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Sample records for establishes latent infection

  1. A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

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    Sara Campos da Silva

    2011-05-01

    Full Text Available Mutant viral strains deleted in non-essential genes represent useful tools to study the function of specific gene products in the biology of the virus. We herein describe an investigation on the phenotype of a bovine herpesvirus 5 (BoHV-5 recombinant deleted in the gene encoding the enzyme thymidine kinase (TK in rabbits, with special emphasis to neuroinvasiveness and the ability to establish and reactivate latent infection. Rabbits inoculated with the parental virus (SV-507/99 (n=18 at a low titer (10(5.5TCID50 shed virus in nasal secretions in titers up to 10(4.5TCID50 for up to 12 days (average: 9.8 days [5-12] and 5/ 16 developed neurological disease and were euthanized in extremis. Rabbits inoculated with the recombinant BoHV-5TKΔ at a high dose (10(7.1TCID50 also shed virus in nasal secretions, yet to lower titers (maximum: 10(2.3TCID50 and for a shorter period (average: 6.6 days [2-11] and remained healthy. PCR examination of brain sections of inoculated rabbits at day 6 post-infection (pi revealed a widespread distribution of the parental virus, whereas DNA of the recombinant BoHV-5TKΔ-was detected only in the trigeminal ganglia [TG] and olfactory bulbs [OB]. Nevertheless, during latent infection (52pi, DNA of the recombinant virus was detected in the TGs, OBs and also in other areas of the brain, demonstrating the ability of the virus to invade the brain. Dexamethasone (Dx administration at day 65 pi was followed by virus reactivation and shedding by 5/8 rabbits inoculated with the parental strain (mean duration of 4.2 days [1 - 9] and by none of seven rabbits inoculated with the recombinant virus. Again, PCR examination at day 30 post-Dx treatment revealed the presence of latent DNA in the TGs, OBs and in other areas of the brain of both groups. Taken together, these results confirm that the recombinant BoHV-5TKΔ is highly attenuated for rabbits. It shows a reduced ability to replicate in the nose but retains the ability to invade

  2. FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

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    Murphy Brian

    2012-02-01

    Full Text Available Abstract Background Feline immunodeficiency virus (FIV is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. Results In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Conclusions Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.

  3. A primary cell model of HIV-1 latency that uses activation through the T cell receptor and return to quiescence to establish latent infection

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    Kim, Michelle; Hosmane, Nina N.; Bullen, C. Korin; Capoferri, Adam; Yang, Hung-Chih; Siliciano, Janet D.; Siliciano, Robert F.

    2015-01-01

    A mechanistic understanding of HIV-1 latency depends upon a model system that recapitulates the in vivo condition of latently infected, resting CD4+ T lymphocytes. Latency appears to be established after activated CD4+ T cells, the principal targets of HIV-1 infection, become productively infected and survive long enough to return to a resting memory state in which viral expression is inhibited by changes in the cellular environment. This protocol describes an ex vivo primary cell system that is generated under conditions that reflect the in vivo establishment of latency. Creation of these latency model cells takes 12 weeks and, once established, the cells can be maintained and used for several months. The resulting cell population contains both uninfected and latently infected cells. This primary cell model can be used to perform drug screens, study CTL responses to HIV-1, compare viral alleles, or to expand the ex vivo lifespan of cells from HIV-1 infected individuals for extended study. PMID:25375990

  4. EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

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    Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

    2018-06-01

    Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

  5. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  6. Treatment of Latent Tuberculosis Infection

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    Tang, Patrick; Johnston, James

    2017-01-01

    Opinion statement The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and ac...

  7. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.

  8. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

  9. Managing latent tuberculosis infection and tuberculosis in children

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    I. Carvalho

    2018-03-01

    Full Text Available Tuberculosis (TB is a major cause of childhood morbidity and mortality worldwide. The aim of this review is to describe the management of the child with TB and latent tuberculosis infection (LTBI.To develop this article, a working group reviewed relevant epidemiological and other scientific studies and established practices in conducting LBTI and TB in children. The article describes how to manage the child with LTBI, considering transmission and infectiousness of tuberculosis, contact screening and prioritization of contacts and recommendations on treatment of children with LTBI and how to manage the child with TB considering the susceptibility of children to developing tuberculosis, epidemiology and classification of tuberculosis in children, diagnosis and treatment. Keywords: Tuberculosis, Pediatric, Childhood, Latent tuberculosis infection

  10. A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion.

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    Liu, Yuehong; Li, Shufeng

    2015-01-01

    Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.

  11. Effect of Acycloguanosine Treatment on Acute and Latent Herpes Simplex Infections in Mice

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    Field, Hugh J.; Bell, Susanne E.; Elion, Gertrude B.; Nash, Anthony A.; Wildy, Peter

    1979-01-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form. PMID:464587

  12. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice.

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    Field, H J; Bell, S E; Elion, G B; Nash, A A; Wildy, P

    1979-04-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.

  13. Homeostatic proliferation fails to efficiently reactivate HIV-1 latently infected central memory CD4+ T cells.

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    Alberto Bosque

    2011-10-01

    Full Text Available Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.

  14. Cytomegalovirus establishes a latent reservoir and triggers long-lasting inflammation in the eye.

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    Valentina Voigt

    2018-05-01

    Full Text Available Recent outbreaks of Ebola and Zika have highlighted the possibility that viruses may cause enduring infections in tissues like the eye, including the neural retina, which have been considered immune privileged. Whether this is a peculiarity of exotic viruses remains unclear, since the impact of more common viral infections on neural compartments has not been examined, especially in immunocompetent hosts. Cytomegalovirus is a common, universally distributed pathogen, generally innocuous in healthy individuals. Whether in immunocompetent hosts cytomegalovirus can access the eye, and reside there indefinitely, was unknown. Using the well-established murine cytomegalovirus infection model, we show that systemic infection of immunocompetent hosts results in broad ocular infection, chronic inflammation and establishment of a latent viral pool in the eye. Infection leads to infiltration and accumulation of anti-viral CD8+ T cells in the eye, and to the development of tissue resident memory T cells that localize to the eye, including the retina. These findings identify the eye as an unexpected reservoir for cytomegalovirus, and suggest that common viruses may target this organ more frequently than appreciated. Notably, they also highlight that infection triggers sustained inflammatory responses in the eye, including the neural retina.

  15. Latent Toxoplasma gondii infection leads to improved action control.

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    Stock, Ann-Kathrin; Heintschel von Heinegg, Evelyn; Köhling, Hedda-Luise; Beste, Christian

    2014-03-01

    The parasite Toxoplasma gondii has been found to manipulate the behavior of its secondary hosts to increase its own dissemination which is commonly believed to be to the detriment of the host (manipulation hypothesis). The manipulation correlates with an up-regulation of dopaminergic neurotransmission. In humans, different pathologies have been associated with T. gondii infections but most latently infected humans do not seem to display overt impairments. Since a dopamine plus does not necessarily bear exclusively negative consequences in humans, we investigated potential positive consequences of latent toxoplasmosis (and the presumed boosting of dopaminergic neurotransmission) on human cognition and behavior. For this purpose, we focused on action cascading which has been shown to be modulated by dopamine. Based on behavioral and neurophysiological (EEG) data obtained by means of a stop-change paradigm, we were able to demonstrate that healthy young humans can actually benefit from latent T. gondii infection as regards their performance in this task (as indicated by faster response times and a smaller P3 component). The data shows that a latent infection which is assumed to affect the dopaminergic system can lead to paradoxical improvements of cognitive control processes in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

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    Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

    2017-10-17

    The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

  17. Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner.

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    Rajeev Mehla

    2010-06-01

    Full Text Available HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC -alpha and -delta, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC involving stress induced AMP Kinase (AMPK inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs.

  18. Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection

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    Benjamin A. Krishna

    2017-12-01

    Full Text Available Reactivation of human cytomegalovirus (HCMV latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR, which, during lytic infection, is a constitutive cell-signaling activator. Here we now show that in monocytes, which are recognized sites of HCMV latency in vivo, US28 attenuates multiple cell signaling pathways, including mitogen-activated protein (MAP kinase and NF-κB, and that this is required to establish a latent infection; viruses deleted for US28 initiate a lytic infection in infected monocytes. We also show that these monocytes then become potent targets for the HCMV-specific host immune response and that latently infected cells treated with an inverse agonist of US28 also reactivate lytic infection and similarly become immune targets. Consequently, we suggest that the use of inhibitors of US28 could be a novel immunotherapeutic strategy to reactivate the latent viral reservoir, allowing it to be targeted by preexisting HCMV-specific T cells.

  19. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

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    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    macrophages persist despite ART. Markers of macrophage activation and neuronal damage are observed in the CSF of HIV-infected individuals and of SIV-infected macaques on suppressive ART regimens, suggesting that the CNS has continued virus infection and latent infection. A controversy exists as to whether brain macrophages represent a latent source of replication-competent virus capable of reestablishing infection upon treatment interruption. In this study, we demonstrated the presence of the latent macrophage reservoir in brains of SIV-infected ART-treated macaques and analyzed the reservoir using our established outgrowth assay to quantitate macrophages harboring replication-competent SIV genomes. Our results support the idea of the existence of other latent reservoirs in addition to resting CD4 + T cells and underscore the importance of macrophages in developing strategies to eradicate HIV. Copyright © 2017 Avalos et al.

  20. Investigation of latent infections caused by cyprinid herpesvirus 3 in koi ( Cyprinus carpio) in southern China.

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    Zheng, Shucheng; Wang, Qing; Bergmann, Sven M; Li, Yingying; Zeng, Weiwei; Wang, Yingying; Liu, Chun; Shi, Cunbin

    2017-05-01

    Although herpesviruses such as cyprinid herpesvirus 3 (CyHV-3) can establish lifelong latent infections, little is known about latency conditions in farmed koi populations in China. We used nested polymerase chain reaction targeting the TK gene and an indirect antibody ELISA to screen asymptomatic fish obtained from southern China for evidence of CyHV-3 infection. CyHV-3 DNA could be detected either in peripheral blood leukocytes or from gills of asymptomatic koi. Most koi sera did not contain anti-CyHV-3 antibodies; however, 5 samples were ELISA positive, providing evidence of prior CyHV-3 infections. These findings suggest that koi may survive CyHV-3 infections and become virus carriers.

  1. National position statement for the management of latent tuberculosis infection.

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    Stock, David

    2017-09-01

    The primary role of any tuberculosis (TB) control program is to ensure the prompt identification and effective treatment of active disease. The host immune system often succeeds in containing the initial (or primary) infection with Mycobacterium tuberculosis (Mtb), but may fail to eliminate the pathogen. The persistence of viable organisms explains the potential for the development of active disease years or even decades after infection. This is known as latent tuberculosis infection (LTBI) although, rather than a distinct entity, this probably represents part of a dynamic spectrum. Individuals with LTBI are asymptomatic and it is therefore clinically undetectable. The World Health Organization (WHO) estimates that one-third of the global population has been infected with Mtb, with highest prevalence of LTBI in countries/regions with the highest prevalence of active disease. In 2013, 88% of 1322 notifications in Australia were in the overseas-born population (incidence 19.5 per 100,000 v. 1.0 per 100,000), with this proportion rising over the course of the last decade. Combined with epidemiological evidence of low local transmission, this strongly implies that the vast majority resulted from reactivation of latent infection acquired prior to immigration. Contrasting trends in TB incidence in other developed countries probably reflect differences in policy regarding LTBI. The diagnosis and treatment of LTBI represents an important opportunity for intervention by jurisdictional TB control programs. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or

  2. Latent M. tuberculosis infection--pathogenesis, diagnosis, treatment and prevention strategies.

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    Druszczyńska, Magdalena; Kowalewicz-Kulbat, Magdalena; Fol, Marek; Włodarczyk, Marcin; Rudnicka, Wiesława

    2012-01-01

    One third of the earths population is infected with Mycobacterium tuberculosis (Mtb), but only 5-10% of the infected individuals develop active tuberculosis (TB) over their lifetime. The remaining 90-95% stay healthy and are called latently infected individuals. They are the biggest reservoir of the tubercle bacilli and identifying the cases of latent TB is a part of the global plan of TB control. From the clinical point of view detection of latent TB infections (LTBI) in individuals with the highest active TB risk including cases of HIV infection, autoimmune inflammatory diseases or cancer, is a priority. This review summarizes the recent findings in the pathogenesis of latent TB, its diagnosis, treatment and prevention.

  3. Latent tuberculous infection screening using recombinant tuberculous allergen

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    N. A. Barmina

    2016-01-01

    Full Text Available In recent years the significant deterioration of health has been observed in schoolchildren. As per official data only 20% of children graduating from school are considered to be completely healthy, and 60% suffer from chronic diseases, i.e. belong to health groups III, IV and V, among which there are many children belonging to tuberculosis risk groups and suffering from undetected latent tuberculous infection. The efficiency of the new technique aimed to detect active tuberculous infection in children and adolescents of health groups III, IV and V has been evaluated. Screening proved the reduction in the number of patients in need of TB doctor advising by 8.4 fold compared to traditional mass diagnostics with tuberculin. Hyperergic reactions to diaskintest are 6 fold less common compared to Mantoux test. And 99.2% of children referred to TB doctor were registered to the dispensary follow-up versus 23.4% of children referred to TB doctor as per mass tuberculin testing results. (p < 0.001. Thus the validity of referral to TB doctor increased 4.2 fold. The detection rate of active forms of tuberculosis made 0.4 per 1000 examinations versus 0.1 in case of mass screening with tuberculin testing.

  4. Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.

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    Agaya, Janet; Nnadi, Chimeremma D; Odhiambo, Joseph; Obonyo, Charles; Obiero, Vincent; Lipke, Virginia; Okeyo, Elisha; Cain, Kevin; Oeltmann, John E

    2015-12-01

    To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers. © 2015 John Wiley & Sons Ltd.

  5. Prevalence of latent Mycobacterium tuberculosis infection in prisoners.

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    Navarro, Pedro Daibert de; Almeida, Isabela Neves de; Kritski, Afrânio Lineu; Ceccato, Maria das Graças; Maciel, Mônica Maria Delgado; Carvalho, Wânia da Silva; Miranda, Silvana Spindola de

    2016-01-01

    To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system. Determinar a prevalência e os fatores associados à infecção latente por Mycobacterium tuberculosis (ILTB) em pessoas privadas de liberdade no Estado de Minas Gerais. Estudo de coorte transversal realizado em duas penitenciárias em Minas Gerais. Foi realizada a prova tuberculínica nos indivíduos que aceitaram participar do estudo. Foram selecionados 1.120 indivíduos para a pesquisa. A prevalência da ILTB foi de 25,2%. Na análise multivariada, a ILTB esteve associada com relato de contato com caso de tuberculose ativa dentro da penitenciária (OR ajustada = 1,51; IC95%: 1

  6. Prevalence of latent Mycobacterium tuberculosis infection among professionals of the primary healthcare network

    Directory of Open Access Journals (Sweden)

    Tássia Silvana Borges

    2014-06-01

    Full Text Available Objective: To estimate the prevalence of latent M. tuberculosis infection and identify characteristics related to latent infection among workers of the primary healthcare network.Methods: Cross-sectional, observational and descriptive study, conducted in 2011, included 137 basic health workers who performed their activities in a municipality. Interviews were carried out addressing characteristics of exposure at work (BCG vaccination, length of time working in the health system, potential exposure to tuberculosis, HIV infection, use of corticosteroids, diabetes, use of tobacco or alcohol and subsequently performed tuberculin skin test (TST. Data was analyzed with Fischer and Student’s t-test (p < 0.05. Results: Health professionals were mostly women (n=126, 92% with mean age of 35.3 (± 9.1 years. Among the reactors, 25 (55.5% sought medical care, and of these, 7 (28% underwent prophylactic treatment. The prevalence of latent tuberculosis was 32.8%. Of the characteristics evaluated, only smoking (OR 3.03; 95%CI 1.05-8.77 was associated with latent infection. Conclusion: The estimated prevalence of latent M. tuberculosis infection among the evaluated health workers was 32.8%. As for the characteristics studied, it was not possible to relate them to latent infection among workers in primary healthcare network, with the exception of the smoking habit. doi: 10.5020/18061230.2014.p269

  7. A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children

    Science.gov (United States)

    Persaud, Deborah; Pierson, Theodore; Ruff, Christian; Finzi, Diana; Chadwick, Karen R.; Margolick, Joseph B.; Ruff, Andrea; Hutton, Nancy; Ray, Stuart; Siliciano, Robert F.

    2000-01-01

    HIV-1 persists in a latent state in resting CD4+ T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4+ T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4+ T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1–3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4+ T cells will be a major obstacle to HIV-1 eradication in children. PMID:10749578

  8. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics

    Science.gov (United States)

    Hosmane, Nina N.; Kwon, Kyungyoon J.; Bruner, Katherine M.; Capoferri, Adam A.; Rosenbloom, Daniel I.S.; Keele, Brandon F.; Ho, Ya-Chi

    2017-01-01

    A latent reservoir for HIV-1 in resting CD4+ T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. PMID:28341641

  9. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics.

    Science.gov (United States)

    Hosmane, Nina N; Kwon, Kyungyoon J; Bruner, Katherine M; Capoferri, Adam A; Beg, Subul; Rosenbloom, Daniel I S; Keele, Brandon F; Ho, Ya-Chi; Siliciano, Janet D; Siliciano, Robert F

    2017-04-03

    A latent reservoir for HIV-1 in resting CD4 + T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. © 2017 Hosmane et al.

  10. Establishment of Chronic Infection: Brucella's Stealth Strategy

    Science.gov (United States)

    Ahmed, Waqas; Zheng, Ke; Liu, Zheng-Fei

    2016-01-01

    Brucella is a facultative intracellular pathogen that causes zoonotic infection known as brucellosis which results in abortion and infertility in natural host. Humans, especially in low income countries, can acquire infection by direct contact with infected animal or by consumption of animal products and show high morbidity, severe economic losses and public health problems. However for survival, host cells develop complex immune mechanisms to defeat and battle against attacking pathogens and maintain a balance between host resistance and Brucella virulence. On the other hand as a successful intracellular pathogen, Brucella has evolved multiple strategies to evade immune response mechanisms to establish persistent infection and replication within host. In this review, we mainly summarize the “Stealth” strategies employed by Brucella to modulate innate and the adaptive immune systems, autophagy, apoptosis and possible role of small noncoding RNA in the establishment of chronic infection. The purpose of this review is to give an overview for recent understanding how this pathogen evades immune response mechanisms of host, which will facilitate to understanding the pathogenesis of brucellosis and the development of novel, more effective therapeutic approaches to treat brucellosis. PMID:27014640

  11. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

    NARCIS (Netherlands)

    Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

    2015-01-01

    Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health

  12. Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

    Science.gov (United States)

    Diaz, Fernando M; Knipe, David M

    2016-01-15

    Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    Science.gov (United States)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

  14. Isoniazid Completion Rates for Latent Tuberculosis Infection among College Students Managed by a Community Pharmacist

    Science.gov (United States)

    Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

    2009-01-01

    Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants: Participants were university students diagnosed with…

  15. "Latent" infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults.

    Science.gov (United States)

    Cook, Thomas B; Brenner, Lisa A; Cloninger, C Robert; Langenberg, Patricia; Igbide, Ajirioghene; Giegling, Ina; Hartmann, Annette M; Konte, Bettina; Friedl, Marion; Brundin, Lena; Groer, Maureen W; Can, Adem; Rujescu, Dan; Postolache, Teodor T

    2015-01-01

    Latent chronic infection with Toxoplasma gondii (T. gondii), a common neurotropic pathogen, has been previously linked with suicidal self-directed violence (SSDV). We sought to determine if latent infection with T. gondii is associated with trait aggression and impulsivity, intermediate phenotypes for suicidal behavior, in psychiatrically healthy adults. Traits of aggression and impulsivity were analyzed in relationship to IgG antibody seropositivity for T. gondii and two other latent neurotropic infections, herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV). One thousand community-residing adults residing in the Munich metropolitan area with no Axis I or II conditions by SCID for DSM-IV (510 men, 490 women, mean age 53.6 ± 15.8, range 20-74). Plasma samples were tested for IgG antibodies to T. gondii, HSV-1 and CMV by ELISA. Self-reported ratings of trait aggression scores (Questionnaire for Measuring Factors of Aggression [FAF]) and trait impulsivity (Sensation-Seeking Scale-V [SSS-V]) were analyzed using linear multivariate methods. T. gondii IgG seropositivity was significantly associated with higher trait reactive aggression scores among women (p impulsive sensation-seeking (SSS-V Disinhibition) among younger men (p impulsivity, personality traits considered as endophenotypes for SSDV, are associated with latent T. gondii infection in a gender and age-specific manner, and could be further investigated as prognostic and treatment targets in T. gondii-positive individuals at risk for SSDV. Published by Elsevier Ltd.

  16. Policy and practice of programmatic management of latent tuberculosis infection in The Netherlands

    NARCIS (Netherlands)

    de Vries, G. (Gerard); R.M. van Hest (Reinier); M. Bakker (Marleen); C.G.M. Erkens (C. G M); S. van den Hof (S.); Meijer, W. (Wieneke); Oud, K. (Karen); Slump, E. (Erika); J.T. van Dissel (Jaap)

    2017-01-01

    textabstractLatent tuberculosis infection (LTBI) screening and preventive treatment is one of the components of the World Health Organization (WHO) End TB strategy, and particularly relevant for low tuberculosis (TB) incidence countries, i.e. less than 100 TB cases per million population. The

  17. Epstein-Barr Virus: The Path from Latent to Productive Infection.

    Science.gov (United States)

    Chiu, Ya-Fang; Sugden, Bill

    2016-09-29

    The intrinsic properties of different viruses have driven their study. For example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. Epstein-Barr virus, another herpesvirus, has two properties that have driven its study: It causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. Here, we review our understanding of the path Epstein-Barr virus follows to move from a latent infection to and through its productive cycle. We use information from human infections to provide a framework for describing studies in cell culture and, where possible, the molecular resolutions from these studies. We also pose questions whose answers we think are pivotal to understanding this path, and we provide answers where we can.

  18. Screening for latent tuberculous infection in people living with HIV infection in Auckland, New Zealand.

    Science.gov (United States)

    Gow, N; Briggs, S; Nisbet, M

    2017-09-01

    New Zealand, which has a low incidence of tuberculosis (TB), has historically taken a risk-based approach to screening for latent tuberculous infection (LTBI) in adult people living with the human immunodeficiency virus infection (PLHIV). To evaluate LTBI screening, treatment and outcomes in an adult PLHIV population. This was a retrospective clinical record review of an initial cohort of adult PLHIV attending the Auckland City Hospital HIV clinic in 2011, and a second cohort of adult PLHIV newly attending the clinic in 2014. We analysed high-risk (born in or acquiring HIV in a high TB incidence country) and low-risk patients using descriptive statistical methods. Of the 752 patients from the initial cohort, 416 (55%) had documentation of LTBI screening, which was positive in 74 (10%): 19/461 (4%) low-risk and 55/291 (19%) high-risk patients. LTBI treatment was received in 13 low-risk and 44 high-risk patients. Of 73 patients in the second cohort, 68 (93%) were screened. LTBI screening was incomplete in our clinic, but improved between 2011 and 2014. A significant number of patients with LTBI did not originate from a high TB incidence country.

  19. Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1

    Science.gov (United States)

    Piret, Jocelyne; Lamontagne, Julie; Désormeaux, André; Bergeron, Michel G.

    2001-01-01

    The influence of sodium lauryl sulfate (SLS) on the efficacies of gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous lesions and on the establishment and reactivation of latent virus has been evaluated in a murine model of orofacial infection. Topical treatments were given twice daily for 3 days and were initiated at 6, 24, and 48 h after virus inoculation. The gel formulation that contained both 3% foscarnet and 5% SLS and that was administered within 48 h postinfection reduced the rate of development of herpetic skin lesions. This formulation also significantly decreased the viral content in skin tissues and in ipsilateral trigeminal ganglia when it was given within 24 and 6 h postinfection, respectively. A lower level of efficacy was observed for the gel formulation containing 3% foscarnet alone. Of prime interest, the gel formulation containing 5% SLS reduced significantly the mortality rate among mice in a zosteriform model of infection. Both formulations of foscarnet had no effect on the mean titers of reactivated virus in explant cultures of ipsilateral and contralateral trigeminal ganglia from latently infected mice. The use of a gel formulation containing combinations of foscarnet and SLS could represent an attractive approach for the treatment of herpetic mucocutaneous infections. PMID:11257012

  20. Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: A latent-class analysis.

