou; Pang, Bing; Weimer, Kristin E D; Juneau, Richard A; Turner, James; Swords, W Edward

    2010-07-06

    Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

  4. Caliber-Persistent Artery

    Directory of Open Access Journals (Sweden)

    Sabrina Araújo Pinho Costa

    2015-01-01

    Full Text Available Caliber-persistent artery (CPLA of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints.

  5. An annoying persistent cough

    Directory of Open Access Journals (Sweden)

    Francesco Cipollini

    2007-03-01

    Full Text Available Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GERD was diagnosed. Although the diagnosis of chronic cough due to GERD is not easy when traditionally symptoms are not present, our case report underscores the importance of this association to the differential diagnosis of chronic cough. In these cases a relatively simple test as high dose proton pump-inhibitors trial may be useful to confirm GERD related cough.

  6. New daily persistent headache

    Directory of Open Access Journals (Sweden)

    Alok Tyagi

    2012-01-01

    Full Text Available New daily persistent headache (NDPH is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.

  7. Persistent idiopathic facial pain

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Wolfram, Frauke; Heinskou, Tone Bruvik

    2017-01-01

    Introduction: Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods...... pain 7 (13%), hypoesthesia 23 (48%), depression 16 (30%) and other chronic pain conditions 17 (32%) and a low prevalence of stabbing pain 21 (40%), touch-evoked pain 14 (26%) and remission periods 10 (19%). The odds ratio between neurovascular contact and the painful side was 1.4 (95% Cl 0.4–4.4, p = 0.......565) and the odds ratio between neurovascular contact with displacement of the trigeminal nerve and the painful side was 0.2 (95% Cl 0.0–2.1, p = 0.195). Conclusion: PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated...

  8. A transgenic mouse model for measles virus infection of the brain

    Science.gov (United States)

    Rall, Glenn F.; Manchester, Marianne; Daniels, Lia R.; Callahan, Eric M.; Belman, Alec R.; Oldstone, Michael B. A.

    1997-01-01

    In addition to the rash, fever, and upper respiratory tract congestion that are the hallmarks of acute measles virus (MV) infection, invasion of the central nervous system (CNS) can occur, establishing a persistent infection primarily in neurons. The recent identification of the human membrane glycoprotein, CD46, as the MV receptor allowed for the establishment of transgenic mice in which the CD46 gene was transcriptionally regulated by a neuron-specific promoter. Expression of the measles receptor rendered primary CD46-positive neurons permissive to infection with MV–Edmonston. Notably, viral transmission within these cultures occurred in the absence of extracellular virus, presumably via neuronal processes. No infection was seen in nontransgenic mice inoculated intracerebrally with MV–Edmonston. In contrast, scattered neurons were infected following inoculation of transgenic adults, and an impressive widespread neuronal infection was established in transgenic neonates. The neonatal infection resulted in severe CNS disease by 3–4 weeks after infection. Illness was characterized initially by awkward gait and a lack of mobility, and in later stages seizures leading to death. These results show that expression of the MV receptor on specific murine cells (neurons) in vivo is absolutely essential to confer both susceptibility to infection and neurologic disease by this human virus. The disparity in clinical findings between neonatal and adult transgenic mice indicates that differences exist between the developing and mature CNS with respect to MV infection and pathogenesis. PMID:9114047

  9. Naturally occurring flavonoids against human norovirus surrogates.

    Science.gov (United States)

    Su, Xiaowei; D'Souza, Doris H

    2013-06-01

    Naturally occurring plant-derived flavonoids are reported to have antibacterial, antiviral, and pharmacological activities. The objectives of this study were to determine the antiviral effects of four flavonoids (myricetin, L-epicatechin, tangeretin, and naringenin) on the infectivity of food borne norovirus surrogates after 2 h at 37 °C. The lab-culturable surrogates, feline calicivirus (FCV-F9) at titers of ~7 log₁₀ PFU/ml (high titer) or ~5 log₁₀ PFU/ml (low titer) and murine norovirus (MNV-1) at ~5 log₁₀ PFU/ml, were mixed with equal volumes of myricetin, L-epicatechin, tangeretin, or naringenin at concentrations of 0.5 or 1 mM, and incubated for 2 h at 37 °C. Treatments of viruses were neutralized in cell culture medium containing 10 % heat-inactivated fetal bovine serum, serially diluted, and plaque assayed. Each treatment was replicated thrice and assayed in duplicate. FCV-F9 (low titer) was not found to be reduced by tangeretin or naringenin, but was reduced to undetectable levels by myricetin at both concentrations. Low titer FCV-F9 was also decreased by 1.40 log₁₀ PFU/ml with L-epicatechin at 0.5 mM. FCV-F9 at high titers was decreased by 3.17 and 0.72 log₁₀ PFU/ml with myricetin and L-epicatechin at 0.5 mM, and 1.73 log10 PFU/ml with myricetin at 0.25 mM, respectively. However, MNV-1 showed no significant inactivation by the four tested treatments. The antiviral effects of the tested flavonoids are dependent on the virus type, titer, and dose. Further research will focus on understanding the antiviral mechanism of myricetin and L-epicatechin.

  10. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-04-13

    In this thesis, we propose a new aerial video dataset and benchmark for low altitude UAV target tracking, as well as, a photo-realistic UAV simulator that can be coupled with tracking methods. Our benchmark provides the rst evaluation of many state of-the-art and popular trackers on 123 new and fully annotated HD video sequences captured from a low-altitude aerial perspective. Among the compared trackers, we determine which ones are the most suitable for UAV tracking both in terms of tracking accuracy and run-time. We also present a simulator that can be used to evaluate tracking algorithms in real-time scenarios before they are deployed on a UAV "in the field", as well as, generate synthetic but photo-realistic tracking datasets with free ground truth annotations to easily extend existing real-world datasets. Both the benchmark and simulator will be made publicly available to the vision community to further research in the area of object tracking from UAVs. Additionally, we propose a persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc.) integrating multiple UAVs with a stabilized RGB camera. A novel strategy is employed to successfully track objects over a long period, by \\'handing over the camera\\' from one UAV to another. We integrate the complete system into an off-the-shelf UAV, and obtain promising results showing the robustness of our solution in real-world aerial scenarios.

  11. Successful heart transplantation in patients with total artificial heart infections.

    Science.gov (United States)

    Taimur, Sarah; Sullivan, Timothy; Rana, Mennakshi; Patel, Gopi; Roldan, Julie; Ashley, Kimberly; Pinney, Sean; Anyanwu, Anelechi; Huprikar, Shirish

    2018-02-01

    Data are limited on clinical outcomes in patients awaiting heart transplant (HT) with total artificial heart (TAH) infections. We retrospectively reviewed all TAH recipients at our center. TAH infection was classified as definite if a microorganism was isolated in cultures from the exit site or deep tissues around the TAH; as probable in patients without surgical or microbiologic evidence of infection but no other explanation for persistent or recurrent bloodstream infection (BSI); or possible in patients with clinical suspicion and radiographic findings suggestive of TAH infection, but without surgical intervention or microbiologic evidence. From 2012 to 2015, a total of 13 patients received a TAH, with a median age at implantation of 52 years (range: 28-60). TAH infection occurred in nine patients (seven definite, one probable, one possible) a median of 41 days after implant (range: 17-475). The majority of TAH infections were caused by Staphylococcus species. Seven of nine patients underwent HT (four had pre-HT mediastinal washout, and five had positive HT operative cultures). Three patients had an active BSI caused by the same pathogen causing TAH infection at the time of HT, with one developing a post-HT BSI with the same bacteria. No patient developed post-HT surgical site infection caused by the TAH infection pathogen. No deaths among HT recipients were attributed to infection. TAH infection is frequently associated with BSI and mediastinitis and Staphylococcus was the most common pathogen. A multimodal approach of appropriate pre- and post-HT antimicrobial therapy, surgical drainage, and heart transplantation with radical mediastinal debridement was successful in curing infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. [Epidemic of Staphylococcus aureus nosocomial infections resistant to methicillin in a maternity ward].