    Directory of Open Access Journals (Sweden)

    Tan N Doan

    Full Text Available Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST and interferon-gamma release assays (IGRAs for LTBI diagnosis in various patient populations using Bayesian latent class modelling.Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85% and 52% (50-53%, respectively. The specificity of QFT-GIT was 97% (96-97% in non-BCG-vaccinated and 93% (92-94% in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100% and 79% (76-82%, respectively. T-SPOT.TB has comparable specificity (97% for both tests and better sensitivity (68% versus 52% than QFT-GIT in immune-competent adults

  1. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Xiaozhen Liang

    2009-11-01

    Full Text Available Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68 gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners that do not directly participate in virus replication, but rather facilitate virus

  2. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Science.gov (United States)

    Liang, Xiaozhen; Collins, Christopher M; Mendel, Justin B; Iwakoshi, Neal N; Speck, Samuel H

    2009-11-01

    Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68) gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency) account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners) that do not directly participate in virus replication, but rather facilitate virus reactivation by

  3. Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons.

    Science.gov (United States)

    Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Altice, Frederick L

    2014-01-10

    Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia's largest prison. From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other potential confounding factors

  4. Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent?

    Science.gov (United States)

    Rothel, James S; Andersen, Peter

    2005-12-01

    Tuberculosis is responsible for more then 2 million deaths worldwide each year and vies with HIV as the world's most fatal infectious disease. In many developing countries, attempts to control the spread of infection rely solely on identification and treatment of those with active disease, ignoring subclinical infection. However, in developed countries, large efforts are also expended to identify and give prophylactic drugs to people with latent tuberculosis infection. Until recently, the 100-year-old tuberculin skin test (Mantoux) has been the only available diagnostic test for latent tuberculosis infection, despite its many well-known limitations. Advances in scientific knowledge have led to the development of tests for tuberculosis that measure the production of interferon-gamma by T-cells stimulated in vitro with Mycobacterium tuberculosis-specific antigens. These interferon-gamma tests are highly specific and unaffected by prior Bacille Calmette-Guérin vaccination or immune reactivity to most atypical mycobacteria. They are more sensitive than the tuberculin skin test in detecting people with active tuberculosis, and their results correlate more closely with M. tuberculosis exposure risk factors than the tuberculin skin test in people likely to have latent tuberculosis infection. Science has caught up with one of the oldest diagnostic tests still in use worldwide, and the adoption of new, tuberculosis-specific interferon-gamma-based tests should move us one step closer to better control of this insidious pathogen.

  5. Characterization of a Latent Virus-Like Infection of Symbiotic Zooxanthellae▿

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B.; Wilson, William H.

    2007-01-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms. PMID:17351090

  6. Characterization of a latent virus-like infection of symbiotic zooxanthellae.

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B; Wilson, William H

    2007-05-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms.

  7. New, previously unreported correlations between latent Toxoplasma gondii infection and excessive ethanol consumption.

    Science.gov (United States)

    Samojłowicz, Dorota; Borowska-Solonynko, Aleksandra; Kruczyk, Marcin

    2017-11-01

    A number of world literature reports indicate that a latent Toxoplasma gondii infection leads to development of central nervous system disorders, which in turn may lead to altered behavior in the affected individuals. T. gondii infection has been observed to play the greatest role in drivers, suicides, and psychiatric patients. Studies conducted for this manuscript involve a different, never before really reported correlation between latent T. gondii infection and ethanol abuse. A total of 538 decedents with a known cause of death were included in the study. These individuals were divided into three groups: the risky behavior group, inconclusively risky behavior group, and control group. The criterion for this division was the likely effect of the individual's behavior on the mechanism and cause of his/her death. The material used for analyses were blood samples collected during routine medico-legal examinations in these cases. The blood samples were used to measure anti-T. gondii IgG antibodies with an enzyme-linked immunosorbent assay (ELISA). Moreover, the following data were recorded for each decedent: sex, age, circumstances of death, cause of death, time from death to autopsy, and (if provided) substance abuse status (alcohol, illicit drugs). In those cases where blood alcohol level or toxicology tests were requested by the Prosecutor's Office, their results were also included in our analysis. Test results demonstrated a strong correlation between latent T. gondii infection and engaging in risky behaviors leading to death. Moreover, analyses demonstrated a positive correlation between the presence of anti-T. gondii IgG antibodies and psychoactive substance (especially ethanol) abuse, however, the causal relationship remains unclear. Due to the fact that alcohol abuse constitutes a significant social problem, searching for eliminable risk factors for addiction is extremely important. Our analyses provided new important information on the possible effects of

  8. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  9. Latent tuberculosis infection screening prior to biological treatment in Tunisian patients.

    Science.gov (United States)

    Slouma, Marwa; Mahmoud, Ines; Saidane, Olfa; Bouden, Selma; Abdelmoula, Leila

    2017-10-01

    The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

    DEFF Research Database (Denmark)

    Reinert, Line; Harder, Louis Andreas; Holm, Christian

    2012-01-01

    Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation......, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...

  11. Latent Tuberculosis Infection in an Urban Cohort: Screening and Treatment for Latent TB in an Urban Setting

    Science.gov (United States)

    Morano, Jamie P.; Walton, Mary R.; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

    2013-01-01

    Background Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Methods Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2523 completed tuberculin skin tests (TST’s) resulted in 357 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes 1) initiation of isoniazid preventative therapy (IPT) and 2) completion of 9-months IPT. Results Of 357 new LTBIs, 86.3% (n=308) completed screening CXRs: 90.3% (n=278) were normal and 0.3% (n=1) with active tuberculosis. Of those completing CXR screening, 44.0% (n=135) agreed to IPT: 69.6% (n=94) selected DOT, and 30.4% (n=41) selected SAT. Initiating IPT was correlated with undocumented status (AOR=3.43; pmodels for LTBI treatment resulted in similar outcomes, yet outcomes were hampered by differential measurement bias between DOT and SAT participants. PMID:23728822

  12. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans.

    Science.gov (United States)

    Efstathiou, S; Minson, A C; Field, H J; Anderson, J R; Wildy, P

    1986-02-01

    Herpes simplex virus-specific DNA sequences have been detected by Southern hybridization analysis in both central and peripheral nervous system tissues of latently infected mice. We have detected virus-specific sequences corresponding to the junction fragment but not the genomic termini, an observation first made by Rock and Fraser (Nature [London] 302:523-525, 1983). This "endless" herpes simplex virus DNA is both qualitatively and quantitatively stable in mouse neural tissue analyzed over a 4-month period. In addition, examination of DNA extracted from human trigeminal ganglia has shown herpes simplex virus DNA to be present in an "endless" form similar to that found in the mouse model system. Further restriction enzyme analysis of latently infected mouse brainstem and human trigeminal DNA has shown that this "endless" herpes simplex virus DNA is present in all four isomeric configurations.

  13. Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis

    OpenAIRE

    Zenner, D.; Beer, N.; Harris, R. J.; Lipman, M. C.; Stagg, H. R.; van der Werf, M. J.

    2017-01-01

    Background: Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI. Purpose: To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children. Data Sources: PubMed, Embase, and Web of Science from indexing ...

  14. Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection

    OpenAIRE

    Claudia C. Dobler; Sinthia Bosnic-Anticevich; Carol L. Armour

    2018-01-01

    The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explain...

  15. National policies on the management of latent tuberculosis infection: review of 98 countries

    Science.gov (United States)

    Jagger, Ann; Reiter-karam, Silke; Getahun, Haileyesus

    2018-01-01

    Abstract Objective To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. Methods We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. Findings We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries’ policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. Conclusion Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies. PMID:29531416

  16. The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure.

    Science.gov (United States)

    Ranganath, Nischal; Sandstrom, Teslin S; Burke Schinkel, Stephanie C; Côté, Sandra C; Angel, Jonathan B

    2018-02-14

    Cells latently infected with human immunodeficiency virus (HIV) evade immune- and drug-mediated clearance. These cells harbor intracellular signaling defects, including impairment of the antiviral type I interferon response. Such defects have also been observed in several cancers and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate cells latently infected with HIV-1, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in cell lines latently infected with HIV-1. Following this, a reduction in HIV-1 DNA and inducible HIV-1 replication was observed following MG1 infection of latently infected, resting CD4+ T cells generated using an in vitro model of latency. Last, MG1 infection resulted in a reduction in HIV-1 DNA and inducible HIV-1 replication in memory CD4+ T cells isolated from effectively treated, HIV-1-infected individuals. Our results therefore highlight a novel approach to eliminate the latent HIV-1 reservoir. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    International Nuclear Information System (INIS)

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-01-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation

  18. The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling.

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    Rein M G J Houben

    2016-10-01

    Full Text Available The existing estimate of the global burden of latent TB infection (LTBI as "one-third" of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI.We constructed trends in annual risk in infection (ARI for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011 and indirect estimates of ARI calculated from World Health Organisation (WHO estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y, and recently infected with isoniazid (INH-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%-26.4%, amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%-0.9% of the global population, amounting to 55.5 (95% UI: 48.2-63.8 million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%-11.8% was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI

  19. Latent potyvirus infections in Crocus sativus artwrightianus: an underestimated problem in saffron?

    Directory of Open Access Journals (Sweden)

    Maria GRILLI CAIOLA

    2011-09-01

    Full Text Available Normal 0 14 false false false IT X-NONE X-NONE MicrosoftInternetExplorer4 In over two decades, while studying saffron reproductive biology, we frequently found ultrastructural alterations typical of potyvirus infection in stigmas, styles and leaves of Crocus sativus (saffron and C. cartwrightianus (wild and ornamental species, a putative ancestor of saffron from different provenance. This suggests that these viruses are widely diffused in cultivated Crocus spp., possibly causing latent infections. The few data found in literature, while highlighting the general lack of attention given by plant virologists to Crocus spp., nevertheless confi rm that potyviruses, particularly Bean yellow mosaic virus (BYMV, can cause asymptomatic infections in these host species. The reasons and possible implications of widely distributed potyvirus latent infections in Crocus spp. are reported and discussed, with the aim of increasing general awareness of these viruses, and of encouraging sanitary selection programs focused on saffron, that could improve the quantity and quality of yields of the most expensive spice commodity grown.

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

    Directory of Open Access Journals (Sweden)

    Stefan Czemmel

    Full Text Available Some pathogenic species of the Botryosphaeriaceae have a latent phase, colonizing woody tissues while perennial hosts show no apparent symptoms until conditions for disease development become favorable. Detection of these pathogens is often limited to the later pathogenic phase. The latent phase is poorly characterized, despite the need for non-destructive detection tools and effective quarantine strategies, which would benefit from identification of host-based markers in leaves. Neofusicoccum parvum infects the wood of grapevines and other horticultural crops, killing the fruit-bearing shoots. We used light microscopy and high-resolution computed tomography (HRCT to examine the spatio-temporal relationship between pathogen colonization and anatomical changes in stem sections. To identify differentially-expressed grape genes, leaves from inoculated and non-inoculated plants were examined using RNA-Seq. The latent phase occurred between 0 and 1.5 months post-inoculation (MPI, during which time the pathogen did not spread significantly beyond the inoculation site nor were there differences in lesion lengths between inoculated and non-inoculated plants. The pathogenic phase occurred between 1.5 and 2 MPI, when recovery beyond the inoculation site increased and lesion lengths of inoculated plants tripled. By 2 MPI, inoculated plants also had decreased starch content in xylem fibers and rays, and increased levels of gel-occluded xylem vessels, the latter of which HRCT revealed at a higher frequency than microscopy. RNA-Seq and screening of 21 grape expression datasets identified 20 candidate genes that were transcriptionally-activated by infection during the latent phase, and confirmed that the four best candidates (galactinol synthase, abscisic acid-induced wheat plasma membrane polypeptide-19 ortholog, embryonic cell protein 63, BURP domain-containing protein were not affected by a range of common foliar and wood pathogens or abiotic stresses

  1. Acute and latent infection by bovine herpesvirus type 2 in a guinea pig model.

    Science.gov (United States)

    Torres, Fabrício Dias; Cargnelutti, Juliana Felipetto; Masuda, Eduardo Kenji; Weiblen, Rudi; Flores, Eduardo Furtado

    2010-02-01

    Bovine herpetic mammillits is a self-limiting cutaneous disease of the udder and teats of cows associated with bovine herpesvirus 2 (BoHV-2) whose pathogenesis is poorly understood. This article describes the use of guinea pigs (Cavia porcellus) to study the pathogenesis of BoHV-2 infection. Twelve weanling female guinea pigs inoculated subcutaneously with BoHV-2 in the genitalia and teats developed local hyperemia, edema, vesicles, ulcers and scabs. Infectious virus was recovered between days 3 and 7 post-infection (pi) from the genital area (9/12) and teats (1/12); and all inoculated animals seroconverted (virus-neutralizing titers of 16-128). Histological examination of lesions revealed lymphoplasmacytic perivascular infiltrates and intranuclear inclusion bodies in keratinocytes. PCR examination of tissues collected at day 35 pi detected latent viral DNA predominantly in lumbosacral spinal segments. In another experiment, eight females inoculated with BoHV-2 in the genitalia and treated with dexamethasone (Dx) at day 35 pi developed mild to moderate local signs, yet no virus could be recovered from lesions. PCR examination of spinal segments from these animals confirmed the presence of latent viral DNA. These results demonstrate that guinea pigs are susceptible to BoHV-2 infection and therefore may be used to study selected aspects of BoHV-2 biology.

  2. Latent Tuberculosis Infection and Associated Factors among Health Care Workers in Kigali, Rwanda.

    Directory of Open Access Journals (Sweden)

    Claude Rutanga

    Full Text Available Data are limited regarding tuberculosis (TB and latent TB infection prevalence in Rwandan health facilities.We conducted a cross-sectional survey among healthcare workers (HCWs in Kigali during 2010. We purposively selected the public referral hospital, both district hospitals, and randomly selected 7 of 17 health centers. School workers (SWs from the nearest willing public schools served as a local reference group. We tested for latent TB infection (LTBI using tuberculin skin testing (TST and asked about past TB disease. We assessed risk of LTBI and past history of TB disease associated with hospital employment. Among HCWs, we assessed risk associated with facility type (district hospital, referral hospital, health center, work setting (inpatient, outpatient, and occupation.Age, gender, and HIV status was similar between the enrolled 1,131 HCWs and 381 SWs. LTBI was more prevalent among HCWs (62% than SWs (39%. Adjusted odds of a positive TST result were 2.71 (95% CI 2.01-3.67 times greater among HCWs than SWs. Among HCWs, there was no detectable difference between prevalence of LTBI according to facility type, work setting, or occupation.HCWs are at greater risk of LTBI, regardless of facility type, work setting, or occupation. The current status of TB infection control practices should be evaluated in the entire workforce in all Rwandan healthcare facilities.

  3. Experimental canine distemper infection as a means of demonstrating latent effects of subacute lead intoxication

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J.; McLeod, S.

    1976-01-01

    Observations on the response of the body to experimental infection with distemper virus in dogs previously dosed subacutely with lead have demonstrated a latent effect of lead on several body systems. Effects which indicated a relationship to earlier treatment with lead included evidence for stimulation of haemoglobin synthesis, changes to red blood cells resulting in increased destruction, increased vulnerability of the parenchymatous cells of the liver to damage, reduction in the weight of the skeleton and thyroid, an increase in weight of the thymus and brain and histopathological changes in the thymus. 21 references, 2 figures, 1 table.

  4. Thermostability of IFN-γ and IP-10 release assays for latent infection with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Blauenfeldt, Thomas; Wagner, Dirk; Aabye, Martine Grosos

    2016-01-01

    accuracy of IP-10 release assay and IGRAs. RESULTS: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0......INTRODUCTION: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher...

  5. The prevalence of latent Mycobacterium tuberculosis infection based on an interferon-γ release assay

    DEFF Research Database (Denmark)

    Jensen, Andreas V.; Jensen, Lotte; Faurholt-Jepsen, Daniel

    2013-01-01

    Introduction:One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI....... The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute...

  6. PREDICTING THE RISK OF LATENT TUBERCULOUS INFECTION IN THOSE SERVING THEIR SENTENCES IN THE PENITENTIARY SYSTEM

    Directory of Open Access Journals (Sweden)

    V. S. Borovitsky

    2018-01-01

    Full Text Available The objective of the study: to assess the prevalence of latent tuberculous infection (LTI and risk of its development in the inmates servicing their sentence in a penal colony of the Federal Penitentiary System, using the tools of statistics analysisSubjects and Methods. 232 persons in the age from 18 to 67 (27; 225-35 years old were examined Results. Exposure to a tuberculosis case in the past and duration of imprisonment are statistically confident risk factors of developing LTI The use of statistic tools allows predicting the chances of LTI 

  7. Tratamento da tuberculose de infecção latente: As recomendações actuais Latent tuberculosis infection treatment: Current recommendations

    Directory of Open Access Journals (Sweden)

    R Duarte

    2010-09-01

    Full Text Available O diagnóstico e tratamento da infecção latente por Mycobacterium tuberculosis reduz significativamente o risco de desenvolvimento de tuberculose activa e a transmissão da doença na comunidade. O rastreio da tuberculose infecção latente deve passar pela exclusão de doença activa (inquérito de sintomas e radiografia pulmonar e avaliação da resposta imunológica ao M. tuberculosis através dos testes actualmente ao dispor, como o teste tuberculínico e os testes IGRA (interferon-gamma release assay. A escolha do esquema de tratamento deve ter em linha de conta a eficácia, a adesão e os efeitos colaterais associados ao mesmo Este documento actualiza as recomendações sobre tratamento da tuberculose infecção latente. São apresentadas indicações sobre quem deve ser rastreado e revistos os esquemas de tratamento.Diagnosis and treatment of latent infection with Mycobacterium tuberculosis (LTBI, significantly reduces the risk of developing active tuberculosis and the transmission of the disease in the community. LTBI screening must pass by the exclusion of active disease (symptoms enquiry and chest radiography and assessment of immune response to Mycobacterium tuberculosis testing with the tests currently available - tuberculin skin test and interferon-gamma release assay (IGRA. The choice of treatment must take into account the efficacy and side effects associated with the same. This document provides updated recommendations on latent tuberculosis infection treatment. Topics covered include whom to test for TB and reviewed LTBI treatment regimens.

  8. Latent and subclinical tuberculosis in HIV infected patients: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kall Meaghan M

    2012-05-01

    Full Text Available Abstract Background HIV and tuberculosis (TB are commonly associated. Identifying latent and asymptomatic tuberculosis infection in HIV-positive patients is important in preventing death and morbidity associated with active TB. Methods Cross-sectional study of one time use of an interferon-gamma release assay (T-SPOT.TB - immunospot to detect tuberculosis infection in patients in a UK inner city HIV clinic with a large sub-Saharan population. Results 542 patient samples from 520 patients who disclosed their symptoms of TB were tested. Median follow-up was 35 months (range 27-69. More than half (55% originated from countries with medium or high tuberculosis burden and 57% were women. Antiretroviral therapy was used by 67%; median CD4 count at test was 458 cells/μl. A negative test was found in 452 samples and an indeterminate results in 40 (7.4% but neither were associated with a low CD4 count. A positive test was found in 10% (50/502 individuals. All patients with positive tests were referred to the TB specialist, 47 (94% had a chest radiograph and 46 (92% attended the TB clinic. Two had culture-positive TB and a third individual with features of active TB was treated. 40 started and 38 completed preventive treatment. One patient who completed preventive treatment with isoniazid monotherapy subsequently developed isoniazid-resistant pulmonary tuberculosis. No patient with a negative test has developed TB. Conclusions We found an overall prevalence of latent TB infection of 10% through screening for TB in those with HIV infection and without symptoms, and a further 1% with active disease, a yield greater than typically found in contact tracing. Acceptability of preventive treatment was high with 85% of those with latent TB infection eventually completing their TB chemotherapy regimens. IGRA-based TB screening among HIV-infected individuals was feasible in the clinical setting and assisted with appropriate management (including preventive

  9. The interrelation between intestinal parasites and latent TB infections among newly resettled refugees in Texas.

    Science.gov (United States)

    Board, Amy R; Suzuki, Sumihiro

    2016-01-01

    Previous research has documented that parasite infection may increase vulnerability to TB among certain at risk populations. The purpose of this study was to identify whether an association exists between latent tuberculosis infection (LTBI) and intestinal parasite infection among newly resettled refugees in Texas while controlling for additional effects of region of origin, age and sex. Data for all refugees screened for both TB and intestinal parasites between January 2010 and mid-October 2013 were obtained from the Texas Refugee Health Screening Program and were analyzed using logistic regression. A total of 9860 refugees were included. In multivariable logistic regression analysis, pathogenic and non-pathogenic intestinal parasite infections yielded statistically significant reduced odds of LTBI. However, when individual parasite species were analyzed, hookworm infection indicated statistically significant increased odds of LTBI (OR 1.674, CI: 1.126-2.488). A positive association exists between hookworm infection and LTBI in newly arrived refugees to Texas. More research is needed to assess the nature and extent of these associations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  11. Detection of Colletotrichum acutatum Latent Infections in Strawberry Petioles and Leaves

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    Nataša Duduk

    2008-01-01

    Full Text Available Colletotrichum acutatum is the most significant agent of anthracnose strawberry fruit rot. Besides being a necrotrophic pest, it can spend a part of its life cycle as an epiphyte, in a form of latent infection. The presence of the fungi on symptomless plant tissue is considered one of the main ways of distribution of this economically harmful pathogen in the world. Investigation of latent C. acutatum infection was carried out on artificially inoculated strawberries. The initiation of fungi sporulation on symptomless petioles and leaves was carried out by exposing them to the herbicide paraquat (0.25% and low temperatures, which caused plant tissue decay in different ways. Surface sterilization with 0.5% NaOCl precedes the exposure of plant material to paraquat. The freezing procedure was carried out by exposure of plant material to the temperature of -20°C for 2h. After the freezing, one group was rinsed in Tween 20 (18 μl/l, and another group underwent surface sterilization in 0.0525% NaOCl with an addition of Tween 20 (18 μl/l. After 6 days of incubation, the appearance of acervuli and conidia was detected in 93.33 to 100% plant parts exposed to paraquat treatment and freezing procedure. In inoculated parts which were not exposed to herbicides or low temperatures, the presence of acervuli was detected in 3.33% tested petioles and 6.67% leaves.