    Science.gov (United States)

    Le Coq, M; Simon, I; Sire, C; Tissot-Guerraz, F; Fournier, L; Aho, S; Noblot, G; Reverdy, M E; Françoise, M

    2001-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections frequently occur in the hospital environment, but their incidence is less often observed in neonates. In the present investigation, seventeen cases were recorded over a nine-week period (two cases per week). Pulsed field gradient gel electrophoresis confirmed the clonal character of the strain. The hypothesis of manually-transmitted infection due to contamination from multiple sources was reinforced by the fact the epidemic persisted in spite of the elimination of the main human infectious source and an absence of risk factors determined by the case-control study. The role of environmental factors in the persistence of this outbreak of MRSA infection has been considered.

  13. Immunology of Yersinia pestis Infection.

    Science.gov (United States)

    Bi, Yujing

    2016-01-01

    As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

  14. Persistent homology of complex networks

    International Nuclear Information System (INIS)

    Horak, Danijela; Maletić, Slobodan; Rajković, Milan

    2009-01-01

    Long-lived topological features are distinguished from short-lived ones (considered as topological noise) in simplicial complexes constructed from complex networks. A new topological invariant, persistent homology, is determined and presented as a parameterized version of a Betti number. Complex networks with distinct degree distributions exhibit distinct persistent topological features. Persistent topological attributes, shown to be related to the robust quality of networks, also reflect the deficiency in certain connectivity properties of networks. Random networks, networks with exponential connectivity distribution and scale-free networks were considered for homological persistency analysis

  15. Development of functional gastrointestinal disorders after Giardia lamblia infection

    Directory of Open Access Journals (Sweden)

    Hanevik Kurt

    2009-04-01

    Full Text Available Abstract Background Functional gastrointestinal disorders (FGID may occur following acute gastroenteritis. This long-term complication has previously not been described after infection with the non-invasive protozoan Giardia lamblia. This study aims to characterize persistent abdominal symptoms elicited by Giardia infection according to Rome II criteria and symptoms scores. Methods Structured interview and questionnaires 12–30 months after the onset of Giardia infection, and at least 6 months after Giardia eradication, among 82 patients with persisting abdominal symptoms elicited by the Giardia infection. All had been evaluated to exclude other causes. Results We found that 66 (80.5% of the 82 patients had symptoms consistent with irritable bowel syndrome (IBS and 17 (24.3% patients had functional dyspepsia (FD according to Rome II criteria. IBS was sub classified into D-IBS (47.0%, A-IBS (45.5% and C-IBS (7.6%. Bloating, diarrhoea and abdominal pain were reported to be most severe. Symptoms exacerbation related to specific foods were reported by 45 (57.7% patients and to physical or mental stress by 34 (44.7% patients. Conclusion In the presence of an IBS-subtype pattern consistent with post-infectious IBS (PI-IBS, and in the absence of any other plausible causes, we conclude that acute Giardia infection may elicit functional gastrointestinal diseases with food and stress related symptoms similar to FGID patients in general.

  16. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  17. Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin

    Directory of Open Access Journals (Sweden)

    Rebecca Yee

    2015-12-01

    Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.

  18. Variable Persister Gene Interactions with (pppGpp for Persister Formation in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Shuang Liu

    2017-09-01

    Full Text Available Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA system HipAB depends on stringent response effector (pppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (pppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ using Escherichia coli as a model. By comparing the persister levels of wild type with their single gene knockout and double knockout mutants with relA, we divided their interactions into five types, namely A “dependent” (dnaK, recA, B “positive reinforcement” (rpoS, pspF, ssrA, recA, C “antagonistic” (clpB, sucB, umuD, uvrA, hipA, mqsR, relE, dinJ, D “epistasis” (clpB, rpoS, tnaA, ssrA, smpB, hipA, and E “irrelevant” (dnaK, clpB, rpoS, tnaA, sucB, smpB, umuD, uvrA, hipA, mqsR, relE, dinJ. We found that the persister gene interactions are intimately dependent on bacterial culture age, cell concentrations (diluted versus undiluted culture, and drug classifications, where the same gene may belong to different groups with varying antibiotics, culture age or cell concentrations. Together, this study represents the first attempt to systematically characterize the intricate relationships among the different mechanisms of persistence and as such provide new insights into the complexity of the persistence phenomenon at the level of persister gene network interactions.