  12. Policy and practice of programmatic management of latent tuberculosis infection in The Netherlands

    Directory of Open Access Journals (Sweden)

    Gerard de Vries

    2017-05-01

    Full Text Available Latent tuberculosis infection (LTBI screening and preventive treatment is one of the components of the World Health Organization (WHO End TB strategy, and particularly relevant for low tuberculosis (TB incidence countries, i.e. less than 100TB cases per million population. The Netherlands is such a low-incidence country with traditionally a strong emphasis on programmatic management of LTBI, e.g. examining contacts of infectious TB patients by the public health services. Increasingly, curative services are involved in LTBI management of clinical risk groups. The country recently adopted a five-year strategic national plan recommending LTBI screening of high-risk migrants populations. A monitoring and evaluation system is already in place to measure programme performance and guide policy. Research on LTBI screening of migrants is on-going and results should inform future decisions in scaling-up this intervention. Several challenges remain for programmatic LTBI management, such as securing financial resources and the right professional cadre for implementation; availability of screening tests and drugs; collecting additional data for monitoring and evaluation, in line with the WHO indicators for LTBI programmatic management; developing cultural-sensitive and client-centred education for migrants; reducing patient costs for LTBI screening and preventive treatment; and assessing cost-effectiveness and impact on TB epidemiology. Keywords: Elimination, Latent tuberculosis infection, Prevention, Screening, Tuberculosis, Municipal Public Health Service

  13. Cost-effectiveness of post-landing latent tuberculosis infection control strategies in new migrants to Canada.

    Science.gov (United States)

    Campbell, Jonathon R; Johnston, James C; Sadatsafavi, Mohsen; Cook, Victoria J; Elwood, R Kevin; Marra, Fawziah

    2017-01-01

    The majority of tuberculosis in migrants to Canada occurs due to reactivation of latent TB infection. Risk of tuberculosis in those with latent tuberculosis infection can be significantly reduced with treatment. Presently, only 2.4% of new migrants are flagged for post-landing surveillance, which may include latent tuberculosis infection screening; no other migrants receive routine latent tuberculosis infection screening. To aid in reducing the tuberculosis burden in new migrants to Canada, we determined the cost-effectiveness of using different latent tuberculosis infection interventions in migrants under post-arrival surveillance and in all new migrants. A discrete event simulation model was developed that focused on a Canadian permanent resident cohort after arrival in Canada, utilizing a ten-year time horizon, healthcare system perspective, and 1.5% discount rate. Latent tuberculosis infection interventions were evaluated in the population under surveillance (N = 6100) and the total cohort (N = 260,600). In all evaluations, six different screening and treatment combinations were compared to the base case of tuberculin skin test screening followed by isoniazid treatment only in the population under surveillance. Quality adjusted life years, incident tuberculosis cases, and costs were recorded for each intervention and incremental cost-effectiveness ratios were calculated in relation to the base case. In the population under surveillance (N = 6100), using an interferon-gamma release assay followed by rifampin was dominant compared to the base case, preventing 4.90 cases of tuberculosis, a 4.9% reduction, adding 4.0 quality adjusted life years, and saving $353,013 over the ensuing ten-years. Latent tuberculosis infection screening in the total population (N = 260,600) was not cost-effective when compared to the base case, however could potentially prevent 21.8% of incident tuberculosis cases. Screening new migrants under surveillance with an interferon

  14. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

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    Elena Ufimtseva

    2015-01-01

    Full Text Available Tuberculosis (TB is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

  15. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

    Science.gov (United States)

    2015-01-01

    Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

  16. Prevalence and factors associated with latent tuberculosis infection in an indigenous population in the Brazilian Amazon.

    Science.gov (United States)

    Malacarne, Jocieli; Rios, Diana Patricia Giraldo; Silva, Cosme Marcelo Furtado Passos da; Braga, José Ueleres; Camacho, Luiz Antonio Bastos; Basta, Paulo Cesar

    2016-01-01

    Recent studies have shown a high incidence and prevalence of latent tuberculosis infection (LTBI) in indigenous populations around the World. We aimed to estimate the prevalence and annual risk of infection (ARI) as well as to identify factors associated with LTBI in an indigenous population from the Brazilian Amazon. We conducted a cross-sectional study in 2011. We performed tuberculin skin tests (TSTs), smears and cultures of sputum samples, and chest radiographs for individuals who reported cough for two or more weeks. Associations between LTBI (TST ≥5mm) and socio-demographic, clinical, and epidemiological characteristics were investigated using Poisson regression with robust variance. Prevalence ratio (PR) was used as the measure of association. We examined 263 individuals. The prevalence of LTBI was 40.3%, and the ARI was 2.4%. Age ≥15 years [PR=5.5; 95% confidence interval (CI): 3.5-8.6], contact with tuberculosis (TB) patients (PR=3.8; 95% CI: 1.2-11.9), previous TB history (PR=1.4; 95% CI: 1.2-1.7), and presence of Bacillus Calmette-Guérin (BCG) scar (PR=1.9, 95% CI: 1.2-2.9) were associated with LTBI. Although some adults may have been infected years prior, the high prevalence of infection and its strong association with age ≥15 years, history of TB, and recent contact with TB patients suggest that the TB transmission risk is high in the study area.

  17. Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

    Science.gov (United States)

    Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

    2017-07-01

    Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

  18. Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist.

    Science.gov (United States)

    Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

    2009-01-01

    The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants were university students diagnosed with LTBI. The authors conducted a retrospective review of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken, characteristics of completers versus noncompleters, average time to treatment completion, and reported adverse drug events. The 9-month completion rate was 59%, and the 6-month completion rate was 67%. Among those not completing treatment, 15.2% experienced fatigue and 2.2% experienced a rash (p=.04 and p=.03, respectively). LTBI clinics are a unique niche for community pharmacies and can provide individualized patient care to ensure LTBI treatment adherence, monitoring for disease progression, and safety of INH.

  19. Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection.

    Science.gov (United States)

    Ene, L; Marcotte, T D; Umlauf, A; Grancea, C; Temereanca, A; Bharti, A; Achim, C L; Letendre, S; Ruta, S M

    2016-10-15

    We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24years, 48.2% males) with chronic HIV infection (HIV+) since childhood and 51 HIV seronegative (HIV-) participants were included. HIV+ individuals had good current immunological status (median CD4: 479 cells/μl) despite a low CD4 nadir (median: 93 cells/μl). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV- with and without Toxo were not significantly different (p=0.17). However, we observed an increasing trend (pToxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models.

    Directory of Open Access Journals (Sweden)

    Wirichada Pan-ngum

    Full Text Available Accuracy of rapid diagnostic tests for dengue infection has been repeatedly estimated by comparing those tests with reference assays. We hypothesized that those estimates might be inaccurate if the accuracy of the reference assays is not perfect. Here, we investigated this using statistical modeling.Data from a cohort study of 549 patients suspected of dengue infection presenting at Colombo North Teaching Hospital, Ragama, Sri Lanka, that described the application of our reference assay (a combination of Dengue IgM antibody capture ELISA and IgG antibody capture ELISA and of three rapid diagnostic tests (Panbio NS1 antigen, IgM antibody and IgG antibody rapid immunochromatographic cassette tests were re-evaluated using bayesian latent class models (LCMs. The estimated sensitivity and specificity of the reference assay were 62.0% and 99.6%, respectively. Prevalence of dengue infection (24.3%, and sensitivities and specificities of the Panbio NS1 (45.9% and 97.9%, IgM (54.5% and 95.5% and IgG (62.1% and 84.5% estimated by bayesian LCMs were significantly different from those estimated by assuming that the reference assay was perfect. Sensitivity, specificity, PPV and NPV for a combination of NS1, IgM and IgG cassette tests on admission samples were 87.0%, 82.8%, 62.0% and 95.2%, respectively.Our reference assay is an imperfect gold standard. In our setting, the combination of NS1, IgM and IgG rapid diagnostic tests could be used on admission to rule out dengue infection with a high level of accuracy (NPV 95.2%. Further evaluation of rapid diagnostic tests for dengue infection should include the use of appropriate statistical models.

  1. CT screening before treatment of latent tuberculous infection for the diagnosis of clinical TB among contacts

    International Nuclear Information System (INIS)

    Yoshiyama, Takashi; Ogata, Hideo

    2008-01-01

    The objective of this study was to evaluate the value of CT scan for the detection of tuberculous diseases among persons who are suspected to be infected at the contact examination. The settings of this study was to Fukujuji Hospital, Japan. Retrospective review of the medical records of 22 persons who were normal with plain chest X-ray at an outbreak at a private school, with which total 46 tuberculosis (TB) cases and 93 infected persons were detected by either symptomatic visits or contact examinations done mainly at public health centers. Among the 44 persons who visited Fukujuji Hospital, 4 persons were symptomatic visits, 3 persons were detected as TB cases by the contact examination at public health centers and 3 persons visited Fukujuji Hospital for the purpose of contact examination before examinations at the public health centers. Eight of these 10 persons were with abnormal chest plain X-ray findings and the remaining two persons were normal with plain chest X-ray findings (group A). Among the 34 persons who were referred to Fukujuji Hospital from public health centers as the infected person without diseases, one person showed abnormal chest plain X-ray and 33 persons showed normal chest plain X-ray (group B). Group A persons were examined in June and Group B persons were examined in July. The 2 persons in the group A were with abnormal CT findings. They were not diagnosed as TB by the CT findings but followed up after sputum examinations. Both of them were diagnosed as TB by the positive TB culture. Among the 33 persons in the group B, 20 persons were tested with CT scan at the examination done before starting treatment of latent tuberuclous infection and six of these 20 persons were with abnormal findings and were judged as TB diseases. In the case of outbreak with many TB cases and infected persons, CT should be considered for the detection of TB cases among contacts. (author)

  2. Prognostic factors for tuberculosis development in children with latent tuberculous infection

    Directory of Open Access Journals (Sweden)

    N. V. Korneva

    2016-01-01

    Full Text Available Goal of the study: to detect specific immune response in children with latent tuberculous infection and define factors to forecast the development of the active disease in this group.Materials and methods. The changes in clinical, X-ray and immunological data were analyzed in 127 children when latent tuberculous infection was diagnosed and after 12 months of follow-up. The number of immunological tests was done for evaluation of humoral and cellular immunity in those suffering from latent tuberculous infection and active disease.Results. The obtained results showed high negative prognostic relevance of exposure to tuberculosis, concurrent disease, refusal to have preventive treatment and low efficiency of short-course preventive treatment, specific features of humoral and cellular immunity were defined which could be used as additional forecasting criteria for active tuberculosis development in children with latent tuberculous infection

  3. 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...

  4. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

    OpenAIRE

    Wu, Lawrence Shih-Hsin; Lee, Shih-Wei; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che; Weng, Julia Tzu-Ya

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs ...

  5. FISHing Out the Hidden Enemy: Advances in Detecting and Measuring Latent HIV-Infected Cells.

    Science.gov (United States)

    Prasad, Vinayaka R; Kalpana, Ganjam V

    2017-09-19

    The indomitable aspect of HIV-1 infection is not that HIV-1 proviral DNA is integrated into host DNA but that it can also turn itself off, remaining invisible to drug or immune surveillance. Thus, the goals of eradication include ways to precisely excise HIV-1 DNA or wake up the silent HIV-1 provirus and eliminate the infected cells thus identified. Methods to identify and fish out the latently infected cells or to delineate their characteristics are being rapidly developed. In 2016, Baxter et al. (A. E. Baxter, J. Niessl, R. Fromentin, J. Richard, F. Porichis, R. Charlebois, M. Massanella, N. Brassard, N. Alsahafi, G. G. Delgado, J. P. Routy, B. D. Walker, A. Finzi, N. Chomont, and D. E. Kaufmann, Cell Host Microbe 20:368-380, 2016, https://doi.org/10.1016/j.chom.2016.07.015) and Martrus et al. (G. Martrus, A. Niehrs, R. Cornelis, A. Rechtien, W. García-Beltran, M. Lütgehetmann, C. Hoffmann, and M. Altfeld, J Virol 90:9018-9028, 2016, https://doi.org/10.1128/JVI.01448-16) reported using the fluorescence in situ hybridization-flow cytometry technique to identify and quantify cells expressing HIV-1 RNA and Gag protein, as well as bearing unique cell surface markers. In a recent article in mBio , Grau-Expósito et al. (J. Grau-Expósito, C. Serra-Peinado, L. Miguel, J. Navarro, A. Curran, J. Burgos, I. Ocaña, E. Ribera, A. Torrella, B. Planas, R. Badía, J. Castellví, V. Falcó, M. Crespo, and M. J. Buzon, mBio 8:e00876-17, 2017, https://doi.org/10.1128/mBio.00876-17) reported a similar method that they claim to be more sensitive. With these methods, researchers are one step closer to measuring latent reservoirs and eliminating critical barriers to HIV eradication. Copyright © 2017 Prasad and Kalpana.

  6. FISHing Out the Hidden Enemy: Advances in Detecting and Measuring Latent HIV-Infected Cells

    Directory of Open Access Journals (Sweden)

    Vinayaka R. Prasad

    2017-09-01

    Full Text Available The indomitable aspect of HIV-1 infection is not that HIV-1 proviral DNA is integrated into host DNA but that it can also turn itself off, remaining invisible to drug or immune surveillance. Thus, the goals of eradication include ways to precisely excise HIV-1 DNA or wake up the silent HIV-1 provirus and eliminate the infected cells thus identified. Methods to identify and fish out the latently infected cells or to delineate their characteristics are being rapidly developed. In 2016, Baxter et al. (A. E. Baxter, J. Niessl, R. Fromentin, J. Richard, F. Porichis, R. Charlebois, M. Massanella, N. Brassard, N. Alsahafi, G. G. Delgado, J. P. Routy, B. D. Walker, A. Finzi, N. Chomont, and D. E. Kaufmann, Cell Host Microbe 20:368–380, 2016, https://doi.org/10.1016/j.chom.2016.07.015 and Martrus et al. (G. Martrus, A. Niehrs, R. Cornelis, A. Rechtien, W. García-Beltran, M. Lutgehetmann, C. Hoffmann, and M. Altfeld, J Virol 90:9018–9028, 2016, https://doi.org/10.1128/JVI.01448-16 reported using the fluorescence in situ hybridization-flow cytometry technique to identify and quantify cells expressing HIV-1 RNA and Gag protein, as well as bearing unique cell surface markers. In a recent article in mBio, Grau-Expíósito et al. (J. Grau-Expíóósito, C. Serra-Peinado, L. Miguel, J. Navarro, A. Curran, J. Burgos, I. Ocaíóóña, E. Ribera, A. Torrella, B. Planas, R. Badíóóñía, J. Castellvíóóñíí, V. Falcíóóñííó, M. Crespo, and M. J. Buzon, mBio 8:e00876-17, 2017, https://doi.org/10.1128/mBio.00876-17 reported a similar method that they claim to be more sensitive. With these methods, researchers are one step closer to measuring latent reservoirs and eliminating critical barriers to HIV eradication.

  7. Single-Cell RNA-Seq Reveals Transcriptional Heterogeneity in Latent and Reactivated HIV-Infected Cells.

    Science.gov (United States)

    Golumbeanu, Monica; Cristinelli, Sara; Rato, Sylvie; Munoz, Miguel; Cavassini, Matthias; Beerenwinkel, Niko; Ciuffi, Angela

    2018-04-24

    Despite effective treatment, HIV can persist in latent reservoirs, which represent a major obstacle toward HIV eradication. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of HIV-infected cells. Here, we used a primary model of HIV latency and single-cell RNA sequencing to characterize transcriptional heterogeneity during HIV latency and reactivation. Our analysis identified transcriptional programs leading to successful reactivation of HIV expression. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Patterns of Brucellosis Infection Symptoms in Azerbaijan: A Latent Class Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Rita Ismayilova

    2014-01-01

    Full Text Available Brucellosis infection is a multisystem disease, with a broad spectrum of symptoms. We investigated the existence of clusters of infected patients according to their clinical presentation. Using national surveillance data from the Electronic-Integrated Disease Surveillance System, we applied a latent class cluster (LCC analysis on symptoms to determine clusters of brucellosis cases. A total of 454 cases reported between July 2011 and July 2013 were analyzed. LCC identified a two-cluster model and the Vuong-Lo-Mendell-Rubin likelihood ratio supported the cluster model. Brucellosis cases in the second cluster (19% reported higher percentages of poly-lymphadenopathy, hepatomegaly, arthritis, myositis, and neuritis and changes in liver function tests compared to cases of the first cluster. Patients in the second cluster had a severe brucellosis disease course and were associated with longer delay in seeking medical attention. Moreover, most of them were from Beylagan, a region focused on sheep and goat livestock production in south-central Azerbaijan. Patients in cluster 2 accounted for one-quarter of brucellosis cases and had a more severe clinical presentation. Delay in seeking medical care may explain severe illness. Future work needs to determine the factors that influence brucellosis case seeking and identify brucellosis species, particularly among cases from Beylagan.

  9. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

    Science.gov (United States)

    Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R; Sterling, Timothy R; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

    2015-12-01

    Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone. Copyright ©ERS 2015.

  10. Prevalence of Latent Mycobacterium Tuberculosis Infection (LTBI) in Saudi Arabia; Population based survey.

    Science.gov (United States)

    Balkhy, Hanan H; El Beltagy, Kamel; El-Saed, Aiman; Aljasir, Badr; Althaqafi, Abdulhakeem; Alothman, Adel F; Alshalaan, Mohammad; Al-Jahdali, Hamdan

    2017-07-01

    The annual risk of tuberculosis infection (ARTI) data in Saudi Arabia has not been updated since 1993. To estimate the prevalence of latent TB infection (LTBI) and ARTI in a population-based sample in Saudi Arabia using Tuberculin skin test (TST) and QuantiFERON TB Gold in tube (QFT-GIT) test. A population-based cross sectional study was conducted between July 2010 and March 2013. Participants were randomly selected from the population served by the primary healthcare centers of the Ministry of National Guard Health Affairs in Riyadh, Jeddah, Alhassa and Dammam, Saudi Arabia. A total of 1369 participants were included. The overall prevalence of LTBI was similar using TST and QFT-GIT (9.3% and 9.1% respectively, p=0.872) but stratified prevalence rates were variable in all sociodemographic groups except marital status. Additionally, the prevalence rates of LTBI using either test alone showed significant differences by several sociodemographic and behavioral characteristics. The overall ARTI was 0.36% using TST and 0.35% using QFT-GIT. We are reporting much lower estimates for the prevalence of LTBI and the ARTI in a population-based sample in Saudi Arabia relative to the data that have been used for more than two decades. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort.

    Science.gov (United States)

    Rafiei, Nastaran; Williams, Jackie; Mulley, William R; Trauer, James M; Jenkin, Grant A; Rogers, Benjamin A

    2018-04-16

    Tuberculosis (TB) is a serious opportunistic infection in renal transplant recipients associated with high mortality. Screening and treatment of latent Mycobacterium tuberculosis infection (LTBI) offers an opportunity to prevent subsequent active disease. We retrospectively reviewed the records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 to assess current screening practices, the risks for and burden of active TB. A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Three patients were diagnosed with active TB after renal transplant, resulting in an incidence of 82 per 100,000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (530 per 100,000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggests that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure. This article is protected by copyright. All rights reserved.

  12. High prevalence of latent tuberculosis infection among injection drug users in Tijuana, Mexico.

    Science.gov (United States)

    Garfein, R S; Lozada, R; Liu, L; Laniado-Laborin, R; Rodwell, T C; Deiss, R; Alvelais, J; Catanzaro, A; Chiles, P G; Strathdee, S A

    2009-05-01

    We studied prevalence and correlates of latent tuberculosis infection (LTBI) among injection drug users (IDUs) in Tijuana, Mexico, where tuberculosis (TB) is endemic. IDUs aged > or =18 years were recruited via respondent-driven sampling (RDS) and underwent standardized interviews, human immunodeficiency virus (HIV) antibody testing and LTBI screening using Quanti-FERON((R))-TB Gold In-Tube, a whole-blood interferon-gamma release assay (IGRA). LTBI prevalence was estimated and correlates were identified using RDS-weighted logistic regression. Of 1020 IDUs, 681 (67%) tested IGRA-positive and 44 (4%) tested HIV-positive. Mean age was 37 years, 88% were male and 98% were Mexican-born. IGRA positivity was associated with recruitment nearest the US border (aOR 1.64, 95%CI 1.09-2.48), increasing years of injection (aOR 1.20/5 years, 95%CI 1.07-1.34), and years lived in Tijuana (aOR 1.10/5 years, 95%CI 1.03-1.18). Speaking some English (aOR 0.38, 95%CI 0.25-0.57) and injecting most often at home in the past 6 months (aOR 0.68, 95%CI 0.45-0.99) were inversely associated with IGRA positivity. Increased LTBI prevalence among IDUs in Tijuana appears to be associated with greater drug involvement. Given the high risk for HIV infection among Tijuana's IDUs, interventions are urgently needed to prevent HIV infection and treat LTBI among IDUs before these epidemics collide.

  13. Host markers in Quantiferon supernatants differentiate active TB from latent TB infection: preliminary report

    Directory of Open Access Journals (Sweden)

    Walzl Gerhard

    2009-05-01

    Full Text Available Abstract Background Interferon gamma release assays, including the QuantiFERON® TB Gold In Tube (QFT have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI and active TB disease. Methods We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay. Results Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF soluble CD40 ligand (sCD40L, antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP-1β were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1β predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-α and IL-1α also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-α and sCD40L levels were higher in TB patients. Conclusion These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1β, VEGF, TGF-α or IL-1α in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.

  14. 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

  15. Dual skin tests with Mycobacterium avium sensitin and PPD to detect misdiagnosis of latent tuberculosis infection.

    Science.gov (United States)

    Larson, E M; O'Donnell, M; Chamblee, S; Horsburgh, C R; Marsh, B J; Moreland, J D; Johnson, L S; von Reyn, C Fordham

    2011-11-01

    A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

  16. Can Social History Variables Predict Prison Inmates’ Risk for Latent Tuberculosis Infection?

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    Tyler E. Weant

    2012-01-01

    Full Text Available Improved screening and treatment of latent tuberculosis infection (LTBI in correctional facilities may improve TB control. The Ohio Department of Rehabilitation and Correction (ODRC consists of 32 prisons. Inmates are screened upon entry to ODRC and yearly thereafter. The objective of the study was to determine if social history factors such as tobacco, alcohol, and drug use are significant predictors of LTBI and treatment outcomes. We reviewed the medical charts of inmates and randomly selected age-matched controls at one ODRC facility for 2009. We used a conditional logistic regression to assess associations between selected social history variables and LTBI diagnosis. Eighty-nine inmates with a history of LTBI and 88 controls were identified. No social history variable was a significant predictor of LTBI. Medical comorbidities such as asthma, rheumatoid arthritis, and hepatitis C were significantly higher in inmates with LTBI. 84% of inmates diagnosed with LTBI had either completed or were on treatment. Annual TB screening may not be cost-effective in all inmate populations. Identification of factors to help target screening populations at risk for TB is critical. Social history variables did not predict LTBI in our inmate population. Additional studies are needed to identify inmates for the targeted TB testing.

  17. Risk factors for treatment default in close contacts with latent tuberculous infection.

    Science.gov (United States)

    Fiske, C T; Yan, F-X; Hirsch-Moverman, Y; Sterling, T R; Reichler, M R

    2014-04-01

    1) To characterize risk factors for non-completion of latent tuberculous infection treatment (LTBIT), and 2) to assess the impact of LTBIT regimens on subsequent risk of tuberculosis (TB). Close contacts of adults aged ⩾15 years with pulmonary TB were prospectively enrolled in a multi-center study in the United States and Canada from January 2002 to December 2006. Close contacts of TB patients were screened and cross-matched with TB registries to identify those who developed active TB. Of 3238 contacts screened, 1714 (53%) were diagnosed with LTBI. Preventive treatment was recommended in 1371 (80%); 1147 (84%) initiated treatment, of whom 723 (63%) completed it. In multivariate analysis, study site, initial interview sites other than a home or health care setting and isoniazid preventive treatment (IPT) were significantly associated with non-completion of LTBIT. Fourteen TB cases were identified in contacts, all of whom initiated IPT: two TB cases among persons who received ⩾6 months of IPT (66 cases/100 000 person-years [py]), and nine among those who received 0-5 months (median 2 months) of IPT (792 cases/100 000 py, P risk of active TB.

  18. Methodological considerations for economic modelling of latent tuberculous infection screening in migrants.

    Science.gov (United States)

    Shedrawy, J; Siroka, A; Oxlade, O; Matteelli, A; Lönnroth, K

    2017-09-01

    Tuberculosis (TB) in migrants from endemic to low-incidence countries results mainly from the reactivation of latent tuberculous infection (LTBI). LTBI screening policies for migrants vary greatly between countries, and the evidence on the cost-effectiveness of the different approaches is weak and heterogeneous. The aim of this review was to assess the methodology used in published economic evaluations of LTBI screening among migrants to identify critical methodological options that must be considered when using modelling to determine value for money from different economic perspectives. Three electronic databases were searched and 10 articles were included. There was considerable variation across this small number of studies with regard to economic perspective, main outcomes, modelling technique, screening options and target populations considered, as well as in parameterisation of the epidemiological situation, test accuracy, efficacy, safety and programme performance. Only one study adopted a societal perspective; others adopted a health care or wider government perspective. Parameters representing the cascade of screening and treating LTBI varied widely, with some studies using highly aspirational scenarios. This review emphasises the need for a more harmonised approach for economic analysis, and better transparency in how policy options and economic perspectives influence methodological choices. Variability is justifiable for some parameters. However, sufficient data are available to standardise others. A societal perspective is ideal, but can be challenging due to limited data. Assumptions about programme performance should be based on empirical data or at least realistic assumptions. Results should be interpreted within specific contexts and policy options, with cautious generalisations.