  19. Cerebrospinal Fluid Proteomics Reveals Potential Pathogenic Changes in the Brains of SIV-infected Monkeys

    OpenAIRE

    Pendyala, Gurudutt; Trauger, Sunia A.; Kalisiak, Ewa; Ellis, Ronald J.; Siuzdak, Gary; Fox, Howard S.

    2009-01-01

    The HIV-1-associated neurocognitive disorder occurs in approximately one-third of infected individuals. It has persisted in the current era of anti-retroviral therapy, and its study is complicated by the lack of biomarkers for this condition. Since the cerebrospinal fluid is the most proximal biofluid to the site of pathology, we studied the cerebrospinal fluid in a nonhuman primate model for HIV-1-associated neurocognitive disorder. Here we present a simple and efficient liquid chromatograph...

  20. Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children : Splenectomy in ITP.

    Science.gov (United States)

    Ahmed, Rayaz; Devasia, Anup J; Viswabandya, Auro; Lakshmi, Kavitha M; Abraham, Aby; Karl, Sampath; Mathai, John; Jacob, Paul M; Abraham, Deepak; Srivastava, Alok; Mathews, Vikram; George, Biju

    2016-09-01

    The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.

  1. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  2. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  3. Microbial Biofilms: Persisters, Tolerance and Dosing

    Science.gov (United States)

    Cogan, N. G.

    2005-03-01

    Almost all moist surfaces are colonized by microbial biofilms. Biofilms are implicated in cross-contamination of food products, biofouling, medical implants and various human infections such as dental cavities, ulcerative colitis and chronic respiratory infections. Much of current research is focused on the recalcitrance of biofilms to typical antibiotic and antimicrobial treatments. Although the polymer component of biofilms impedes the penetration of antimicrobials through reaction-diffusion limitation, this does not explain the observed tolerance, it merely delays the action of the agent. Heterogeneities in growth-rate also slow the eradication of the bacteria since most antimicrobials are far less effective for non-growing, or slowly growing bacteria. This also does not fully describe biofilm tolerance, since heterogeneities arr primairly a result of nutrient consumption. In this investigation, we describe the formation of `persister' cells which neither grow nor die in the presence of antibiotics. We propose that the cells are of a different phenotype than typical bacterial cells and the expression of the phenotype is regulated by the growth rate and the antibiotic concentration. We describe several experiments which describe the dynamics of persister cells and which motivate a dosing protocol that calls for periodic dosing of the population. We then introduce a mathematical model, which describes the effect of such a dosing regiment and indicates that the relative dose/withdrawal times are important in determining the effectiveness of such a treatment. A reduced model is introduced and the similar behavior is demonstrated analytically.

  4. The persistence of depression score

    NARCIS (Netherlands)

    Spijker, J.; de Graaf, R.; Ormel, J.; Nolen, W. A.; Grobbee, D. E.; Burger, H.

    2006-01-01

    Objective: To construct a score that allows prediction of major depressive episode (MDE) persistence in individuals with MDE using determinants of persistence identified in previous research. Method: Data were derived from 250 subjects from the general population with new MDE according to DSM-III-R.

  5. Genomic and transcriptomic analysis of Escherichia coli strains associated with persistent and transient bovine mastitis and the role of colanic acid

    Science.gov (United States)

    Escherichia coli is a leading cause of bacterial mastitis in dairy cattle. This infection is most often transient in nature, causing an infection that lasts 2–3 days. However, E. coli has been shown to cause a persistent infection in a minority of cases. The mechanisms that allow for a persistent E....

  6. Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2009-11-01

    Full Text Available Simian varicella virus (SVV, the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV. Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

  7. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

    Science.gov (United States)

    Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

    2018-06-01

    The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Prevalence and treatment of persistent pulmonary hypertension in the newborn in a Mexican pediatric hospital.