  19. Prevalence of latent tuberculous infection among adults in the general population of Ca Mau, Viet Nam.

    Science.gov (United States)

    Marks, G B; Nhung, N V; Nguyen, T A; Hoa, N B; Khoa, T H; Son, N V; Phuong, N T B; Tin, D M; Ho, J; Fox, G J

    2018-03-01

    The study was conducted in a randomly selected sample of persons aged 15 years living in Ca Mau Province, southern Viet Nam. To estimate the prevalence of latent tuberculous infection (LTBI) in the general adult population of this province of Viet Nam. The secondary objective was to examine age and sex differences in prevalence. A cross-sectional survey was conducted in a cluster-random sample of the population. Clusters were subcommunes. The presence of LTBI was assessed using the QuantiFERON®-TB Gold In-Tube test system. QuantiFERON tests were performed among 1319 persons aged 15 years (77.7% of those selected). The overall prevalence of positive tests was 36.8% (95%CI 33.4-40.3). The prevalence of a positive test was lower in females than in males (31.0% vs. 44.7%, OR 0.57, 95%CI 0.45-0.72, P Viet Nam have evidence of LTBI. Although LTBI prevalence is higher in males, the sex difference is not as great as that for TB notification rates.

  20. Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection.

    Science.gov (United States)

    Dobler, Claudia C; Bosnic-Anticevich, Sinthia; Armour, Carol L

    2018-01-01

    The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds) and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk-benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters.

  1. Isoniazid Prophylaxis of Latent Tuberculous Infection among Healthcare Workers in Bamrasnaradura Infectious Diseases Institute

    Directory of Open Access Journals (Sweden)

    Patama Suttha

    2016-07-01

    Full Text Available Background: Treatment of latent tuberculosis infection (LTBI is one of the essential measures for tuberculosis (TB control. The tuberculin skin test (TST is an important tool for the detection of LTBI and the identification of healthcare workers (HCWs who require chemoprophylaxis. Also, the rate of active TB should be evaluated among HCWs with and without isoniazid (INH prophylactic treatment for LTBI. Objective: To evaluate the rate of active TB disease among HCWs with or without INH prophylaxis for LTBI. Methods: We retrospectively studied the clinical records of HCWs with LTBI at the employee TB screening clinic in Bamrasnaradura Infectious Diseases Institute from January 2008 to December 2010. Voluntary INH prophylaxis was recommended by physicians and nurses at the TB clinic in case of recent positive 2-step TST. The rate of active TB disease in HCWs with and without INH prophylaxis for LTBI was evaluated and followed during a period of 5 years. As well, the compliance and adverse effects of INH prophylaxis were identified by history taking. Results: There were 29 from 113 HCWS (25.7% receiving INH prophylaxis for 6 months (23 HCWs and 9 months (6 HCWs. 2 HCWs in each 6- and 9-month group did not complete INH prophylaxis for LTBI. After 5 years of TST, no case of active TB disease was found in HCWS with or without INH prophylaxis. Moreover, no adverse drug reactions were reported. Conclusion: No active tuberculosis disease was noted between the INH treatment and the control groups.

  2. Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection

    Directory of Open Access Journals (Sweden)

    Claudia C. Dobler

    2018-03-01

    Full Text Available The aim of the study was to explore the views of tuberculosis (TB physicians on treatment of latent TB infection (LTBI, focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk–benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters.

  3. Prevalence and associated risk factors of latent tuberculosis infection in a Spanish prison.

    Science.gov (United States)

    López de Goicoechea-Saiz, M E; Sternberg, F; Portilla-Sogorb, J

    2018-01-01

    To determine the prevalence of latent tuberculosis infection (LTI) in a Spanish prison, analyze the main sociodemographic and clinical variables associated with this condition and estimate the percentage of individuals with LTI who have received chemoprophylactic treatment. Cross-sectional study including inmates hosted in the Madrid VI Prison on 16/07/2016. Exclusion criteria: history of tuberculosis; non-updated tuberculin test according to the Tuberculosis Prevention and Control Program in Prisons protocol. Information of the variables was collected from SANIT and SIP programs, and by checking the clinical records of inmates. Description of the participant population and comparison between the frequency of distribution of the independent variables in LTI present and absent groups were performed, the last calculating the p value with Ji2 and Mann-Whitney U tests. Bivariate and multivariate analysis have been carried out with a logistic regression model. 936 individuals have been included. The prevalence of LTI in prison is 54.6%. This condition has been linked to the sociodemographic variables age, sex and nationality of origin, being age the one that has shown the strongest association. Among the other factors analyzed, only HCV infection behaves as a predictor of LTI. 30.3% of the individuals with LTI have completed or are receiving chemoprophylactic treatment in the moment of the study. LTI prevalence is high in the Spanish current prison population. The results of the study emphasize the relevance of the LTI screening in the prison setting, specially among high risk groups, and point out the need of a greater effort in the indication and completion of the chemoprophylactic treatment.

  4. Prevalence and associated risk factors of latent tuberculosis infection in a Spanish prison

    Directory of Open Access Journals (Sweden)

    ME López de Goicoechea-Saiz

    Full Text Available Abstract Aim: To determine the prevalence of latent tuberculosis infection (LTI in a Spanish prison, analyze the main sociodemographic and clinical variables associated with this condition and estimate the percentage of individuals with LTI who have received chemoprophylactic treatment. Materials and methods: Cross-sectional study including inmates hosted in the Madrid VI Prison on 16/07/2016. Exclusion criteria: history of tuberculosis; non-updated tuberculin test according to the Tuberculosis Prevention and Control Program in Prisons protocol. Information of the variables was collected from SANIT and SIP programs, and by checking the clinical records of inmates. Description of the participant population and comparison between the frequency of distribution of the independent variables in LTI present and absent groups were performed, the last calculating the p value with Ji2 and Mann-Whitney U tests. Bivariate and multivariate analysis have been carried out with a logistic regression model. Results: 936 individuals have been included. The prevalence of LTI in prison is 54.6%. This condition has been linked to the sociodemographic variables age, sex and nationality of origin, being age the one that has shown the strongest association. Among the other factors analyzed, only HCV infection behaves as a predictor of LTI. 30.3% of the individuals with LTI have completed or are receiving chemoprophylactic treatment in the moment of the study. Discussion: LTI prevalence is high in the Spanish current prison population. The results of the study emphasize the relevance of the LTI screening in the prison setting, specially among high risk groups, and point out the need of a greater effort in the indication and completion of the chemoprophylactic treatment.

  5. Prevalence of latent tuberculosis infection among health care workers in a hospital for pulmonary diseases

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    Diel Roland

    2009-01-01

    Full Text Available Abstract Background Little is known about the prevalence of latent tuberculosis infections (LTBI in health care workers (HCW in low-incidence countries especially in hospitals for pulmonary diseases. With Interferon-gamma release assays (IGRA, a new method for diagnosis of LTBI is available which is more specific than the tuberculin skin test (TST. Objectives The study was designed to estimate prevalence of LTBI among 270 HCW in a Hospital of Pulmonary Diseases routinely screened for TB. Methods LTBI was assessed by the QuantiFERON-Gold In Tube (QFT-IT. Information on gender, age, workplace, job title, BCG vaccination and history of both TB and TST were collected using a standardised questionnaire. Adjusted odds ratios for potential risk factors for LTBI were calculated. Results The prevalence of LTBI was 7.2%. In HCW younger than 30 years LTBI prevalence was 3.5% and in those older than 50 years 22%. Physicians and nurses showed a higher prevalence rate than other professions (10.8% to 4.5%. The putative risk factors for LTBI were age (>50 year OR 9.3, 95%CI 2.5–33.7, working as physicians/nurses (OR 3. 95%CI 1.2–10.4 and no previous TST in medical history (OR 4.4, 95%CI 1.01–18.9 when compared to those with a negative TST. Conclusion Prevalence of LTBI assessed by QFT-IT is low, this indicates a low infection risk even in hospitals for pulmonary diseases. No statement can be made regarding the occupational risk as compared to the general population because there are no LTBI prevalence data from Germany available. The higher LTBI prevalence rate in older HCWs might be due to the cohort effect or the longer time at risk.

  6. 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)

  7. Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital

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    Anand Bimari Janagond

    2017-01-01

    Full Text Available Background: Health-care workers (HCWs are at increased risk of acquiring tuberculosis (TB than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI burden in HCWs in the high burden countries is lacking. Methods: A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position, knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST using 5 international units (IU; 0.1 ml of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette–Guérin [BCG]. TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. Results: A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm the TST results suggested that 36.8% (76/206 were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography

  8. Expansion of murine gammaherpesvirus latently infected B cells requires T follicular help.

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    Christopher M Collins

    2014-05-01

    Full Text Available X linked lymphoproliferative disease (XLP is an inherited immunodeficiency resulting from mutations in the gene encoding the slam associated protein (SAP. One of the defining characteristics of XLP is extreme susceptibility to infection with Epstein-Barr virus (EBV, a gammaherpesvirus belonging to the genus Lymphocryptovirus, often resulting in fatal infectious mononucleosis (FIM. However, infection of SAP deficient mice with the related Murine gammaherpesvirus 68 (MHV68, a gammaherpesvirus in the genus Rhadinovirus, does not recapitulate XLP. Here we show that MHV68 inefficiently establishes latency in B cells in SAP deficient mice due to insufficient CD4 T cell help during the germinal center response. Although MHV68 infected B cells can be found in SAP-deficient mice, significantly fewer of these cells had a germinal center phenotype compared to SAP-sufficient mice. Furthermore, we show that infected germinal center B cells in SAP-deficient mice fail to proliferate. This failure to proliferate resulted in significantly lower viral loads, and likely accounts for the inability of MHV68 to induce a FIM-like syndrome. Finally, inhibiting differentiation of T follicular helper (TFH cells in SAP-sufficient C57Bl/6 mice resulted in decreased B cell latency, and the magnitude of the TFH response directly correlated with the level of infection in B cells. This requirement for CD4 T cell help during the germinal center reaction by MHV68 is in contrast with EBV, which is thought to be capable of bypassing this requirement by expressing viral proteins that mimic signals provided by TFH cells. In conclusion, the outcome of MHV68 infection in mice in the setting of loss of SAP function is distinct from that observed in SAP-deficient patients infected with EBV, and may identify a fundamental difference between the strategies employed by the rhadinoviruses and lymphocryptoviruses to expand B cell latency during the early phase of infection.

  9. The deterioration during transport and storage of tomato fruits by microorganisms contaminating the surface and latent infected tissue

    OpenAIRE

    河野, 又四; 寺下, 隆夫

    1988-01-01

    [Author abstract]Deterioration during transport and storage of tomato fruits is generally thought to be caused by microorganisms contaminating the surface and latent infected tissue of apparently healthy fruit. Counts of viable airborne microorganisms showed that there were more in plastic greenhouses than in open culure of tomatoes. Altemaria, Aspergillus niger, Asp. oryzae, Cladosporium, Fusarium, Mucor, Penicillium, Trichoderma, Trichothecium, Bacillus, Erwinia and Pseudomonas were among t...

  10. Investigation of Functional Activity of Cells in Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the New Ex Vivo Model

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    Elena Ufimtseva

    2013-01-01

    Full Text Available The new ex vivo model system measuring functional input of individual granuloma cells to formation of granulomatous inflammatory lesions in mice with latent tuberculous infection has been developed and described in the current study. Monolayer cultures of cells that migrated from individual granulomas were established in the proposed culture settings for mouse spleen and lung granulomas induced by in vivo exposure to BCG vaccine. The cellular composition of individual granulomas was analyzed. The expression of the leukocyte surface markers such as phagocytic receptors CD11b, CD11c, CD14, and CD16/CD32 and the expression of the costimulatory molecules CD80, CD83, and CD86 were tested as well as the production of proinflammatory cytokines (IFNγ and IL-1α and growth factors (GM-CSF and FGFb for cells of individual granulomas. The colocalization of the phagocytic receptors and costimulatory molecules in the surface microdomains of granuloma cells (with and without acid-fast BCG-mycobacteria has also been detected. It was found that some part of cytokine macrophage producers have carried acid-fast mycobacteria. Detected modulation in dynamics of production of pro-inflammatory cytokines, growth factors, and leukocyte surface markers by granuloma cells has indicated continued processes of activation and deactivation of granuloma inflammation cells during the latent tuberculous infection progress in mice.

  11. Investigation of Functional Activity of Cells in Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the New Ex Vivo Model

    Science.gov (United States)

    2013-01-01

    The new ex vivo model system measuring functional input of individual granuloma cells to formation of granulomatous inflammatory lesions in mice with latent tuberculous infection has been developed and described in the current study. Monolayer cultures of cells that migrated from individual granulomas were established in the proposed culture settings for mouse spleen and lung granulomas induced by in vivo exposure to BCG vaccine. The cellular composition of individual granulomas was analyzed. The expression of the leukocyte surface markers such as phagocytic receptors CD11b, CD11c, CD14, and CD16/CD32 and the expression of the costimulatory molecules CD80, CD83, and CD86 were tested as well as the production of proinflammatory cytokines (IFNγ and IL-1α) and growth factors (GM-CSF and FGFb) for cells of individual granulomas. The colocalization of the phagocytic receptors and costimulatory molecules in the surface microdomains of granuloma cells (with and without acid-fast BCG-mycobacteria) has also been detected. It was found that some part of cytokine macrophage producers have carried acid-fast mycobacteria. Detected modulation in dynamics of production of pro-inflammatory cytokines, growth factors, and leukocyte surface markers by granuloma cells has indicated continued processes of activation and deactivation of granuloma inflammation cells during the latent tuberculous infection progress in mice. PMID:24198843

  12. Sero-prevalence of latent Toxoplasma gondii infection among HIV-infected and HIV-uninfected people in Addis Ababa, Ethiopia: A comparative cross-sectional study

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    Tegbaru Belete

    2009-10-01

    Full Text Available Abstract Background Toxoplasmosis in immuno-compromised hosts manifests primarily as a life threatening condition, toxoplasmic encephalitis. However, there is scarce information about the magnitude of Toxoplasma gondii infection among HIV-infected people in Ethiopia. This study was, therefore, conducted to determine the sero-prevalence of T. gondii infection among HIV-infected and HIV-uninfected subjects. Findings Sera were collected from people with and without HIV infection for the purpose of studying hepatitis B virus (HBV at St. Paul Hospital, Addis Ababa, Ethiopia from 24 January 2007 to 15 February 2007. Among these sera, the first 330 consecutive sera, 165 from each HIV sero-group, were selected and tested for anti-T. gondii IgG antibodies using Enzyme Linked Immunosorbent Assay. The seroprevalence of Toxoplasma infection was assessed against socio-demographic characteristics, HIV and HBV serostatus and HBV-related risk factors. The overall sero-prevalence of latent T. gondii infection among the study subjects was 90.0%. Toxoplasma infection was observed with respective prevalence of 93.3% and 86.7% among HIV-infected and HIV-uninfected people. Though Toxoplasma infection seems to be influenced by age, gender and HIV serostatus, only HBV serostatus was significantly associated (OR 2.71, CI 1.12 to 6.57 in multivariate logistic regression analysis. Conclusion The seroprevalence of latent T. gondii infection is high and similar by HIV status. Educating people to prevent acquisition of new Toxoplasma infection and minimizing the risk of disease manifestations among HIV-Toxoplasma co-infected individuals is important.

  13. Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2.

    Science.gov (United States)

    Umbach, Jennifer L; Wang, Kening; Tang, Shuang; Krause, Philip R; Mont, Erik K; Cohen, Jeffrey I; Cullen, Bryan R

    2010-01-01

    Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (U(L)) region of the genome, 3' to the U(L)15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT.

  14. Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2▿

    Science.gov (United States)

    Umbach, Jennifer L.; Wang, Kening; Tang, Shuang; Krause, Philip R.; Mont, Erik K.; Cohen, Jeffrey I.; Cullen, Bryan R.

    2010-01-01

    Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (UL) region of the genome, 3′ to the UL15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT. PMID:19889786

  15. Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection.

    Science.gov (United States)

    Perry, Clarice L; Banasik, Brianne N; Gorder, Summer R; Xia, Jingya; Auclair, Sarah; Bourne, Nigel; Milligan, Gregg N

    2016-12-01

    Genital infections with herpes simplex virus type 2 (HSV-2) are a source of considerable morbidity and are a health concern for newborns exposed to virus during vaginal delivery. Additionally, HSV-2 infection diminishes the integrity of the vaginal epithelium resulting in increased susceptibility of individuals to infection with other sexually transmitted pathogens. Understanding immune protection against HSV-2 primary infection and immune modulation of virus shedding events following reactivation of the virus from latency is important for the development of effective prophylactic and therapeutic vaccines. Although the murine model of HSV-2 infection is useful for understanding immunity following immunization, it is limited by the lack of spontaneous reactivation of HSV-2 from latency. Genital infection of guinea pigs with HSV-2 accurately models the disease of humans including the spontaneous reactivation of HSV-2 from latency and provides a unique opportunity to examine virus-host interactions during latency. Although the guinea pig represents an accurate model of many human infections, relatively few reagents are available to study the immunological response to infection. To analyze the cell-mediated immune response of guinea pigs at extended periods of time after establishment of HSV-2 latency, we have modified flow-cytometry based proliferation assays and IFN-γ ELISPOT assays to detect and quantify HSV-specific cell-mediated responses during latent infection of guinea pigs. Here we demonstrate that a combination of proliferation and ELISPOT assays can be used to quantify and characterize effecter function of virus-specific immune memory responses during HSV-latency. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

    Science.gov (United States)

    Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

    2018-01-15

    Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

  17. Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling

    Science.gov (United States)

    Kloet, Serieke; Cobelens, Frank; Bootsma, Martin

    2018-01-01

    While tuberculosis (TB) represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation–either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995–2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting

  18. Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling.

    Directory of Open Access Journals (Sweden)

    Hester Korthals Altes

    Full Text Available While tuberculosis (TB represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI. Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation-either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers: Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-pulmonary TB cases from 1995-2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that

  19. Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling.

    Science.gov (United States)

    Korthals Altes, Hester; Kloet, Serieke; Cobelens, Frank; Bootsma, Martin

    2018-01-01

    While tuberculosis (TB) represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation-either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995-2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting

  20. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

    Science.gov (United States)

    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  1. Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis.

    Science.gov (United States)

    Zenner, Dominik; Beer, Netta; Harris, Ross J; Lipman, Marc C; Stagg, Helen R; van der Werf, Marieke J

    2017-08-15

    Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI. To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children. PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied. Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB). 2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol. The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy. Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies. Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin. U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).

  2. Prevalence of abnormal radiological findings in health care workers with latent tuberculosis infection and correlations with T cell immune response.

    Directory of Open Access Journals (Sweden)

    Rajnish Joshi

    2007-08-01

    Full Text Available More than half of all health care workers (HCWs in high TB-incidence, low and middle income countries are latently infected with tuberculosis (TB. We determined radiological lesions in a cohort of HCWs with latent TB infection (LTBI in India, and determined their association with demographic, occupational and T-cell immune response variables.We obtained chest radiographs of HCWs who had undergone tuberculin skin test (TST and QuantiFERON-TB Gold In Tube (QFT, an interferon-gamma release assay, in a previous cross-sectional study, and were diagnosed to have LTBI because they were positive by either TST or QFT, but had no evidence of clinical disease. Two observers independently interpreted these radiographs using a standardized data form and any discordance between them resolved by a third observer. The radiological diagnostic categories (normal, suggestive of inactive TB, and suggestive of active TB were compared with results of TST, QFT assay, demographic, and occupational covariates.A total of 330 HCWs with positive TST or QFT underwent standard chest radiography. Of these 330, 113 radiographs (34.2% were finally classified as normal, 206 (62.4% had lesions suggestive of inactive TB, and 11 (3.4% had features suggestive of active TB. The mean TST indurations and interferon-gamma levels in the HCWs in these three categories were not significantly different. None of the demographic or occupational covariates was associated with prevalence of inactive TB lesions on chest radiography.In a high TB incidence setting, nearly two-thirds of HCWs with latent TB infection had abnormal radiographic findings, and these findings had no clear correlation with T cell immune responses. Further studies are needed to verify these findings and to identify the causes and prognosis of radiologic abnormalities in health care workers.

  3. Mobile phone-based evaluation of latent tuberculosis infection: Proof of concept for an integrated image capture and analysis system.

    Science.gov (United States)

    Naraghi, Safa; Mutsvangwa, Tinashe; Goliath, René; Rangaka, Molebogeng X; Douglas, Tania S

    2018-05-08

    The tuberculin skin test is the most widely used method for detecting latent tuberculosis infection in adults and active tuberculosis in children. We present the development of a mobile-phone based screening tool for measuring the tuberculin skin test induration. The tool makes use of a mobile application developed on the Android platform to capture images of an induration, and photogrammetric reconstruction using Agisoft PhotoScan to reconstruct the induration in 3D, followed by 3D measurement of the induration with the aid of functions from the Python programming language. The system enables capture of images by the person being screened for latent tuberculosis infection. Measurement precision was tested using a 3D printed induration. Real-world use of the tool was simulated by application to a set of mock skin indurations, created by a make-up artist, and the performance of the tool was evaluated. The usability of the application was assessed with the aid of a questionnaire completed by participants. The tool was found to measure the 3D printed induration with greater precision than the current ruler and pen method, as indicated by the lower standard deviation produced (0.3 mm versus 1.1 mm in the literature). There was high correlation between manual and algorithm measurement of mock skin indurations. The height of the skin induration and the definition of its margins were found to influence the accuracy of 3D reconstruction and therefore the measurement error, under simulated real-world conditions. Based on assessment of the user experience in capturing images, a simplified user interface would benefit wide-spread implementation. The mobile application shows good agreement with direct measurement. It provides an alternative method for measuring tuberculin skin test indurations and may remove the need for an in-person follow-up visit after test administration, thus improving latent tuberculosis infection screening throughput. Copyright © 2018 Elsevier Ltd

  4. Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells

    Directory of Open Access Journals (Sweden)

    Shuo Liu

    2013-01-01

    Full Text Available By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.

  5. The p19 protein of Grapevine Algerian latent virus is a determinant of systemic infection of Chenopodium quinoa.

    Science.gov (United States)

    Kim, Semin; Cho, Won Kyong; Lee, Hyeok-Geun; Park, Sang-Ho; Sohn, Seong-Han; Kim, Kook-Hyung

    2012-04-01

    A previous study showed that both Grapevine Algerian latent virus (GALV) and Tomato bushy stunt virus (TBSV) systemically infect Nicotiana benthamiana, but GALV causes systemic infection whereas TBSV causes only local lesions in Chenopodium quinoa (C. quinoa). We recently isolated GALV strain Naju (GALV-N) from Limonium sinense and TBSV strain Sacheon (TBSV-S) from tomato. Both viruses belong to the genus Tombusvirus and have a similar genome organization. To identify determinants of systemic infection of GALV-N in C. quinoa in the current study, we generated infectious clones and capsid protein (CP)-deletion clones for the two viruses and confirmed that CP of GALV-N is required for systemic infection of C. quinoa due to its primary structural role in virus assembly. Through the use of chimeras, we identified a viral factor in addition to CP that contributes to systemic infection by GALV-N. Inactivation of the p19 demonstrated that host-specific activities of p19 are necessary for efficient systemic infection of C. quinoa by GALV-N. Our study is the first report to determine the viral factors required for systemic infection of GALV in C. quinoa. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis

    DEFF Research Database (Denmark)

    Diel, R; Goletti, D; Ferrara, G

    2011-01-01

    We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases...... of IGRAs varied 98-100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA...

  7. PR.Latent-class methods to evaluate diagnostics tests for echinococcus infections in dogs.

    NARCIS (Netherlands)

    Hartnack, S.; Budke, C.M.; Craig, P.S.; Jiamin, Q.; Boufana, B.; Campos Ponce, M.; Torgerson, P.R.

    2013-01-01

    Background: The diagnosis of canine echinococcosis can be a challenge in surveillance studies because there is no perfect gold standard that can be used routinely. However, unknown test specificities and sensitivities can be overcome using latent-class analysis with appropriate data. Methodology: We

  8. Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals

    Czech Academy of Sciences Publication Activity Database

    Trejbalová, K.; Kovářová, D.; Blažková, J.; Machala, L.; Jilich, D.; Weber, Jan; Kučerová, D.; Vencálek, O.; Hirsch, Ivan; Hejnar, J.

    2016-01-01

    Roč. 8, Feb 19 (2016), č. článku 19. ISSN 1868-7083 Institutional support: RVO:61388963 Keywords : HIV-1 * latent reservoir * DNA methylation * chromatin conformation * latent HIV-1 provirus reactivation * HIV-1-infected individuals Subject RIV: EE - Microbiology, Virology Impact factor: 4.987, year: 2016 http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0185-6

  9. Development of 5 ' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals

    Czech Academy of Sciences Publication Activity Database

    Trejbalová, Kateřina; Kovářová, Denisa; Blažková, Jana; Machala, L.; Jilich, D.; Weber, J.; Kučerová, Dana; Vencálek, O.; Hirsch, Ivan; Hejnar, Jiří

    2016-01-01

    Roč. 8, zima (2016), č. článku 19. ISSN 1868-7083 R&D Projects: GA ČR GAP304/12/1736 Institutional support: RVO:68378050 Keywords : HIV-1 * latent reservoir * DNA methylation * chromatin conformation * latent HIV-1 provirus reactivation * HIV-1-infected individuals Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.987, year: 2016

  10. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection

    Science.gov (United States)

    Belknap, Robert; Holland, David; Feng, Pei-Jean; Millet, Joan-Pau; Caylà, Joan A.; Martinson, Neil A.; Wright, Alicia; Chen, Michael P.; Moro, Ruth N.; Scott, Nigel A.; Arevalo, Bert; Miró, José M.; Villarino, Margarita E.; Weiner, Marc; Borisov, Andrey S.

    2017-01-01

    Background Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event–monitoring devices for self-administration. The main secondary outcome was adverse events. Results Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration–with–reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met

  11. Influence of diabetes mellitus and risk factors in activating latent tuberculosis infection: a case for targeted screening in malaysia.

    Science.gov (United States)

    Swarna Nantha, Y

    2012-10-01

    A review of the epidemiology of tuberculosis, its contributing risk factors (excluding HIV) and the role of screening latent tuberculosis infection in Malaysia was done. Despite the global and domestic decrease in prevalence rates of tuberculosis in the past decade, there is an alarming increase in the trend of non communicable diseases in the country. High prevalence rates of major risk factors leading to reactivation of tuberculosis were seen within the population, with diabetes mellitus being in the forefront. The rising numbers in the ageing population of Malaysia poses a further threat of re-emergence of tuberculosis in the years to come. Economically, screening of diabetic patients with comorbidities for latent tuberculosis infection (LTBI) using two major techniques, namely tuberculin sensitivity (TST) and Interferon gamma release assay tests (IGRA) could be a viable option. The role of future research in the detection of LTBI in the Malaysian setting might be necessary to gauge the disease reservoir before implementing prophylactic measures for high risk groups involved.

  12. THE CELLS WITH MYCOBACTERIA IN GRANULOMATOUS AGGREGATES FROM MICE WITH LATENT TUBERCULOUS INFECTION IN EX VIVO CULTURE

    Directory of Open Access Journals (Sweden)

    E. G. Ufimtseva

    2013-01-01

    Full Text Available Abstract. The aim of this study was to obtain ex vivo monolayer culture cells migrated from individual granulomas isolated from the spleens of the Balb/c line mice through 1–2 months after BCG vaccine infection. The second goal was to evaluate influence of different types of cells in the development of granulomatic inflammation and analysis of BCG bacteria content in these cells in the latent stage of tuberculosis. Granulomas were presented by macrophages in general. The number of granulomas was varied as in one mouse as between mice. Granulomas contained also dendritic cells (in average 10% from macrophages of granulomas and lymphocytes. In some granulomas fibroblasts, neutrophils, eosiniphils, multinuclear cells of Pirogov–Langhans, megacariocytes and platelets were observed in all stages of infection. The number of these cells was also varied between granulomas. The acid staining BCG bacteria were only detected in macrophages, dendritic cells and Pirogov–Langhans cells of mice granulomas. Mice were different as by number of cells with BCG bacteria in granulomas as by number of granulomas with BCG-containing cells. The proposed model of granuloma cells of mice in ex vivo culture can be used to study interaction between host cells and mycobacteria to find new ways and methods of influence to intracellular pathogens in latent stage of tuberculosis. 

  13. Prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Pedro Torres-Gonzalez

    Full Text Available BACKGROUND: Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW exposed in settings with poor control of bovine tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin skin test (TST and Interferon-gamma release assay (IGRA were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI was 76.2% (95% CI, 71.4-80.9% by TST and 58.5% (95% CI, 53.0-64.0% by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31-5.64 and IGRA (OR 2.38; 95% CI, 1.31-4.30 adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines. CONCLUSIONS: We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.

  14. Established and potential risk factors for clostridum difficile infection

    Directory of Open Access Journals (Sweden)

    Vaishnavi C

    2009-01-01

    Full Text Available Clostridium difficile is the aetiological agent for almost all cases of pseudo membranous colitis and 15-25% of antibiotic associated diarrhoea. In recent years, C. difficile associated disease (CDAD has been increasing in frequency and severity due to the emergence of virulent strains. Severe cases of toxic mega colon may be associated with mortality rates of 24-38%. The prevalence of CDAD is global and the incidence varies considerably from place to place. In the initial stages of its discovery, C. difficile infection was regarded mainly as an outcome of antibiotic intake and not as a life threatening disease. Intervention by man has produced conditions making C. difficile a significant cause of morbidity and mortality. The recent outbreak of CDAD in Quebec has sent the alarm bells ringing. Apart from a threefold increase in the incidence of CDAD, clinicians have also reported a higher number of cases involving toxic mega colon, colectomy or death. Among all the risk factors, inclusive of the host and the environmental factors, antibiotics are the most important ones. Surgical patients comprise 55-75% of all patients with CDAD due to the fact that perioperative prophylaxis requires the use of antibiotics. However, other drugs such as immunosuppressants and proton pump inhibitors are also important risk factors. Thus CDAD is a growing nosocomial and public health challenge. Additionally, the recognition of community acquired CDAD signals the presence of several risk factors. In this review, the established and potential risk factors of CDAD, along with the epidemiology, diagnostic modalities, management and preventive measures of the disease have been elaborated.

  15. Construction of a System for the Strawberry Nursery Production towards Elimination of Latent Infection of Anthracnose Fungi by a Combination of PCR and Microtube Hybridization

    Science.gov (United States)

    Furuta, Kazuyoshi; Nagashima, Saki; Inukai, Tsuyoshi; Masuta, Chikara

    2017-01-01

    One of the major problems in strawberry production is difficulty in diagnosis of anthracnose caused by Colletotrichum acutatum or Glomerella cingulata in latent infection stage. We here developed a diagnostic tool for the latent infection consisting of initial culturing of fungi, DNA extraction, synthesis of PCR-amplified probes and microtube hybridization (MTH) using a macroarray. The initial culturing step is convenient to lure the fungi out of the plant tissues, and to extract PCR-inhibitor-free DNA directly from fungal hyphae. For specific detection of the fungi, PCR primers were designed to amplify the fungal MAT1-2 gene. The subsequent MTH step using the PCR products as probes can replace the laborious electrophoresis step providing us sequence information and high-throughput screening. Using this method, we have conducted a survey for a few thousands nursery plants every year for three consecutive years, and finally succeeded in eliminating latent infection in the third year of challenge. PMID:28167891

  16. Construction of a System for the Strawberry Nursery Production towards Elimination of Latent Infection of Anthracnose Fungi by a Combination of PCR and Microtube Hybridization

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Furuta

    2017-02-01

    Full Text Available One of the major problems in strawberry production is difficulty in diagnosis of anthracnose caused by Colletotrichum acutatum or Glomerella cingulata in latent infection stage. We here developed a diagnostic tool for the latent infection consisting of initial culturing of fungi, DNA extraction, synthesis of PCR-amplified probes and microtube hybridization (MTH using a macroarray. The initial culturing step is convenient to lure the fungi out of the plant tissues, and to extract PCR-inhibitor-free DNA directly from fungal hyphae. For specific detection of the fungi, PCR primers were designed to amplify the fungal MAT1-2 gene. The subsequent MTH step using the PCR products as probes can replace the laborious electrophoresis step providing us sequence information and high-throughput screening. Using this method, we have conducted a survey for a few thousands nursery plants every year for three consecutive years, and finally succeeded in eliminating latent infection in the third year of challenge.

  17. Construction of a System for the Strawberry Nursery Production towards Elimination of Latent Infection of Anthracnose Fungi by a Combination of PCR and Microtube Hybridization.

    Science.gov (United States)

    Furuta, Kazuyoshi; Nagashima, Saki; Inukai, Tsuyoshi; Masuta, Chikara

    2017-02-01

    One of the major problems in strawberry production is difficulty in diagnosis of anthracnose caused by Colletotrichum acutatum or Glomerella cingulata in latent infection stage. We here developed a diagnostic tool for the latent infection consisting of initial culturing of fungi, DNA extraction, synthesis of PCR-amplified probes and microtube hybridization (MTH) using a macroarray. The initial culturing step is convenient to lure the fungi out of the plant tissues, and to extract PCR-inhibitor-free DNA directly from fungal hyphae. For specific detection of the fungi, PCR primers were designed to amplify the fungal MAT1-2 gene. The subsequent MTH step using the PCR products as probes can replace the laborious electrophoresis step providing us sequence information and high-throughput screening. Using this method, we have conducted a survey for a few thousands nursery plants every year for three consecutive years, and finally succeeded in eliminating latent infection in the third year of challenge.

  18. Interferon gamma release assays for the diagnosis of latent TB infection in HIV-infected individuals in a low TB burden country.

    LENUS (Irish Health Repository)

    Cheallaigh, Clíona Ní

    2013-01-01

    Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting.

  19. Hit-and-run stimulation: a novel concept to reactivate latent HIV-1 infection without cytokine gene induction.

    Science.gov (United States)

    Wolschendorf, Frank; Duverger, Alexandra; Jones, Jennifer; Wagner, Frederic H; Huff, Jason; Benjamin, William H; Saag, Michael S; Niederweis, Michael; Kutsch, Olaf

    2010-09-01

    Current antiretroviral therapy (ART) efficiently controls HIV-1 replication but fails to eradicate the virus. Even after years of successful ART, HIV-1 can conceal itself in a latent state in long-lived CD4(+) memory T cells. From this latent reservoir, HIV-1 rebounds during treatment interruptions. Attempts to therapeutically eradicate this viral reservoir have yielded disappointing results. A major problem with previously utilized activating agents is that at the concentrations required for efficient HIV-1 reactivation, these stimuli trigger high-level cytokine gene expression (hypercytokinemia). Therapeutically relevant HIV-1-reactivating agents will have to trigger HIV-1 reactivation without the induction of cytokine expression. We present here a proof-of-principle study showing that this is a possibility. In a high-throughput screening effort, we identified an HIV-1-reactivating protein factor (HRF) secreted by the nonpathogenic bacterium Massilia timonae. In primary T cells and T-cell lines, HRF triggered a high but nonsustained peak of nuclear factor kappa B (NF-kappaB) activity. While this short NF-kappaB peak potently reactivated latent HIV-1 infection, it failed to induce gene expression of several proinflammatory NF-kappaB-dependent cellular genes, such as those for tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and gamma interferon (IFN-gamma). Dissociation of cellular and viral gene induction was achievable, as minimum amounts of Tat protein, synthesized following application of a short NF-kappaB pulse, triggered HIV-1 transactivation and subsequent self-perpetuated HIV-1 expression. In the absence of such a positive feedback mechanism, cellular gene expression was not sustained, suggesting that strategies modulating the NF-kappaB activity profile could be used to selectively trigger HIV-1 reactivation.

  20. Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

    Science.gov (United States)

    Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

    2018-02-21

    The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

  1. HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

    Science.gov (United States)

    Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

    2017-09-15

    Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal Ganglia.

    Science.gov (United States)

    Sawtell, Nancy M; Thompson, Richard L

    2016-09-01

    The life long relationship between herpes simplex virus and its host hinges on the ability of the virus to aggressively replicate in epithelial cells at the site of infection and transport into the nervous system through axons innervating the infection site. Interaction between the virus and the sensory neuron represents a pivot point where largely unknown mechanisms lead to a latent or a lytic infection in the neuron. Regulation at this pivot point is critical for balancing two objectives, efficient widespread seeding of the nervous system and host survival. By combining genetic and in vivo in approaches, our studies reveal that the balance between latent and lytic programs is a process occurring early in the trigeminal ganglion. Unexpectedly, activation of the latent program precedes entry into the lytic program by 12 -14hrs. Importantly, at the individual neuronal level, the lytic program begins as a transition out of this acute stage latent program and this escape from the default latent program is regulated by de novo VP16 expression. Our findings support a model in which regulated de novo VP16 expression in the neuron mediates entry into the lytic cycle during the earliest stages of virus infection in vivo. These findings support the hypothesis that the loose association of VP16 with the viral tegument combined with sensory axon length and transport mechanisms serve to limit arrival of virion associated VP16 into neuronal nuclei favoring latency. Further, our findings point to specialized features of the VP16 promoter that control the de novo expression of VP16 in neurons and this regulation is a key component in setting the balance between lytic and latent infections in the nervous system.

  3. Cis and trans acting factors involved in human cytomegalovirus experimental and natural latent infection of CD14 (+ monocytes and CD34 (+ cells.

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    Cyprian C Rossetto

    Full Text Available The parameters involved in human cytomegalovirus (HCMV latent infection in CD14 (+ and CD34 (+ cells remain poorly identified. Using next generation sequencing we deduced the transcriptome of HCMV latently infected CD14 (+ and CD34 (+ cells in experimental as well as natural latency settings. The gene expression profile from natural infection in HCMV seropositive donors closely matched experimental latency models, and included two long non-coding RNAs (lncRNAs, RNA4.9 and RNA2.7 as well as the mRNAs encoding replication factors UL84 and UL44. Chromatin immunoprecipitation assays on experimentally infected CD14 (+ monocytes followed by next generation sequencing (ChIP-Seq were employed to demonstrate both UL84 and UL44 proteins interacted with the latent viral genome and overlapped at 5 of the 8 loci identified. RNA4.9 interacts with components of the polycomb repression complex (PRC as well as with the MIE promoter region where the enrichment of the repressive H3K27me3 mark suggests that this lncRNA represses transcription. Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE, which identifies nucleosome-depleted viral DNA, was used to confirm that latent mRNAs were associated with actively transcribed, FAIRE analysis also showed that the terminal repeat (TR region of the latent viral genome is depleted of nucleosomes suggesting that this region may contain an element mediating viral genome maintenance. ChIP assays show that the viral TR region interacts with factors associated with the pre replication complex and a plasmid subclone containing the HCMV TR element persisted in latently infected CD14 (+ monocytes, strongly suggesting that the TR region mediates viral chromosome maintenance.

  4. IGRA-Based Screening for Latent Tuberculosis Infection in Persons Newly Incarcerated in New York City Jails.

    Science.gov (United States)

    Katyal, Monica; Leibowitz, Ruth; Venters, Homer

    2018-04-01

    In the United States, latent tuberculosis infection (LTBI) detection in correctional settings is a public health priority. Interferon gamma release assay (IGRA)-based LTBI screening was introduced in New York City jails in 2011 to 2012, replacing historically used tuberculin skin testing (TST), which was associated with substantial incomplete screening rates. This retrospective, cross-sectional study evaluated LTBI screening outcomes and correlates of positivity in 40,986 persons newly incarcerated in 2011 to 2013. Of 35,090 eligible patients tested (96.4%), final results were 6.3% positive, 93.4% negative, and 0.2% indeterminate. In multivariable regression modeling, sex, age, race/ethnicity, nativity, marital status, prior jail incarceration, and HIV status were correlated with positivity. IGRA-based screening yielded high screening and low indeterminate test rates and may be recommended in correctional and other settings where TST is currently used.

  5. Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study.

    Science.gov (United States)

    Ncayiyana, Jabulani R; Bassett, Jean; West, Nora; Westreich, Daniel; Musenge, Eustasius; Emch, Michael; Pettifor, Audrey; Hanrahan, Colleen F; Schwartz, Sheree R; Sanne, Ian; van Rie, Annelies

    2016-11-08

    South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI RESULTS: The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0-14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01-1.05), male gender (OR = 2.70, 95 % CI = 1.55-4.70), marital status (OR = 2.00, 95 % CI = 1.31-3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04-4.31). The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty.

  6. Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

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    Elena Ufimtseva

    2016-01-01

    Full Text Available The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells.

  7. Strategy to better select HIV-infected individuals for latent TB treatment in BCG-vaccinated population.

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    Chin-Hui Yang

    Full Text Available OBJECTIVE: To evaluate the T-SPOT.TB interferon-γ releasing assay and the tuberculin skin test (TST, for the diagnosis of latent tuberculosis infection(LTBI and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals. METHODS: HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB. RESULTS: Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results, and the incidence was 0.17 per 100 person-years. The relative risks (RRs for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1-767.9, 73.9 (95% CI 3.9-1397.7 and 226.5 (95% CI 12.0-4284, respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively. CONCLUSIONS: Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.

  8. ß-catenin, a transcription factor activated by canonical Wnt signaling, is expressed in sensory neurons of calves latently infected with bovine herpesvirus 1

    Science.gov (United States)

    Like many a-herpesvirinae subfamily members, bovine herpes virus 1 (BoHV-1) expresses an abundant transcript in latently infected sensory neurons: the latency-related (LR) RNA. LR-RNA encodes a protein (ORF2) that inhibits apoptosis, interacts with Notch family members, interferes with Notch mediate...

  9. Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection

    Science.gov (United States)

    Lin, Jingwen; Cunningham, Deirdre; Tumwine, Irene; Kushinga, Garikai; McLaughlin, Sarah; Spence, Philip; Böhme, Ulrike; Sanders, Mandy; Conteh, Solomon; Bushell, Ellen; Metcalf, Tom; Billker, Oliver; Duffy, Patrick E.; Newbold, Chris; Berriman, Matthew; Langhorne, Jean

    2017-01-01

    Malaria is caused by parasites of the genus Plasmodium. All human-infecting Plasmodium species can establish long-lasting chronic infections1–5, creating an infectious reservoir to sustain transmission1,6. It is widely accepted that maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation7. However, genes involved in this process have been identified in only two of five human-infecting species: P. falciparum and P. knowlesi. Furthermore, little is understood about the early events in establishment of chronic infection in these species. Using a rodent model we demonstrate that only a minority of parasites from among the infecting population, expressing one of several clusters of virulence-associated pir genes, establishes a chronic infection. This process occurs in different species of parasite and in different hosts. Establishment of chronicity is independent of adaptive immunity and therefore different from the mechanism proposed for maintainance of chronic P. falciparum infections7–9. Furthermore, we show that the proportions of parasites expressing different types of pir genes regulate the time taken to establish a chronic infection. Since pir genes are common to most, if not all, species of Plasmodium10, this process may be a common way of regulating the establishment of chronic infections. PMID:28165471

  10. Latent tuberculosis infection in individuals with human immunodeficiency virus infection: comparison of tuberculin skin test to the anti TB-IgM antibodies

    International Nuclear Information System (INIS)

    Alvi, S.M.; Nadimi, M.; Shokri, S.; Zamani, G.A.

    2010-01-01

    To determine Latent Tuberculosis Infection (LTBI) prevalence and compare TST results to the anti TB-IgM anti bodies (ATIA) for the diagnosis of LTBI in HIV infected individuals. Sixty two randomized sampled HIV infected subjects from an addict treatment center in Ahvaz southwest Iran underwent TST, using 5 TU of purified protein derivative, and measuring ATIA. Data were analyzed in SPSS (version 16, USA). Of 62 participants, 34 (54.8%) had positive result for TST, whereas 6(9.7%) had positive ATIA. Overall concordance between TST and ATIA was 45.2% (Kappa= 0.37, P = 0.32). In subjects with positive test results by either TST or ATIA, only 4.8% had positive test results by both tests. Discordant results were found in 54.8% of subjects. Positive results for both tests in subjects categorized in two groups (above and below 200 CD4-cell/mm3) had no significant difference (P>0.05). LTBI prevalence among HIV infected individuals in studied area is higher than other parts of the world. TST is a useful test for LTBI diagnosis and prefer to ATIA. Concordance between TST and ATIA is low. (author)

  11. Effect of Pregnancy on Interferon Gamma Release Assay and Tuberculin Skin Test Detection of Latent TB Infection Among HIV-Infected Women in a High Burden Setting.

    Science.gov (United States)

    LaCourse, Sylvia M; Cranmer, Lisa M; Matemo, Daniel; Kinuthia, John; Richardson, Barbra A; Horne, David J; John-Stewart, Grace

    2017-05-01

    Peripartum immunologic changes may affect latent tuberculosis infection (LTBI) diagnostic performance among HIV-infected women. HIV-infected women were serially tested with tuberculin skin test (TST) and interferon gamma release assay [QuantiFERON TB Gold In-tube (QFT)] in pregnancy and 6 weeks postpartum in Kenya. Prevalence, sensitivity and agreement, and correlates of QFT/TST positivity were assessed. Quantitative QFT mitogen and Mycobacterium tuberculosis antigen (Mtb-Ag) responses were compared by peripartum stage. Incidence of test conversion at 6 weeks postpartum was evaluated in baseline TST-/QFT- women. Among 100 HIV-infected women, median age was 26 years, median CD4 was 555 cells per cubic millimeter, and 88% were on antiretrovirals. More women were QFT+ than TST+ in both pregnancy (35.4% vs. 13.5%, P = 0.001) and postpartum (29.6% vs. 14.8%, P pregnancy vs. postpartum, and specifically among persistently QFT+ women (Mtb-Ag: 3.46 vs. 4.48 IU/mL, P = 0.007). QFT indeterminate rate was higher in pregnancy (16%) compared with postpartum (0%) because of lower mitogen response. QFT identified >2-fold more women with LTBI compared with TST in pregnancy and postpartum. Lower QFT Mtb-Ag and mitogen responses in pregnancy compared with postpartum suggest that pregnancy-associated immunologic changes may influence LTBI test performance.

  12. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

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    Lawrence Shih-Hsin Wu

    2014-01-01

    Full Text Available Tuberculosis (TB is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI, with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  13. Systematic expression profiling analysis identifies specific microRNA-gene interactions that may differentiate between active and latent tuberculosis infection.

    Science.gov (United States)

    Wu, Lawrence Shih-Hsin; Lee, Shih-Wei; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che; Weng, Julia Tzu-Ya

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic--the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  14. 'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology.

    Science.gov (United States)

    Honigsbaum, Mark

    2016-04-01

    The Swiss-born medical researcher Karl Friedrich Meyer (1884-1974) is best known as a 'microbe hunter' who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer's 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a 'reservoir of disease' as a forerunner of 'one medicine' approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer's other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer-like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet-can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet's and Smith's contributions to this scientific field have been widely acknowledged, Meyer's have been largely ignored. Drawing on Meyer's published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer's intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague-exchanges that not only showed how environmental and ecological conditions could 'tip the balance' in favor of parasites but which transformed Meyer thinking about resistance to infection and disease.