    Science.gov (United States)

    Ortiz, Mario I; Estévez-Castillo, Ramón; Bautista-Rivas, Martha M; Romo-Hernández, Georgina; López-Cadena, Juan M; Copca-García, José A

    2010-01-01

    Persistent pulmonary hypertension of the newborn is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome characterized by marked pulmonary hypertension that causes hypoxemia and right-to-left extra-pulmonary shunting of blood. In the treatment of persistent pulmonary hypertension of the newborn, the goal is to increase oxygen flow to the baby's organs to prevent serious health problems. Treatment may include medication, mechanical ventilation and respiratory therapy. We performed a retrospective, descriptive and transversal study to investigate the prevalence and treatment of neonatal patients with persistent pulmonary hypertension who were admitted at the Hospital del Niño DIF from 2004 to 2008. Data, collected from hospital charts, included demographic, clinical course and use of medication. A total of 38 patients were included (prevalence of 5.7%). The average age of patients was 8.4 +/- 1.4 days. The mortality rate was 42.1%. Data were collected and 45 different drugs were given to the pediatric patients. The median number of drugs/inpatient was 8.3 (1-18). The therapeutic class most prescribed was anti-infective (29.9% of all the prescriptions), followed by cardiovascular and renal drugs (26.4% of all the prescriptions) and gastrointestinal agents (14.6% of all the prescriptions). Ranitidine was the drug most commonly used, followed by ampicillin and midazolam. We found a high mortality rate and as in many studies, the therapeutic class most used were anti-infectives.

  9. Modelling the role of Tax expression in HTLV-I persistence in vivo.

    Science.gov (United States)

    Li, Michael Y; Lim, Aaron G

    2011-12-01

    Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

  10. Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence.

    Science.gov (United States)

    Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Charleston, Bryan; Juleff, Nicholas

    2016-05-15

    Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more

  11. Vaginal Infections

    Science.gov (United States)

    ... gov/ Home Body Your reproductive health Vaginal infections Vaginal infections Help for infections If you have pain, ... infections and how to prevent them. Types of vaginal infections top Two common vaginal infections are bacterial ...

  12. Infective Endocarditis

    Science.gov (United States)

    ... Center > Infective Endocarditis Menu Topics Topics FAQs Infective Endocarditis En español Infective endocarditis is an infection of ... time, congestive heart failure (CHF). What causes infective endocarditis? The infection that leads to endocarditis can be ...

  13. Persistent G. lamblia impairs growth in a murine malnutrition model.

    Science.gov (United States)

    Bartelt, Luther A; Roche, James; Kolling, Glynis; Bolick, David; Noronha, Francisco; Naylor, Caitlin; Hoffman, Paul; Warren, Cirle; Singer, Steven; Guerrant, Richard

    2013-06-01

    Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/ subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia– potentiated growth decrements.

  14. Persistence, resistance, resonance

    Science.gov (United States)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  15. Prolonged persistence of bovine herpesvirus in small cattle herds: a model-based analysis

    NARCIS (Netherlands)

    Mollema, E.; Jong, de M.C.M.; Boven, van R.M.

    2005-01-01

    Herpesviruses can remain dormant in once-infected hosts and, upon reactivation, cause such hosts to become infectious. This phenomenon of latency and reactivation may enable herpesviruses to persist for a long time in small host populations. To quantify the effect of reactivation on persistence, the

  16. DNA-crosslinker cisplatin eradicates bacterial persister cells.

    Science.gov (United States)

    Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

    2016-09-01

    For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Immunological aspects of Giardia infections

    OpenAIRE

    Heyworth Martin F.

    2014-01-01

    Immunodeficiency, particularly antibody deficiency, predisposes to increased intensity and persistence of Giardia infections. Giardia-infected immunocompetent hosts produce serum and intestinal antibodies against Giardia trophozoites. The number of Giardia muris trophozoites, in mice with G. muris infection, is reduced by intra-duodenal administration of anti-G. muris antibody. Giardia intestinalis antigens that are recognised by human anti-trophozoite antibodies include variable (variant-spe...

  18. Efficacy of standard therapies against Ureaplasma species and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial.