  15. Prevalence and correlates of latent tuberculosis infection among employees of a high security prison in Malaysia.

    Science.gov (United States)

    Al-Darraji, Haider Abdulrazzaq Abed; Tan, Cynthia; Kamarulzaman, Adeeba; Altice, Frederick L

    2015-06-01

    Although prison employees share the same tuberculosis (TB) risk environment with prisoners, the magnitude of TB problems among prison employees is unknown in most resource-limited prisons. This survey was conducted to investigate the prevalence and correlates of tuberculin skin test (TST) positivity among employees in Malaysia's largest prison. Consented, full-time prison employees were interviewed using a structured questionnaire that included sociodemographic data, history of working in the correctional system and TB-related risk. TST was placed intradermally and read after 48-72 h. Induration size of ≥10 mm was considered positive. Logistic regression analyses were conducted to explore associations with TST positivity. Of the 445 recruited prison employees, 420 (94.4%) had complete data. Most were young (median=30.0 years) men (88.8%) who had only worked at this prison (76.4%) for a median total employment period of 60 months (IQR 34.5-132.0). The majority were correctional officers, while civilian employees represented only 7.6% of the sample. Only 26 (6.2%) reported having ever been screened for TB since employment. Prevalence of TST positivity was 81% and was independently associated with longer (≥12 months) prison employment (AOR 4.9; 95% CI 1.5 to 15.9) and current tobacco smoking (AOR=1.9, 95% CI 1.2 to 3.2). Latent TB prevalence was high in this sample, approximating that of prisoners in this setting, perhaps suggesting within prison TB transmission in this facility. Formal TB control programmes for personnel and prisoners alike are urgently needed within the Malaysian correctional system. 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.

  16. Latent infection with Leishmania donovani in highly endemic villages in Bihar, India.

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    Epco Hasker

    Full Text Available Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We describe patterns of markers of Leishmania donovani infection and clinical VL in relation to age in Bihar, India.We selected eleven villages highly endemic for Leishmania donovani. During a 1-year interval we conducted two house to house surveys during which we collected blood samples on filter paper from all consenting individuals aged 2 years and above. Samples were tested for anti-leishmania serology by Direct Agglutination Test (DAT and rK39 ELISA. Data collected during the surveys included information on episodes of clinical VL among study participants.We enrolled 13,163 persons; 6.2% were reactive to DAT and 5.9% to rK39. Agreement between the tests was weak (kappa = 0.30. Among those who were negative on both tests at baseline, 3.6% had converted to sero-positive on either of the two tests one year later. Proportions of sero-positives and sero-converters increased steadily with age. Clinical VL occurred mainly among children and young adults (median age 19 years.Although infection with L. donovani is assumed to be permanent, serological markers revert to negative. Most VL cases occur at younger ages, yet we observed a steady increase with age in the frequency of sero-positivity and sero-conversion. Our findings can be explained by a boosting effect upon repeated exposure to the parasite or by intermittent release of parasites in infected subjects from safe target cells. A certain proportion of sero-negative subjects could have been infected but below the threshold of antibody abundance for our serologic testing.

  17. Cytokine profile in patients with early latent syphilis

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    Zakharov S.V.

    2018-03-01

    Full Text Available The purpose of this study was to study the change in the content of the most active cytokines (interleukins 6 and 10 during the formation of the immune response in patients with latent early syphilis, as well as to study the possible relationship between the concentrations of these cytokines and the duration of the disease. In 50 patients with early latent syphilis, the concentration of interleukins 6 and 10 in serum was studied. The serum level of interleukins was studied by the enzyme immunoassay. A statistically significant increase in the concentration of interleukin 6 in the blood of patients with latent syphilis and decrease in the interleukin 10 concentration in comparison with healthy people was established. At the same time, in patients with latent syphilis with term of infection for more than 1 year, interleukin 10 has been expressed, as compared with healthy people and, especially, with patients with syphilis with a duration of infection of up to 1 year. Along with this, a lower degree of increase in the concentration of interleukin 6 in patients with latent syphilis with a duration of infection over 1 year has been established, as compared with patients with latent syphilis with a term of infection up to 1 year, against the background of its increased concentration as compared with a group of healthy individuals.

  18. No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

    Science.gov (United States)

    Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

    2010-01-01

    Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

  19. Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Madrid-Elena, Nadia; García-Bermejo, María Laura; Serrano-Villar, Sergio; Díaz-de Santiago, Alberto; Sastre, Beatriz; Gutiérrez, Carolina; Dronda, Fernando; Coronel Díaz, María; Domínguez, Ester; López-Huertas, María Rosa; Hernández-Novoa, Beatriz; Moreno, Santiago

    2018-02-14

    Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency reversing potential of maraviroc and the mechanisms involved, we performed a phase-II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (Eudra CT: 2012-003215-66). All patients completed full maraviroc dosing and follow up. The primary endpoint was to study whether maraviroc may reactivate HIV-1 latency, eliciting signalling pathways involved in the viral reactivation. An increase in HIV-1 transcription in resting CD4 + T-cells, estimated by HIV-1 unspliced RNA, was observed. Moreover, activation of the NF-κB transcription factor was observed in these cells. In contrast, AP-1 and NFAT activity was not detected. To elucidate the mechanism of NF-κB activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably express CCR5, if maraviroc could be acting as a partial CCR5-agonist, with no other mechanisms or pathways involved. Our results show that maraviroc can induce NF-κB activity and NF-κB target genes expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-κB activation and functionality. Taken together, we show that maraviroc may have a role in the activation of latent virus transcription through the activation of NF-κB as a result of binding CCR5. Our results strongly support a novel use of maraviroc as a potential latency reversal agent in HIV-1-infected patients. IMPORTANCE HIV-1 persistence in a small pool of long-lived latently infected resting CD4 + T-cells is a major barrier to viral eradication in HIV-1-infected patients on antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use of latency reversing agents to eliminate the reservoirs established in resting CD4 + T-cells. As no drug has been shown to be completely

  20. Infection cycle of Artichoke Italian latent virus in tobacco plants: meristem invasion and recovery from disease symptoms.

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    Elisa Santovito

    Full Text Available Nepoviral infections induce recovery in fully expanded leaves but persist in shoot apical meristem (SAM by a largely unknown mechanism. The dynamics of infection of a grapevine isolate of Artichoke Italian latent virus (AILV-V, genus Nepovirus in tobacco plants, including colonization of SAM, symptom induction and subsequent recovery of mature leaves from symptoms, were characterized. AILV-V moved from the inoculated leaves systemically and invaded SAM in 7 days post-inoculation (dpi, remaining detectable in SAM at least up to 40 dpi. The new top leaves recovered from viral symptoms earliest at 21 dpi. Accumulation of viral RNA to a threshold level was required to trigger the overexpression of RDR6 and DCL4. Consequently, accumulation of viral RNA decreased in the systemically infected leaves, reaching the lowest concentration in the 3rd and 4th leaves at 23 dpi, which was concomitant with recovery of the younger, upper leaves from disease symptoms. No evidence of virus replication was found in the recovered leaves, but they contained infectious virus particles and were protected against re-inoculation with AILV-V. In this study we also showed that AILV-V did not suppress initiation or maintenance of RNA silencing in transgenic plants, but was able to interfere with the cell-to-cell movement of the RNA silencing signal. Our results suggest that AILV-V entrance in SAM and activation of RNA silencing may be distinct processes since the latter is triggered in fully expanded leaves by the accumulation of viral RNA above a threshold level rather than by virus entrance in SAM.

  1. Senescence as a Factor in Latent Pathogen Infection in Eurasian Watermilfoil

    Science.gov (United States)

    2009-09-01

    organisms that colonize plant tissues at some time in their life without causing harm to their host (Petrini 1991). They include micro - organisms...declines including nutrient depletion, shading by phytoplankton and algae , attack by parasites and pathogens, long-term effects of harvesting and/or...Center (ERDC), Environmental Laboratory, Vicksburg, MS. Endophyte-infected plants were collected from a culture pond at the Lewisville Aquatic

  2. Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.

    Science.gov (United States)

    Weiner, Marc; Savic, Radojka M; Kenzie, William R Mac; Wing, Diane; Peloquin, Charles A; Engle, Melissa; Bliven, Erin; Prihoda, Thomas J; Gelfond, Jonathan A L; Scott, Nigel A; Abdel-Rahman, Susan M; Kearns, Gregory L; Burman, William J; Sterling, Timothy R; Villarino, M Elsa

    2014-06-01

    In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults. Published by Oxford University Press on behalf of the Pediatric Infectious

  3. Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens.

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    Cynthia J Snider

    Full Text Available Plasmodium falciparum malaria (Pf-malaria and Epstein Barr Virus (EBV infections coexist in children at risk for endemic Burkitt's lymphoma (eBL; yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years in Kenya from 2002-2004. Prevalence ratios (PR and 95% confidence intervals (CI were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5-9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30-0.99. Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5-9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.

  4. Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

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    Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

    2016-03-01

    A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

  5. Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico.

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    Oren, Eyal; Alatorre-Izaguirre, Gabriela; Vargas-Villarreal, Javier; Moreno-Treviño, Maria Guadalupe; Garcialuna-Martinez, Javier; Gonzalez-Salazar, Francisco

    2015-01-01

    Nearly one-third of the world's population is infected with latent tuberculosis (LTBI). Tuberculosis (TB) rates in the border states are higher than national rates in both the US and Mexico, with the border accounting for 30% of total registered TB cases in both countries. However, LTBI rates in the general population in Mexican border states are unknown. In this region, LTBI is diagnosed using the tuberculin skin test (TST). New methods of detection more specific than TST have been developed, although there is currently no gold standard for LTBI detection. Our objective is to demonstrate utility of the Quantiferon TB gold In-Tube (QFT-GIT) test compared with the TST to detect LTBI among border populations. This is an observational, cross-sectional study carried out in border areas of the states of Nuevo Leon and Tamaulipas, Mexico. Participants (n = 210) provided a TST and blood sample for the QFT-GIT. Kappa coefficients assessed the agreement between TST and QFT-GIT. Participant characteristics were compared using Fisher exact tests. Thirty-eight percent of participants were diagnosed with LTBI by QFT-GIT. The proportion of LTBI detected using QFT-GIT was almost double [38% (79/210)] that found by TST [19% (39/210)] (P < 0.001). Concordance between TST and QFT-GIT was low (kappa = 0.37). We recommend further studies utilizing the QFT-GIT test to detect LTBI among border populations.

  6. Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States

    Science.gov (United States)

    Shepardson, D.; Marks, S. M.; Chesson, H.; Kerrigan, A.; Holland, D. P.; Scott, N.; Tian, X.; Borisov, A. S.; Shang, N.; Heilig, C. M.; Sterling, T. R.; Villarino, M. E.; Mac Kenzie, W. R.

    2017-01-01

    SUMMARY SETTING A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES To assess the cost-effectiveness of 3HP compared to 9H. DESIGN A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21 525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease. PMID:24200264

  7. Predictors of latent tuberculosis infection treatment completion in the US private sector: an analysis of administrative claims data.

    Science.gov (United States)

    Stockbridge, Erica L; Miller, Thaddeus L; Carlson, Erin K; Ho, Christine

    2018-05-29

    Factors that affect latent tuberculosis infection (LTBI) treatment completion in the US have not been well studied beyond public health settings. This gap was highlighted by recent health insurance-related regulatory changes that are likely to increase LTBI treatment by private sector healthcare providers. We analyzed LTBI treatment completion in the private healthcare setting to facilitate planning around this important opportunity for tuberculosis (TB) control in the US. We analyzed a national sample of commercial insurance medical and pharmacy claims data for people ages 0 to 64 years who initiated daily dose isoniazid treatment between July 2011 and March 2014 and who had complete data. All individuals resided in the US. Factors associated with treatment completion were examined using multivariable generalized ordered logit models and bivariate Kruskal-Wallis tests or Spearman correlations. We identified 1072 individuals with complete data who initiated isoniazid LTBI treatment. Treatment completion was significantly associated with less restrictive health insurance, age Private sector healthcare claims data provide insights into LTBI treatment completion patterns and patient/provider behaviors. Such information is critical to understanding the opportunities and limitations of private healthcare in the US to support treatment completion as this sector's role in protecting against and eliminating TB grows.

  8. Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting.

    Science.gov (United States)

    Sharma, Surendra K; Vashishtha, Richa; Chauhan, L S; Sreenivas, V; Seth, Divya

    2017-01-01

    There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings.

  9. Factors Associated with Noncompletion of Latent Tuberculosis Infection Treatment in an Inner-City Population in Edmonton, Alberta

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    Kathy Malejczyk

    2014-01-01

    Full Text Available A limited number of studies have been published that examine treatment completion rates and interventions used to increase treatment completion within an inner-city population. The purpose of the present study was to determine the rate of latent tuberculosis infection (LTBI treatment completion in an inner-city population in Edmonton, Alberta, and to identify factors that correlated with treatment completion. A retrospective chart review was conducted involving patients who started LTBI treatment between January 1, 2005 and December 31, 2010 in Edmonton’s inner city. A total of 77 patients started treatment and 57 (74% patients completed LTBI treatment. Homelessness was the only variable that was significantly associated with incomplete treatment (OR 8.0 [95% CI 1.4 to 45.6] and it remained significant when controlling for drug use (adjusted OR 6.5 [95% CI 1.1 to 38.8]. While the present study demonstrated treatment completion rates comparable with or better than those described in the general population, it highlighted the need for continued emphasis on interventions aimed at improving outcomes within homeless populations.

  10. A mathematical model for CTL effect on a latently infected cell inclusive HIV dynamics and treatment

    Science.gov (United States)

    Tarfulea, N. E.

    2017-10-01

    This paper investigates theoretically and numerically the effect of immune effectors, such as the cytotoxic lymphocyte (CTL), in modeling HIV pathogenesis (via a newly developed mathematical model); our results suggest the significant impact of the immune response on the control of the virus during primary infection. Qualitative aspects (including positivity, boundedness, stability, uncertainty, and sensitivity analysis) are addressed. Additionally, by introducing drug therapy, we analyze numerically the model to assess the effect of treatment consisting of a combination of several antiretroviral drugs. Our results show that the inclusion of the CTL compartment produces a higher rebound for an individual's healthy helper T-cell compartment than drug therapy alone. Furthermore, we quantitatively characterize successful drugs or drug combination scenarios.

  11. Acquired latent tuberculosis infection in psoriasis patients treated with etanercept in the People’s Republic of China

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    Li CR

    2015-10-01

    Full Text Available Cheng-Rang Li, Qiu-Xia Mao, Min Chen, Wei-Xue Jia, Xu Yao, Su-Ying Feng, Hong Jia, Juan-Qin Gong, Xue-Yuan Yang Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, People’s Republic of China Background: TNF-α plays a key role in host defense against mycobacterial infection, and patients receiving TNF-α blocker treatment have increased susceptibility to tuberculosis disease. In the People’s Republic of China, an intermediate tuberculosis-burden country, the latent tuberculosis infection (LTBI risk in patients with psoriasis who are treated with etanercept, the safest kind of TNF-α blocker, is unknown.Objectives: This study reports the LTBI risk in patients with psoriasis after etanercept treatment and aims to answer the question of how often rescreening for LTBI should be done in order to reduce active tuberculosis infection of patients and further reduce the incidence of active tuberculosis disease.Patients and methods: This retrospective review evaluated patients with moderate-to-severe chronic plaque psoriasis between 2009 and 2013. All patients were excluded tuberculosis infection and received etanercept 25 mg twice weekly, then the patients were checked for LTBI 3 months after etanercept treatment to observe the incidence of LTBI and assess the need for rescreening for LTBI every 3 months.Results: We retrospectively analyzed 192 patients with psoriasis with moderate-to-severe chronic plaque whose tuberculin skin test and chest X-rays were negative and who received etanercept 25 mg twice weekly. Eighteen of them were excluded because they received less than 3 months of etanercept therapy. After treatment with etanercept, four patients were found to have LTBI.Conclusion: In this study, the incidence of LTBI after 3 months was four in 192 (2.1%, which is higher than the annual incidence of LTBI in the People’s Republic of China (0.72%, so LTBI could be expected to occur

  12. Exosomes released in vitro from Epstein-Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs.

    Science.gov (United States)

    Canitano, Andrea; Venturi, Giulietta; Borghi, Martina; Ammendolia, Maria Grazia; Fais, Stefano

    2013-09-01

    EBV is a human herpesvirus associated with a number of malignancies. Both lymphoblastoid cell lines (LCLs), and EBV-infected nasopharyngeal carcinoma (NPC) cells have been demonstrated to release exosomes containing the EBV-encoded latent membrane protein 1 (LMP1), and mature micro-RNAs (EBV-miRNAs). Here we analyze the EBV protein and nucleic acid content of exosomes from different EBV-infected cells (LCL, 721 and Daudi) and we show for the first time that exosomes released from LCLs and 721 also contain EBV-encoded latent phase mRNAs. This confirms and strengthens exosomes pathogenetic potential, and might provide insights for development of novel diagnostic and therapeutic strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections.

    Science.gov (United States)

    O'Bryan, Joel M; Woda, Marcia; Co, Mary; Mathew, Anuja; Rothman, Alan L

    2013-08-26

    Declining telomere length (TL) is associated with T cell senescence. While TL in naïve and memory T cells declines with increasing age, there is limited data on TL dynamics in virus-specific memory CD4+ T cells in healthy adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL in T cells specific for several virus infections: non-recurring acute (vaccinia virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects. Additionally, five subjects provided multiple blood samples separated by up to 10 years. VACV- and CMV-specific T cells had longer average TL than IAV-specific CD4+ T cells. Although most virus-specific cells were CD45RA-, we observed a minor population of BrdU+ CD45RA+ T cells characterized by long telomeres. Longitudinal analysis demonstrated a slow decline in average TL in virus-specific T cells. However, in one subject, VZV reactivation led to an increase in average TL in VZV-specific memory T cells, suggesting a conversion of longer TL cells from the naïve T cell repertoire. TLs in memory CD4+ T cells in otherwise healthy adults are heterogeneous and follow distinct virus-specific kinetics. These findings suggests that the distribution of TL and the creation and maintenance of long TL memory T cells could be important for the persistence of long-lived T cell memory.

  14. Tuberculin skin test and interferon-gamma release assay values are associated with antimicrobial peptides expression in  polymorphonuclear cells during latent tuberculous infection

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    Julio E Castañeda-Delgado

    2014-06-01

    Full Text Available It has been reported that patients with progressive tuberculosis (TB express abundant amounts of the antimicrobial peptides (AMPs cathelicidin (LL-37 and human neutrophil peptide-1 (HNP-1 in circulating cells, whereas latent TB infected donors showed no differences when compared with purified protein derivative (PPD and QuantiFERON®-TB Gold (QFT-healthy individuals. The aim of this study was to determine whether LL-37 and HNP-1 production correlates with higher tuberculin skin test (TST and QFT values in TB household contacts. Twenty-six TB household contact individuals between 26-58 years old TST and QFT positive with at last two years of latent TB infection were recruited. AMPs production by polymorphonuclear cells was determined by flow cytometry and correlation between TST and QFT values was analysed. Our results showed that there is a positive correlation between levels of HNP-1 and LL-37 production with reactivity to TST and/or QFT levels. This preliminary study suggests the potential use of the expression levels of these peptides as biomarkers for progression in latent infected individuals.

  15. Epstein-Barr Virus (EBV) Latent Protein EBNA3A Directly Targets and Silences the STK39 Gene in B Cells Infected by EBV.

    Science.gov (United States)

    Bazot, Quentin; Paschos, Kostas; Allday, Martin J

    2018-04-01

    Epstein-Barr virus (EBV) establishes latent infection in human B cells and is associated with a wide range of cancers. The EBV nuclear antigen 3 (EBNA3) family proteins are critical for B cell transformation and function as transcriptional regulators. It is well established that EBNA3A and EBNA3C cooperate in the regulation of cellular genes. Here, we demonstrate that the gene STK39 is repressed only by EBNA3A. This is the first example of a gene regulated only by EBNA3A in EBV-transformed lymphoblastoid cell lines (LCLs) without the help of EBNA3C. This was demonstrated using a variety of LCLs carrying either knockout, revertant, or conditional EBNA3 recombinants. Investigating the kinetics of EBNA3A-mediated changes in STK39 expression showed that STK39 becomes derepressed quickly after EBNA3A inactivation. This derepression is reversible as EBNA3A reactivation represses STK39 in the same cells expressing a conditional EBNA3A. STK39 is silenced shortly after primary B cell infection by EBV, and no STK39 -encoded protein (SPAK) is detected 3 weeks postinfection. Chromatin immunoprecipitation (ChIP) analysis indicates that EBNA3A directly binds to a regulatory region downstream of the STK39 transcription start site. For the first time, we demonstrated that the polycomb repressive complex 2 with the deposition of the repressive mark H3K27me3 is not only important for the maintenance of an EBNA3A target gene ( STK39 ) but is also essential for the initial establishment of its silencing. Finally, we showed that DNA methyltransferases are involved in the EBNA3A-mediated repression of STK39 IMPORTANCE EBV is well known for its ability to transform B lymphocytes to continuously proliferating lymphoblastoid cell lines. This is achieved in part by the reprogramming of cellular gene transcription by EBV transcription factors, including the EBNA3 proteins that play a crucial role in this process. In the present study, we found that EBNA3A epigenetically silences STK39 This

  16. The Prevalence and Incidence of Latent Tuberculosis Infection and Its Associated Factors among Village Doctors in China.

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    Guangxue He

    Full Text Available China is a high tuberculosis (TB burden country. More than half of acute TB cases first seek medical care in village doctors' clinics or community health centers. Despite being responsible for patient referral and management, village doctors are not systematically evaluated for TB infection or disease. We assessed prevalence and incidence of latent TB infection (LTBI among village doctors in China.A longitudinal study was conducted in Inner Mongolia Autonomous Region. We administered a questionnaire on demographics and risk factors for TB exposure and disease; Tuberculin skin testing (TST and QuantiFERON-TB Gold in-tube assay (QFT-GIT was conducted at baseline and repeated 12 months later. We used a logistic regression model to calculate adjusted odds ratios (ORs for risk factors for TST and QFT-GIT prevalence and incidence. At the time of follow up, 19.5% of the 880 participating village doctors had a positive TST and 46.0% had a positive QFT-GIT result. Factors associated with TST prevalence included having a BCG scar (OR = 1.45, 95%CI 1.03-2.04 and smoking (OR = 1.69, 95%CI 1.17-2.44. Risk factors associated with QFT-GIT prevalence included being male (OR = 2.17, 95%CI 1.63-2.89, below college education (OR=1.42, 95%CI 1.01-1.97, and working for ≥25 years as a village doctor (OR = 1.64, 95%CI 1.12-2.39. The annual incidence of LTBI was 11.4% by TST and 19.1% by QFT-GIT. QFT-GIT conversion was associated with spending 15 minutes or more per patient on average (OR = 2.62, 95%CI 1.39-4.97 and having BCG scar (OR = 0.53, 95%CI 0.28-1.00.Prevalence and incidence of LTBI among Chinese village doctors is high. TB infection control measures should be strengthened among village doctors and at village healthcare settings.

  17. Risk of latent TB infection in individuals employed in the healthcare sector in Germany: a multicentre prevalence study

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    Harling Melanie

    2010-04-01

    Full Text Available Abstract Background Healthcare workers are still recognised as a high-risk group for latent TB infection (LTBI. Therefore, the screening of people employed in the healthcare sector for active and LTBI is fundamental to infection control programmes in German hospitals. It was the aim of the study to determine the prevalence and putative risk factors of LTBI. Methods We tested 2028 employees in the healthcare sector with the QuantiFERON-Gold In-tube (QFT-IT test between December 2005 and May 2009, either in the course of contact tracing or in serial testing of TB high-risk groups following German OSH legislation. Results A positive IGRA was found in 9.9% of the healthcare workers (HCWs. Nurses and physicians showed similar prevalence rates (9.7% to 9.6%. Analysed by occupational group, the highest prevalence was found in administration staff and ancillary nursing staff (17.4% and 16.7%. None of the individuals in the trainee group showed a positive IGRA result. In the different workplaces the observed prevalence was 14.7% in administration, 12.0% in geriatric care, 14.2% in technicians (radiology, laboratory and pathology, 6.5% in admission ward staff and 8.3% in the staff of pulmonary/infectious disease wards. Putative risk factors for LTBI were age (>55 years: OR14.7, 95% CI 5.1-42.1, being foreign-born (OR 1.99, 95% CI 1.4-2.8, TB in the individual's own history (OR 4.96, 95% CI 1.99-12.3 and previous positive TST results (OR 3.5, 95% CI 2.4-4.98. We observed no statistically significant association with gender, BCG vaccination, workplace or profession. Conclusion The prevalence of LTBI in low-incidence countries depends on age. We found no positive IGRA results among trainees in the healthcare sector. Incidence studies are needed to assess the infection risk. Pre-employment screening might be helpful in this endeavour.

  18. A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program.

    Science.gov (United States)

    Wingate, La'Marcus T; Coleman, Margaret S; de la Motte Hurst, Christopher; Semple, Marie; Zhou, Weigong; Cetron, Martin S; Painter, John A

    2015-12-01

    This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases

  19. Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Angel Descalzo, Miguel

    2007-06-15

    To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

  20. Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

    Directory of Open Access Journals (Sweden)

    Júlia Souza Vidal

    2015-10-01

    Full Text Available AbstractLatent tuberculosis infection (LTBI and human immunodeficiency virus (HIV-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

  1. The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

    Science.gov (United States)

    Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

    2011-01-01

    Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

  2. Aspectos virológicos e clínico-patológicos da infecção genital aguda e latente pelo herpesvírus bovino tipo 1.2 em bezerras infectadas experimentalmente Virological and clinico-pathological features of acute vulvovaginitis and latent infection by bovine herpesvirus 1.2 in heifers experimentally infected

    Directory of Open Access Journals (Sweden)

    Andréia Henzel

    2008-03-01

    and cows with bovine herpesvirus type 1.2 (BoHV-1.2 may result in vulvovaginitis and transient infertility. The acute infection is followed by the establishment of latent infection which can be periodically reactivated. We herein describe the virology and clinico-pathological aspects of acute and recrudescent vulvovaginitis in heifers inoculated with a Brazilian BoHV-1.2 isolate recovered from an outbreak of balanoposthitis. Genital inoculation of isolate SV-56/90 (10(8.1TCID50/animal in four eight-months-old heifers resulted in efficient virus replication in the genital mucosa and the development of moderate to severe vulvovaginitis. The inoculated heifers shed virus in genital secretions in titers up to 10(7.3TCID50/mL until day 10 pi and developed genital congestion, swelling, vesicles and pustules. The vesicles and pustules increased in size eventually coalesced and became covered with a yellowish exsudate. These signs appeared at day 2 pi, increased in severity up to days 5 - 8 pi and progressively subsided thereafter. Dexamethasone administration at day 55 pi resulted in virus shedding in vaginal secretions for up to 10 days. Virus reactivation in all animals was accompanied by clinical recrudescence of the disease, yet less severe than during acute infection. Examination of sacral ganglia and lymph nodes by PCR at day 36 post-reactivation revealed the presence of latent viral DNA in the pudendal (4/4, genito-femoral, sciatic and rectal caudal (3/4 and obturator nerve ganglia (1/4; in addition to several regional lymph nodes. These results demonstrate the virulence of isolate SV-56/90 for heifers and pave the way for its use in further pathogenesis studies and vaccine-challenge trials.

  3. Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals

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    Catherine Riou

    2017-08-01

    Full Text Available Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB. However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1, activation (HLA-DR, homing potential (CCR4, CCR6, CXCR3, and CD161 and functional profiles (IFNγ, IL-2, and TNFα of Mycobacterium tuberculosis (Mtb-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC = 0.92, 95% CI: 0.82–1.01, specificity: 82%, sensitivity: 84% for HIV− and AUC = 0.99, 95% CI: 0.98–1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB.

  4. Chromatin Structure of Epstein-Barr Virus Latent Episomes.

    Science.gov (United States)

    Lieberman, Paul M

    2015-01-01

    EBV latent infection is characterized by a highly restricted pattern of viral gene expression. EBV can establish latent infections in multiple different tissue types with remarkable variation and plasticity in viral transcription and replication. During latency, the viral genome persists as a multi-copy episome, a non-integrated-closed circular DNA with nucleosome structure similar to cellular chromosomes. Chromatin assembly and histone modifications contribute to the regulation of viral gene expression, DNA replication, and episome persistence during latency. This review focuses on how EBV latency is regulated by chromatin and its associated processes.

  5. Cell-mediated immunity in herpes simplex virus-infected mice: functional analysis of lymph node cells during periods of acute and latent infection, with reference to cytotoxic and memory cells.

    Science.gov (United States)

    Nash, A A; Quartey-Papafio, R; Wildy, P

    1980-08-01

    The functional characteristics of lymphoid cells were investigated during acute and latent infection of mice with herpes simplex virus (HSV). Cytotoxic T cells were found in the draining lymph node (DLN) 4 days p.i. and had reached maximum activity between 6 and 9 days. After the 12th day and during the period of latent infection (> 20 days) no cytotoxic cell activity was observed. Cytotoxic activity could only be detected when the lymphoid cells had been cultured for a period of 3 days. In general, the cell killing was specific for syngeneic infected target cells, although some killing of uninfected targets was observed. In contrast to the cytotoxic response, DLN cells responding to HSV in a proliferation assay were detected towards the end of the acute phase and at lease up to 9 months thereafter. The significance of these observations for the pathogenesis of HSV is discussed.

  6. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

    Science.gov (United States)

    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  7. Emergence of CD4+ and CD8+ Polyfunctional T Cell Responses Against Immunodominant Lytic and Latent EBV Antigens in Children With Primary EBV Infection

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    Janice K. P. Lam

    2018-03-01

    Full Text Available Long term carriers were shown to generate robust polyfunctional T cell (PFC responses against lytic and latent antigens of Epstein-Barr virus (EBV. However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM] and asymptomatic (AS EBV infection. Evaluation of IFN-γ secreting CD8+ T cell responses upon stimulation by HLA class I-specific peptides of EBV lytic and latent proteins by ELISPOT assay followed by assessment of CD4+ and CD8+ PFC responses upon stimulation by a panel of overlapping EBV peptides for co-expression of IFN-γ, TNF-α, IL-2, perforin and CD107a by flow cytometry were performed. Cytotoxicity of T cells against autologous lymphoblastoid cell lines (LCLs as well as EBV loads in PBMC and plasma were also determined. Both IM and AS patients had elevated PBMC and plasma viral loads which declined steadily during a 12-month period from the time of diagnosis whilst decrease in the magnitude of CD8+ T cell responses toward EBV lytic peptides in contrast to increase toward latent peptides was shown with no significant difference between those of IM and AS patients. Both lytic and latent antigen-specific CD4+ and CD8+ T cells demonstrated polyfunctionality (defined as greater or equal to three functions concurrent with enhanced cytotoxicity against autologous LCLs and steady decrease in plasma and PBMC viral loads over time. Immunodominant peptides derived from BZLF1, BRLF1, BMLF1 and EBNA3A-C proteins induced the highest proportion of CD8+ as well as CD4+ PFC responses. Diverse functional subtypes of both CD4+ and CD8+ PFCs were shown to emerge at 6–12 months. In conclusion, EBV antigen-specific CD4+ and CD

  8. Targeted photodynamic therapy of established soft-tissue infections in mice

    Science.gov (United States)

    Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

    2004-06-01

    The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to resistant soft-tissue infections.

  9. Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection

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    Pilar Alberdi

    2016-07-01

    Full Text Available Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis and establish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.

  10. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract.

    Science.gov (United States)

    Koenigsknecht, Mark J; Theriot, Casey M; Bergin, Ingrid L; Schumacher, Cassie A; Schloss, Patrick D; Young, Vincent B

    2015-03-01

    Clostridium difficile infection (CDI) following antibiotic therapy is a major public health threat. While antibiotic disruption of the indigenous microbiota underlies the majority of cases of CDI, the early dynamics of infection in the disturbed intestinal ecosystem are poorly characterized. This study defines the dynamics of infection with C. difficile strain VPI 10463 throughout the gastrointestinal (GI) tract using a murine model of infection. After inducing susceptibility to C. difficile colonization via antibiotic administration, we followed the dynamics of spore germination, colonization, sporulation, toxin activity, and disease progression throughout the GI tract. C. difficile spores were able to germinate within 6 h postchallenge, resulting in the establishment of vegetative bacteria in the distal GI tract. Spores and cytotoxin activity were detected by 24 h postchallenge, and histopathologic colitis developed by 30 h. Within 36 h, all infected mice succumbed to infection. We correlated the establishment of infection with changes in the microbiota and bile acid profile of the small and large intestines. Antibiotic administration resulted in significant changes to the microbiota in the small and large intestines, as well as a significant shift in the abundance of primary and secondary bile acids. Ex vivo analysis suggested the small intestine as the site of spore germination. This study provides an integrated understanding of the timing and location of the events surrounding C. difficile colonization and identifies potential targets for the development of new therapeutic strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia.

    Directory of Open Access Journals (Sweden)

    Monique van Velzen

    2013-08-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection results in lifelong chronic infection of trigeminal ganglion (TG neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates.

  12. A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by prunus necrotic ringspot virus and peach latent mosaic viroid.

    Science.gov (United States)

    Herranz, Mari Carmen; Niehl, Annette; Rosales, Marlene; Fiore, Nicola; Zamorano, Alan; Granell, Antonio; Pallas, Vicente

    2013-05-28

    Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in

  13. Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts.

    Science.gov (United States)

    Tuchscherr, Lorena; Korpos, Èva; van de Vyver, Hélène; Findeisen, Clais; Kherkheulidze, Salome; Siegmund, Anke; Deinhardt-Emmer, Stefanie; Bach, Olaf; Rindert, Martin; Mellmann, Alexander; Sunderkötter, Cord; Peters, Georg; Sorokin, Lydia; Löffler, Bettina

    2018-05-22

    Staphylococcus aureus is the most frequent pathogen causing diabetic foot infections. Here, we investigated the degree of bacterial virulence required to establish invasive tissue infections in diabetic organisms. Staphylococcal isolates from diabetic and non-diabetic foot ulcers were tested for their virulence in in vitro functional assays of host cell invasion and cytotoxicity. Isolates from diabetes mellitus type I/II patients exhibited less virulence than isolates from non-diabetic patients, but were nevertheless able to establish severe infections. In some cases, non-invasive isolates were detected deep within diabetic wounds, even though the strains were non-pathogenic in cell culture models. Testing of defined isolates in murine footpad injection models revealed that both low- and high-virulent bacterial strains persisted in higher numbers in diabetic compared to non-diabetic hosts, suggesting that hyperglycemia favors bacterial survival. Additionally, the bacterial load was higher in NOD mice, which have a compromised immune system, compared to C57Bl/6 mice. Our results reveal that high as well as low-virulent staphylococcal strains are able to cause soft tissue infections and to persist in diabetic humans and mice, suggesting a reason for the frequent and endangering infections in patients with diabetes. Copyright © 2018 Elsevier GmbH. All rights reserved.

  14. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

    Science.gov (United States)

    Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

    2013-10-24

    The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus

  15. [Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

    Science.gov (United States)

    Chen, Y S; Lin, X H; Li, H R; Hua, Z D; Lin, M Q; Huang, W S; Yu, T; Lyu, H Y; Mao, W P; Liang, Y Q; Peng, X R; Chen, S J; Zheng, H; Lian, S Q; Hu, X L; Yao, X Q

    2017-12-12

    Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the

  16. The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis

    DEFF Research Database (Denmark)

    Snygg-Martin, Ulrika; Rasmussen, Rasmus Vedby; Hassager, Christian

    2011-01-01

    Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate....

  17. Establishment of a Pcr Technique for Determination of Htlv-1 Infection in Paraffin-Embedded Tissues

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    M Rastin

    2007-04-01

    Full Text Available Introduction: HTLV-1 , the first known human retrovirus belongs to oncovirus subfamily of retroviruses. The major characteristic of HTLV-1 is its highly restricted geographic prevalence. Northern part of Khorasan is an endemic region of HTLV-1 infection. Epidemiological studies can help in designing preventive programs for HTLV-1 infection. The aim of this study was the establishment of a PCR technique for determination of HTLV-1 infection in paraffin-embedded tissues. Methods: In this experimental laboratory study for establishment of a technique, PCR was initially optimized using Beta-actin primers on various formalin fixed paraffin-embedded tissues from liver, spleen, skin and lymph nodes. The optimized concentration of Mgcl2 was 2mm, primer was 8 pmol. Optimized concentration of DNA was different according to the kind of tissue. HTLV-1 infection was determined by applying tax, pol, env and LTR primers on 50 paraffin-embedded lymph node tissues . The reporoducibility of this technique was shown for skin and lymph node tissues infected with HTLV-1. Resuls: In 50 lymph node tissues, one case with pathologic diagnosis of NHL was positive with all 5 sets of primers (tax, Pol, env and LTR primers and the other case was positive with only two sets of tax primers but was negative with pol, env and LTR primers. The prevalence of infection was 2% among lymph node specimens. (1 of 50 specimens and if the second case is considered, the prevalence would be 4%. Conclusion: Comparison of the results of this study with another study on blood specimens (seroprevalence2.3% was not statistically significant thus confirming the results of one another. (P=0.883

  18. Effects of Samorin Treatment and Delayed Infection on the Establishment of Trypanosomes in Glossina Pallidipes

    Energy Technology Data Exchange (ETDEWEB)

    Okoth, S; Mukiria, P; Tinega, G; Murilla, G [Trypanosomiasis Research Centre, Kenya Agricultural Research Institute (TRC-KARI), Box 362, Kikuyu (Kenya)

    2012-07-15

    The protective role of Samorin (isometamidium chloride) when given with the bloodmeal, and the effect of the age of flies at infective feed, on the establishment of Trypanosoma congolense and Trypanosoma vivax in Glossina pallidipes Austen was evaluated. G. pallidipes was fed on fresh bovine blood containing 0, 6, 8, 10, 12 and 14 {mu}g of Samorin/mL of blood on day 0. A control group was fed in vivo on an infected goat as first feed on the same day (day 0). On day 3 post-Samorin treatment, the flies were infected in vivo by feeding them on a goat infected with either T. congolense or T. vivax. Similar procedures were followed for the experimental groups infected 5, 10 and 20 days post-Samorin treatment. Thereafter flies were maintained on rabbits for 15 and 20 days for the T. vivax and T. congolense groups, respectively. Fly survival was assessed, and the flies were dissected to determine infection rates. Results showed that the age of a fly at infection significantly affected the refractoriness of G. pallidipes to T. congolense ( F{sub 4,20} = 5.241; P=0.0047) and T. vivax ( F{sub 4,20} = 5.410; P=0.0040) infections. However, the effect of Samorin treatment on infection per se was not shown to be significant (F{sub 5,19} = 2.383; P=0733 and F{sub 4,20} = 1.106; P=0.3900) for T. congolense and T. vivax, respectively. The age of flies at infection significantly reduced tsetse survival (F{sub 4,20} = 7.584; P<0.001 and F{sub 4,20} = 10.755; P=0.0001) for T. congolense and T. vivax groups, respectively. However, Samorin treatment did not significantly reduce survival in both Trypanosoma groups (F{sub 5,19} = 0.642; P>0.67 and F{sub 5,19} = 0.485; P=0.783). These results indicated that, for T. congolense and T. vivax, combining Samorin treatment at a concentration of at least 8 {mu}g/mL, and delaying exposure of tsetse to infective feed for at least 3 days post emergence, induces sufficient refractoriness that may counter the increased challenge posed by the mass

  19. α4β7+ CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection.

    Science.gov (United States)

    Cheung, Ka-Wai; Wu, Tongjin; Ho, Sai Fan; Wong, Yik Chun; Liu, Li; Wang, Hui; Chen, Zhiwei

    2018-04-15

    HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α 4 β 7 + gut-homing CCR7 - CD4 + effector/effector memory T cells (T EM ) and results in massive depletion of these cells and other subsets of T EM in gut-associated lymphoid tissues. However, besides being eliminated by HIV-1, the role of T EM during the early stage of infection remains inconclusive. Here, using in vitro -induced α 4 β 7 + gut-homing T EM (α 4 β 7 + T EM ), we found that α 4 β 7 + T EM differentiated into CCR7 + CD4 + central memory T cells (T CM ). This differentiation was HIV-1 independent but was inhibited by SB431542, a specific transforming growth factor β (TGF-β) receptor I kinase inhibitor. Consistently, T EM -to-T CM differentiation was observed in α 4 β 7 + T EM stimulated with TGF-β1 (TGF-β). The T CM properties of the TGF-β-induced T EM -derived T CM (α 4 β 7 + T CM ) were confirmed by their enhanced CCL19 chemotaxis and the downregulation of surface CCR7 upon T cell activation in vitro Importantly, the effect of TGF-β on T CM differentiation also held in T EM directly isolated from peripheral blood. To investigate the significance of the TGF-β-dependent T EM -to-T CM differentiation in HIV/AIDS pathogenesis, we observed that both productively and latently infected α 4 β 7 + T CM could differentiate from α 4 β 7 + T EM in the presence of TGF-β during HIV-1 infection. Collectively, this study not only provides a new insight for the plasticity of T EM but also suggests that the TGF-β-dependent T EM -to-T CM differentiation is a previously unrecognized mechanism for the formation of latently infected T CM after HIV-1 infection. IMPORTANCE HIV-1 is the causative agent of HIV/AIDS, which has led to millions of deaths in the past 30 years. Although the implementation of highly active antiretroviral therapy has remarkably reduced the HIV-1-related morbidity and mortality, HIV-1 is not eradicated in

  20. Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

    Science.gov (United States)

    Kerrigan, Deanna; Tudor, Carrie; Motlhaoleng, Katlego; Lebina, Limakatso; Qomfu, Cokiswa; Variava, Ebrahim; Chon, Sandy; Martinson, Neil; Golub, Jonathan E

    2018-04-16

    Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

  1. CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals.

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    Alejandra Pera

    Full Text Available Cytomegalovirus (CMV latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality rather than with quantity (percentage of T cells. We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a, IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB. Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells

  2. The Ozobranchus leech is a candidate mechanical vector for the fibropapilloma-associated turtle herpesvirus found latently infecting skin tumors on Hawaiian green turtles (Chelonia mydas)

    International Nuclear Information System (INIS)

    Greenblatt, Rebecca J.; Work, Thierry M.; Balazs, George H.; Sutton, Claudia A.; Casey, Rufina N.; Casey, James W.

    2004-01-01

    Fibropapillomatosis (FP) of marine turtles is a neoplastic disease of ecological concern. A fibropapilloma-associated turtle herpesvirus (FPTHV) is consistently present, usually at loads exceeding one virus copy per tumor cell. DNA from an array of parasites of green turtles (Chelonia mydas) was examined with quantitative PCR (qPCR) to determine whether any carried viral loads are sufficient to implicate them as vectors for FPTHV. Marine leeches (Ozobranchus spp.) were found to carry high viral DNA loads; some samples approached 10 million copies per leech. Isopycnic sucrose density gradient/qPCR analysis confirmed that some of these copies were associated with particles of the density of enveloped viruses. The data implicate the marine leech Ozobranchus as a mechanical vector for FPTHV. Quantitative RT-PCR analysis of FPTHV gene expression indicated that most of the FPTHV copies in a fibropapilloma have restricted DNA polymerase expression, suggestive of latent infection

  3. Retroviral DNA--the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats.

    Science.gov (United States)

    Nesina, Stefanie; Katrin Helfer-Hungerbuehler, A; Riond, Barbara; Boretti, Felicitas S; Willi, Barbara; Meli, Marina L; Grest, Paula; Hofmann-Lehmann, Regina

    2015-12-21

    veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered.

  4. Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.

    Science.gov (United States)

    Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L

    2016-01-01

    Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4-5 days earlier.

  5. Identification and characterization of the SSB1 locus involved in symptom development by Spring beauty latent virus infection in Arabidopsis thaliana.

    Science.gov (United States)

    Fujisaki, Koki; Hagihara, Fumi; Azukawa, Yoshihiro; Kaido, Masanori; Okuno, Tetsuro; Mise, Kazuyuki

    2004-09-01

    The natural variation of Arabidopsis thaliana in response to a bromovirus, Spring beauty latent virus (SBLV), was examined. Of 63 Arabidopsis accessions tested, all were susceptible when inoculated with SBLV, although there was a large degree of variation in symptom development. Most accessions, including Columbia (Col-0), were symptomless or developed only mild symptoms, but four accessions, including S96, showed severe symptoms of SBLV infection. Genetic analysis suggested that the difference in the responses of Col-0 and S96 to SBLV was controlled by a single semidominant locus. We have designated this locus SSB1 (symptom development by SBLV infection). By using genetic markers, SSB1 was mapped to chromosome IV. The patterns of distribution and accumulation of SBLV in sensitive accessions were similar to those in the insensitive accessions. In addition, symptom development in S96 by SBLV infection was critically interrupted by the presence of the NahG gene, which encodes salicylic acid (SA) hydroxylase. These data suggest that symptom development in A. thaliana controlled by SSB1 is independent of the efficiency of SBLV multiplication and is dependent on SA signaling.

  6. Role of latent membrane protein 1 in chronic active Epstein–Barr virus infection-derived T/NK-cell proliferation

    International Nuclear Information System (INIS)

    Ito, Takuto; Kawazu, Hidetaka; Murata, Takayuki; Iwata, Seiko; Arakawa, Saki; Sato, Yoshitaka; Kuzushima, Kiyotaka; Goshima, Fumi; Kimura, Hiroshi

    2014-01-01

    Epstein–Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line

  7. Effect of age and latent CMV infection on CD8+ CD56+ T cells (NKT-like) frequency and functionality.

    Science.gov (United States)

    Hassouneh, Fakhri; Campos, Carmen; López-Sejas, Nelson; Alonso, Corona; Tarazona, Raquel; Solana, Rafael; Pera, Alejandra

    2016-09-01

    Changes in the T cell pool caused by CMV infection have been proposed to contribute to immunosenescence, but it has been postulated that CMV can also have some beneficial effects in young individuals improving the immune response to other pathogens. T cells expressing CD56 (NKT-like cells) are cytotoxic effector cells with a significant role in the immune response against cancer. We have studied how age and latent CMV infection affect the frequency of NKT-like cells (CD8+ CD56+ T cells) and their response to Staphylococcal Enterotoxin B (SEB) in the context of CMV and ageing. NKT-like cell percentage increases with the combination of both CMV and age. The response to SEB and the polyfunctional index of NKT-like cells also increase with age in CMV-seropositive individuals. In young individuals, CMV infection induces a shift on the polyfunctional profile of CD8+ CD56- T cells not observed on the NKT-like cells response. NKT-like cells expressing CD57 are expanded in CMV-seropositive individuals and are more polyfunctional than their CD57-  counterpart. In addition CD57- NKT-like cells are more polyfunctional than CD8+ CD56- CD57- T cells. The results support that the expansion of polyfunctional NKT-cells may have a beneficial effect on the immune response against pathogens. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Use of IFN-γ and IP-10 detection in the diagnosis of latent tuberculosis infection in patients with inflammatory rheumatic diseases.

    Science.gov (United States)

    Villar-Hernández, Raquel; Latorre, Irene; Mínguez, Sonia; Díaz, Jéssica; García-García, Esther; Muriel-Moreno, Beatriz; Lacoma, Alicia; Prat, Cristina; Olivé, Alex; Ruhwald, Morten; Mateo, Lourdes; Domínguez, José

    2017-10-01

    Biologic agents are used against rheumatic diseases, however, they increase the risk of developing severe infections and diseases such as tuberculosis. We aimed to determine the benefits of IP-10 detection to diagnose latent tuberculosis infection (LTBI) in patients with inflammatory rheumatic diseases on different immunosuppressive drug regimens, and compare these results with IFN-γ detection. We included 64 patients with inflammatory rheumatic diseases. We used QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB to detect IFN-γ production, and an in-house ELISA for IP-10 detection from the previous QFN-G-IT stimulated samples. We assessed the combined use of IFN-γ release assays (IGRAs) and IP-10 test, and analyzed the influence of immunotherapy on the tests performance. We obtained 34.9% positive results by T-SPOT.TB, 25.0% by QFN-G-IT and 31.3% by IP-10 test. The combined use of IGRAs and IP-10 detection increased significantly the amount of positive results (p  0.05). IP-10 and IFN-γ detection is comparable and their combined use could increase the number of positive results in the diagnosis of LTBI in rheumatic patients. The tested assays were not influenced by rheumatoid immunosuppressive therapy. Thus, IP-10 could be of use in the development of new and improved LTBI diagnostic tools. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  9. Identification of latent tuberculosis infection-related microRNAs in human U937 macrophages expressing Mycobacterium tuberculosis Hsp16.3.