    Science.gov (United States)

    Khosropour, Christine M; Manhart, Lisa E; Gillespie, Catherine W; Lowens, M Sylvan; Golden, Matthew R; Jensen, Nicole L; Kenny, George E; Totten, Patricia A

    2015-08-01

    Ureaplasma urealyticum biovar 2 (UU-2), but not Ureaplasma parvum (UP), has been associated with non-gonococcal urethritis (NGU), but little is known about species-specific responses to standard therapies. We examined species-specific treatment outcomes and followed men with treatment failure for 9 weeks. From May 2007 to July 2011, men aged ≥16 attending a sexually transmitted disease (STD) clinic in Seattle, Washington, with NGU (urethral discharge or urethral symptoms plus ≥5 polymorphonuclear leucocytes /high-powered field) enrolled in a double-blind, randomised trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice a day ×7 days) + placebo azithromycin. Ureaplasma were detected in culture followed by species-specific PCR. Outcomes were assessed at 3, 6 and 9 weeks. At 3 weeks, men with persistent Ureaplasma detection received 'reverse therapy' (e.g., active doxycycline if they first received active azithromycin). At 6 weeks, persistently positive men received moxifloxacin (400 mg×7 days). Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP, respectively, and returned at 3 weeks. Persistent detection was similar for UU-2-infected men initially treated with azithromycin or doxycycline (25% vs. 31%; p=0.53), but differed somewhat for men with UP (45% vs. 24%; p=0.11). At 6 weeks, 57% of UU-2-infected and 63% of UP-infected men who received both drugs had persistent detection. Failure after moxifloxacin occurred in 30% and 36%, respectively. Persistent detection of UU-2 or UP was not associated with signs/symptoms of NGU. Persistent detection after treatment with doxycycline, azithromycin and moxifloxacin was common for UU and UP, but not associated with persistent urethritis. NCT00358462. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. On the Issue of Herpes Infection as an Actual Problem Nowadays

    Directory of Open Access Journals (Sweden)

    V.P. Borak

    2016-04-01

    Full Text Available Among persistent intracellular agents, a group of herpesviruses occupies the leading place after the prevalence. The World Health Organization (WHO warns the international community of the danger of latent herpes infection pandemic. According to the WHO, 70 to 90 % of the world population is infected with one or more types of herpes virus, and in 50 % of them, due to the absence of stable immunity, disease relapses occur annually. The family of herpes viruses found in humans includes herpes simplex virus type 1 and 2, Zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes type 6, 7, 8. Thus, in the pathogenesis of herpes infection type 1 and 2, there are four main phases: the penetration of the epithelial cells → penetration into the nerve endings and paravertebral ganglia → elimination of the virus from tissues and organs → reactivation of herpes simplex virus and moving it to the port of infection. Herpetic and cytomegalovirus infection that belongs to the group of TORCH infections is the most common cause fetal infection, which can lead to the birth of a child with disabilities. Herpesvirus infections are considered as a group of infections associated with human immunodeficiency syndrome, and is a common cause of damage to the central nervous system and internal organs in patients with secondary immunodeficiency. Almost all known now human herpesviruses can cause damage to the nervous system. In this regard, herpes infections have become one of the leading medical and social problems and acquire national importance.

  20. Mouse adenovirus type 1 infection of macrophages

    NARCIS (Netherlands)

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  1. Udder infections with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis at calving in dairy herds with suboptimal udder health.

    Science.gov (United States)

    Lundberg, Å; Nyman, A-K; Aspán, A; Börjesson, S; Unnerstad, H Ericsson; Waller, K Persson

    2016-03-01

    Udder infections with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis are common causes of bovine mastitis. To study these pathogens in early lactation, a 12-mo longitudinal, observational study was carried out in 13 herds with suboptimal udder health. The aims of the study were to investigate the occurrence of these pathogens and to identify if presence of the 3 pathogens, and of genotypes within the pathogens, differed with respect to herd, season, and parity. Quarter milk samples, collected at calving and 4 d in milk (DIM), were cultured for the 3 pathogens. Genotyping of staphylococcal and streptococcal isolates was performed using spa typing and pulsed-field gel electrophoresis, respectively. For each of the 3 pathogens, cows with an udder infection at calving or 4 DIM were allocated to 1 of 4 infection types: cleared (pathogen present only at calving), persistent (pathogen present in the same quarter at calving and 4 DIM), new (pathogen present only at 4 DIM), or cleared/new (pathogen present in 1 quarter at calving and in another quarter at 4 DIM). Associations between season or parity and overa