    Science.gov (United States)

    Meng, Qing-Lin; Liu, Fei; Yang, Xing-Yuan; Liu, Xiao-Mei; Zhang, Xia; Zhang, Chun; Zhang, Zong-De

    2014-02-12

    Latent tuberculosis infection (LTBI) relies on a homeostasis of macrophages and Mycobacterium tuberculosis (Mtb). The small heat shock protein, Mtb Hsp16.3 (also known as latency-associated antigen), plays an important role in Mtb persistence within macrophages. However, the mechanism of LTBI remains elusive. The aim of this study was to delineate LTBI-related miRNA expression in U937 macrophages expressing Mtb Hsp16.3 protein. U937 macrophages were infected with an integrase-deficient Lentivirus vector to transiently express Mtb Hsp16.3, and green fluorescent protein (GFP) as a control. We used a microRNA (miRNA) microarray chip containing more than 1000 probes to identify the significant differentially expressed miRNAs in the infected U937 cells, and employed real-time quantitative polymerase chain reaction (qRT-PCR) for validation. Furthermore, we confirmed these candidate LTBI-related miRNAs in peripheral blood mononuclear cells from subjects with LTBI and in healthy control individuals. Functional annotation prediction of miRNA target genes and pathway enrichment analyses were used to explore the putative links between these miRNAs and LTBI. Analysis of the miRNA expression profile identified 149 miRNAs that were differentially expressed in U937 macrophages expressing Mtb Hsp16.3 compared with the control expressing GFP. The expression level of seven miRNAs (miR-424-5p, miR-493-5p, miR-296-5p, miR-27b-3p, miR-377-5p, miR-3680-5p, miR-191-5p) were validated by qRT-PCR. The expression level of four miRNAs (miR-424-5p, miR-27b-3p, miR-377-5p, miR-3680-5p) in the peripheral blood mononuclear cells samples from LTBI and healthy participants reflected the altered patterns observed in the microarray profile. The bioinformatic analyses suggest that the miRNAs may regulate Mtb latent infection by affecting the development of macrophage cells. The results suggest that miRNA expression may play a considerable role in the pathogenesis of LTBI, and this would increase our

  10. 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

  11. Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.

    Science.gov (United States)

    Kotani, Osamu; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Sato, Yuko; Nakajima, Noriko; Koike, Satoshi; Iwasaki, Takuya; Sata, Tetsutaro; Yamashita, Teruo; Minagawa, Hiroko; Taguchi, Fumihiro; Hasegawa, Hideki; Shimizu, Hiroyuki; Nagata, Noriyo

    2015-04-01

    The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross-reacted with non-enteroviruses within the family Picornaviridae. However, all cross-reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non-structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally-infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in-house anti-enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different

  12. Prevalence of cutipositivity in a sample of homeless shelter population in Rome in the course of Latent Tuberculosis Infection surveillance plan. Preliminary results

    Directory of Open Access Journals (Sweden)

    Patrizia Laurenti

    2010-03-01

    Full Text Available

    Background: in Europe homelessness is a known risk factor both for active and latent tuberculosis (TB. In Rome 409 cases of TB were notified in 2004, but the real occurrence among homeless people is unknown. Tuberculosis surveillance has been organized with the aim to develop an integrated model for the risk evaluation and management of both Latent Tuberculosis infections (LTBI and TB in Rome homeless people.

    Methods: the eligible individuals have been recruited in the homeless’ refuges. The Tuberculin Mantoux test has been used to evaluate the infection prevalence; in case of a positive result, the individual’s expectorate has been collected and the chest X-ray has been performed. A collecting data form has been filled in for evaluating some risk factors. Multiple logistic regression models have been carried out to find statistically significant determinants of infection.

    Results: out of 120 subjects recruited, 108 came back for the evaluation of the skin test; the prevalence of LTBI was 43.5% (47/108 subjects; no active TB cases were found. According to the multivariate analysis, factors significantly associated to LTBI are gender (for males OR = 4.94; 95% CI: 1.46 – 16.67, 1st model; OR 5.84; 95% CI: 1.26 – 21.10, 2nd model, birth place (for Europe: OR 3.05; 95% CI: 1.02 – 9.13, 1st model; OR 3.12; 95% CI: 1.10 – 8.88, 2nd model; for East Mediterranean native Region OR = 4.34; 95%CI: 1.15-16.39; Body Mass Index class (for obesity OR = 3.34; 95% CI:1.31-8.51.

    Conclusions: these preliminary results have demonstrated a high prevalence of LTBI among homeless people. Male gender, birth place (Europe and East Mediterranean native Region and obesity were found to be significant risk factors. The surveillance system allowed positive patients for LTBI to be rapidly directed to a specialized centre for the clinical evaluation and the appropriate therapy

  13. Prevalence and Treatment of Latent Tuberculosis Infection Among Newly Arrived Refugees in San Diego County, January 2010–October 2012

    Science.gov (United States)

    Bennett, Rachel J.; Brodine, Stephanie; Waalen, Jill; Moser, Kathleen; Rodwell, Timothy C.

    2014-01-01

    Objectives. We determined the prevalence and treatment rates of latent tuberculosis infection (LTBI) in newly arrived refugees in San Diego County, California, and assessed demographic and clinical characteristics associated with these outcomes. Methods. We analyzed data from LTBI screening results of 4280 refugees resettled in San Diego County between January 2010 and October 2012. Using multivariate logistic regression, we calculated the associations between demographic and clinical risk factors and the outcomes of LTBI diagnosis and LTBI treatment initiation. Results. The prevalence of LTBI was highest among refugees from sub-Saharan Africa (43%) and was associated with current smoking and having a clinical comorbidity that increases the risk for active tuberculosis. Although refugees from sub-Saharan Africa had the highest prevalence of infection, they were significantly less likely to initiate treatment than refugees from the Middle East. Refugees with postsecondary education were significantly more likely to initiate LTBI treatment. Conclusions. Public health strategies are needed to increase treatment rates among high-risk refugees with LTBI. Particular attention is required among refugees from sub-Saharan Africa and those with less education. PMID:24524534

  14. Prevalencia de infección tuberculosa latente en población inmigrante que ingresa en prisión Prevalence of latent tuberculosis infection amongst immigrants entering prison

    Directory of Open Access Journals (Sweden)

    N. Solé

    2012-06-01

    Full Text Available Objetivo: Estudiar la prevalencia de infección tuberculosa latente (ITL y sus factores predictivos en población reclusa inmigrante. Métodos: Estudio prospectivo realizado en mayo y junio de 2009. Se realizó intradermorreacción de Mantoux (IDRM, considerándose positiva la induración ≥ 10 mm. Se recogen las variables: edad, origen, reincidencia, tiempo en España, consumo de heroína y/o cocaína, uso de drogas intravenosas e infección VIH. Se calcula la tasa de ITL y la tasa global de infección (ITL más antecedente de tuberculosis. Para estudiar factores predictivos, se realizó un análisis bivariante y multivariante mediante regresión logística. Resultados: Se estudiaron 152 varones inmigrantes al ingreso en prisión. Edad media: 31,9 años ± 7,8. El 37,3% consumidor de heroína y/o cocaína y el 7,5% usuarios de drogas por vía intravenosa (UDI. 12 tenían IDRM previa positiva y 6 antecedente de TB. Se realizó IDRM a 134, 63 con resultado positivo y 71 con resultado negativo. Tasa de ITL: 49,3%. Tasa global de infección: 53,3%. Bivariadamente, se asoció a la ITL: la reincidencia (67,4% vs 36,4% en primarios, p=0,001, la edad (76% en los ≥ 40 años vs 40,4% en menores de esa edad; p=0,002 y el consumo de heroína y/o cocaína (60% en consumidores vs 39,3% en no consumidores; p= 0,02. El análisis multivariante sólo confirmó la asociación con la edad (p=0,001; OR: 2,34, IC= 1,39-3,94. Conclusiones: La tasa de ITL en inmigrantes que ingresan en prisión es muy elevada. Se recomienda en todos un completo estudio, con especial dedicación a los más vulnerables como los inmigrantes de mayor edad.Objective: To study the prevalence of latent tuberculosis infection (LTBI and the predictive factors amongst immigrants entering prison. Methods: prospective study conducted in May and June of 2009. The tuberculin skin test (TST was performed, with induration of ≥ 10 mm being regarded as positive. Variables collected were: age

  15. Development of a method for detection of latent European fruit tree canker (Neonectria ditissima) infections in apple and pear nurseries

    NARCIS (Netherlands)

    Wenneker, Marcel; Jong, de Peter F.; Joosten, Nina N.; Goedhart, Paul W.; Thomma, Bart P.H.J.

    2017-01-01

    Fruit tree canker caused by Neonectria ditissima is a serious problem in apple-producing regions with moderate temperatures and high rainfall throughout the year; especially in northwestern Europe, Chile, and New Zealand. Control measures are applied to protect primary infection sites, mainly leaf

  16. Characterization of Chemokine Receptor Utilization of Viruses in the Latent Reservoir for Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Pierson, Theodore; Hoffman, Trevor L.; Blankson, Joel; Finzi, Diana; Chadwick, Karen; Margolick, Joseph B.; Buck, Christopher; Siliciano, Janet D.; Doms, Robert W.; Siliciano, Robert F.

    2000-01-01

    Latently infected resting CD4+ T cells provide a long-term reservoir for human immunodeficiency virus type 1 (HIV-1) and are likely to represent the major barrier to virus eradication in patients on combination antiretroviral therapy. The mechanisms by which viruses enter the latent reservoir and the nature of the chemokine receptors involved have not been determined. To evaluate the phenotype of the virus in this compartment with respect to chemokine receptor utilization, full-length HIV-1 env genes were cloned from latently infected cells and assayed functionally. We demonstrate that the majority of the viruses in the latent reservoir utilize CCR5 during entry, although utilization of several other receptors, including CXCR4, was observed. No alternative coreceptors were shown to be involved in a systematic fashion. Although R5 viruses are present in the latent reservoir, CCR5 was not expressed at high levels on resting CD4+ T cells. To understand the mechanism by which R5 viruses enter latent reservoir, the ability of an R5 virus, HIV-1 Ba-L, to infect highly purified resting CD4+ T lymphocytes from uninfected donors was evaluated. Entry of Ba-L could be observed when virus was applied at a multiplicity approaching 1. However, infection was limited to a subset of cells expressing low levels of CCR5 and markers of immunologic memory. Naive cells could not be infected by an R5 virus even when challenged with a large inoculum. Direct cell fractionation studies showed that latent virus is present predominantly in resting memory cells but also at lower levels in resting naive cells. Taken together, these findings provide support for the hypothesis that the direct infection of naive T cells is not the major mechanism by which the latent infection of resting T cells is established. PMID:10933689

  17. The host cell sulfonation pathway contributes to retroviral infection at a step coincident with provirus establishment.

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    James W Bruce

    2008-11-01

    Full Text Available The early steps of retrovirus replication leading up to provirus establishment are highly dependent on cellular processes and represent a time when the virus is particularly vulnerable to antivirals and host defense mechanisms. However, the roles played by cellular factors are only partially understood. To identify cellular processes that participate in these critical steps, we employed a high volume screening of insertionally mutagenized somatic cells using a murine leukemia virus (MLV vector. This approach identified a role for 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1, one of two enzymes that synthesize PAPS, the high energy sulfate donor used in all sulfonation reactions catalyzed by cellular sulfotransferases. The role of the cellular sulfonation pathway was confirmed using chemical inhibitors of PAPS synthases and cellular sulfotransferases. The requirement for sulfonation was mapped to a stage during or shortly after MLV provirus establishment and influenced subsequent gene expression from the viral long terminal repeat (LTR promoter. Infection of cells by an HIV vector was also shown to be highly dependent on the cellular sulfonation pathway. These studies have uncovered a heretofore unknown regulatory step of retroviral replication, have defined a new biological function for sulfonation in nuclear gene expression, and provide a potentially valuable new target for HIV/AIDS therapy.

  18. First report of latent infection of Cyperus rotundus caused by a biovar 3 Dickeya sp. (Syn. Erwinia chrysanthemi) in Israel

    NARCIS (Netherlands)

    Tsror, L.; Lebiush, S.; Erlich, O.; Ben-Daniel, B.; Wolf, van der J.M.

    2010-01-01

    Recent outbreaks of potato blackleg in Israel, caused by Dickeya spp., on plants grown from seed tubers imported from Northern Europe, are of a great concern. The warm climatic conditions during the growing season favour disease expression, and may result in the establishment of the pathogen in the

  19. Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence

    Science.gov (United States)

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants. PMID:24659872

  20. Establishment of chronic hepatitis C virus infection: translational evasion of oxidative defence.

    Science.gov (United States)

    Chan, Shiu-Wan

    2014-03-21

    Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants.

  1. Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus.

    Science.gov (United States)

    Martín, Verónica; Mavian, Carla; López Bueno, Alberto; de Molina, Antonio; Díaz, Eduardo; Andrés, Germán; Alcami, Antonio; Alejo, Alí

    2015-10-01

    Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Ethiopia's experience on scaling up latent TB infection management for people living with HIV and under-five child household contacts of index TB patients

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    Blen Ayele Kebede

    2018-01-01

    Full Text Available Management of latent tuberculosis infection (LTBI is one of the globally recommended key strategies to end tuberculosis. However, there is limited experience with translation of global recommendations into action at country levels. We present Ethiopia's experience in implementing LTBI management. Our objective is to share promising practices, existing opportunities and to suggest specific steps required for further scale up of the services. Our report is based on synthesis of data from secondary sources including official routine reports of Ministry of Health, materials presented at review meetings, and findings from supervisory visits to districts and health facilities. Our results suggest that Ethiopia has made significant strides toward strengthening LTBI management in people living with HIV and among under-five-year-old household contacts of TB patients. The use of contact investigation as entry point for LTBI management could be taken as best practice. More effort is needed to further strengthen implementation of LTBI management, and it should be supported through context-specific implementation and operational research activities.

  3. Latent tuberculosis infection among sailors and civilians aboard U.S.S. Ronald Reagan--United States, January-July 2006.

    Science.gov (United States)

    2007-01-05

    Crews aboard ships live and work in crowded, enclosed spaces. Historically, large tuberculosis (TB) outbreaks and extensive transmission of Mycobacterium tuberculosis have occurred on U.S. Navy ships. On July 13, 2006, smear- and culture-positive, cavitary, pulmonary TB was diagnosed in a sailor aboard the aircraft carrier U.S.S. Ronald Reagan; the patient, aged 32 years, had a negative human immunodeficiency virus test. The M. tuberculosis strain cultured was susceptible to all first-line TB medications. The sailor was born in the Philippines, had latent tuberculosis infection (LTBI) diagnosed in 1995 shortly after enlisting in the U.S. Navy, and completed the 6-month daily isoniazid course that was standard treatment at that time (current treatment standard is 9 months). This report describes the contact investigation conducted by the U.S. Navy and CDC and demonstrates the importance of timely diagnosis of TB, identification and treatment of new LTBI, and cooperation among local, state, and federal agencies during large contact investigations.

  4. In vitro immunomodulation of a whole blood IFN-γ release assay enhances T cell responses in subjects with latent tuberculosis infection.

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    Rajiv L Gaur

    Full Text Available Activation of innate immunity via pathogen recognition receptors (PRR modulates adaptive immune responses. PRR ligands are being exploited as vaccine adjuvants and as therapeutics, but their utility in diagnostics has not been explored. Interferon-gamma (IFN-γ release assays (IGRAs are functional T cell assays used to diagnose latent tuberculosis infection (LTBI; however, novel approaches are needed to improve their sensitivity.In vitro immunomodulation of a whole blood IGRA (QuantiFERON®-TB GOLD In-Tube with Toll-like receptor agonists poly(I:C, LPS, and imiquimod was performed on blood from subjects with LTBI and negative controls.In vitro immunomodulation significantly enhanced the response of T cells stimulated with M. tuberculosis antigens from subjects with LTBI but not from uninfected controls. Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T cells otherwise do not respond to in vitro stimulation with antigens alone. Similar to their in vivo functions, addition of poly(I:C and LPS to whole blood induced secretion of inflammatory cytokines and IFN-α and enhanced the surface expression of antigen presenting and costimulatory molecules on antigen presenting cells.In vitro immunomodulation of whole blood IGRA may be an effective strategy for enhancing the sensitivity of T cells for diagnosis of LTBI.

  5. Latent class analysis of the diagnostic characteristics of PCR and conventional bacteriological culture in diagnosing intramammary infections caused by Staphylococcus aureus in dairy cows at dry off

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    Cederlöf Sara Ellinor

    2012-11-01

    Full Text Available Abstract Background Staphylococcus aureus is one of the most common causes of intramammary infections in dairy cows at dry off. Reliable identification is important for disease management on herd level and for antimicrobial treatment of infected animals. Our objective was to evaluate the test characteristics of PathoProof ™ Mastitis PCR Assay and bacteriological culture (BC in diagnosing bovine intramammary infections caused by S. aureus at dry off at different PCR cycle threshold (Ct-value cut-offs. Methods Sterile quarter samples and non-sterile composite samples from 140 animals in seven herds were collected in connection with the dairy herd improvement (DHI milk recording. All quarter samples were analyzed using BC whereas all composite samples were analyzed with PathoProof ™ Mastitis PCR Assay. Latent class analysis was used to estimate test properties for PCR and BC in the absence of a perfect reference test. The population was divided into two geographically divided subpopulations and the Hui-Walter 2-test 2-populations model applied to estimate Se, Sp for the two tests, and prevalence for the two subpopulations. Results The Se for PCR increased with increasing Ct-value cut-off, accompanied by a small decrease in Sp. For BC the Se decreased and Sp increased with increasing Ct-value cut-off. Most optimal test estimates for the real-time PCR assay were at a Ct-value cut-off of 37; 0.93 [95% posterior probability interval (PPI 0.60-0.99] for Se and 0.95 [95% PPI 0.95-0.99] for Sp. At the same Ct-value cut-off, Se and Sp for BC were 0.83 [95% PPI 0.66-0.99] and 0.97 [95% PPI 0.91-0.99] respectively. Depending on the chosen PCR Ct-value cut-off, the prevalence in the subpopulations varied; the prevalence increased with increasing PCR Ct-value cut-offs. Conclusion Neither BC nor real-time PCR is a perfect test in detecting IMI in dairy cows at dry off. The changes in sensitivity and prevalence at different Ct-value cut-offs for both PCR and

  6. Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.

    Science.gov (United States)

    McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G

    2012-05-01

    Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

  7. Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes

    Directory of Open Access Journals (Sweden)

    Brian G. Murphy

    2012-05-01

    Full Text Available Feline immunodeficiency virus (FIV, the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

  8. Estudio multicéntrico de prevalencia de infección tuberculosa latente en los internados en prisiones españolas Multi-centre study of the prevalance of latent tuberculosis infection amongst inmates in spanish prisons

    Directory of Open Access Journals (Sweden)

    J. García-Guerrero

    2010-02-01

    Full Text Available Objetivo: Estudiar la prevalencia de infección tuberculosa latente (ITL entre los presos internados en las prisiones españolas. Material y Método: Estudio multicéntrico, observacional y transversal; muestreo por conglomerado bietápico. Se recogieron variables sociodemográficas, penitenciarias y clínico-serológicas. Se realizó análisis univariante, bivariante y multivariante mediante regresión logística con las variables que mostraron significación estadística. Se calculó la odds ratio con intervalo de confianza del 95%. Resultados: 378 pacientes. Se dispuso de intradermorreacción de Mantoux (IDRM valorable en el 90,2%. 91,2% hombres, 37,8% extranjeros con edad media de 35,9±10,3 años. Mediana de estancia en prisión: 2 años y el 28,7% había estado > 5 años en prisión. El 49,6% ingresó en prisión en 2006 o antes. El 24,5% tenía antecedentes de uso de drogas intravenosas (UDI. El 50,4% presentaba ITL que se asoció a: edad > 40 años (63,2 vs 43,8%; IC: 1,39-3,49; OR: 2,20; p=0,001; haber estado > 5 años en prisión (71,2 vs 41,3%; IC: 2,13-5,75; OR: 3,50; p 40 años (OR:1,76; IC: 1,08-2,87; p=0,024; y b estancia > 5 años en prisión (OR: 2,50; IC: 1,41-4,43; p=0,002. Conclusiones: La prevalencia de ITL en prisión es muy alta, sobre todo en los mayores de 40 años y los que están más de cinco años en prisión. Para evitar el riesgo de progresión a tuberculosis, se recomienda tratar a los infectados que lo precisen y mantener los programas de control de esta patología.Aims: To study the prevalence of latent tuberculosis infection (LTBI amongst inmates in Spanish prisons. Materials and Methods: Multi-centre, cross-sectional study; two stage sampling. Socio-demographic, prison and clinical variables were gathered. A univariate, bivariate and multivariate analysis was carried out using logistic regression with the variables that showed statistical significance. The odds ratio was calculated with a confidence interval

  9. The Effects of Age and Latent Cytomegalovirus Infection on NK-Cell Phenotype and Exercise Responsiveness in Man

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    Austin B. Bigley

    2015-01-01

    Full Text Available The redeployment of NK-cells in response to an acute bout of exercise is thought to be an integral component of the “fight-or-flight” response, preparing the body for potential injury or infection. We showed previously that CMV seropositivity impairs the redeployment of NK-cells with exercise in the young. In the current study, we examined the effect of aging on the redeployment of NK-cells with exercise in the context of CMV. We show here that CMV blunts the exercise-induced redeployment of NK-cells in both younger (23–39 yrs and older (50–64 yrs subjects with older CMVneg subjects showing the largest postexercise mobilization and 1 h postexercise egress of NK-cells. The blunted exercise response in CMVpos individuals was associated with a decreased relative redeployment of the CD158a+ and CD57+ NK-cell subsets in younger and older individuals. In addition, we show that aging is associated with a CMV-independent increase in the proportion of NK-cells expressing the terminal differentiation marker CD57, while CMV is associated with an age-dependent decrease in the proportion of NK-cells expressing the inhibitory receptors KLRG1 (in the younger group and CD158a (in the older group. Collectively, these data suggest that CMV may decrease NK-cell mediated immunosurveillance after exercise in both younger and older individuals.

  10. Rapid CRISPR/Cas9-Mediated Cloning of Full-Length Epstein-Barr Virus Genomes from Latently Infected Cells

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    Misako Yajima

    2018-04-01

    Full Text Available Herpesviruses have relatively large DNA genomes of more than 150 kb that are difficult to clone and sequence. Bacterial artificial chromosome (BAC cloning of herpesvirus genomes is a powerful technique that greatly facilitates whole viral genome sequencing as well as functional characterization of reconstituted viruses. We describe recently invented technologies for rapid BAC cloning of herpesvirus genomes using CRISPR/Cas9-mediated homology-directed repair. We focus on recent BAC cloning techniques of Epstein-Barr virus (EBV genomes and discuss the possible advantages of a CRISPR/Cas9-mediated strategy comparatively with precedent EBV-BAC cloning strategies. We also describe the design decisions of this technology as well as possible pitfalls and points to be improved in the future. The obtained EBV-BAC clones are subjected to long-read sequencing analysis to determine complete EBV genome sequence including repetitive regions. Rapid cloning and sequence determination of various EBV strains will greatly contribute to the understanding of their global geographical distribution. This technology can also be used to clone disease-associated EBV strains and test the hypothesis that they have special features that distinguish them from strains that infect asymptomatically.

  11. Fast Technology Analysis (FTA) Enables Identification of Species and Genotypes of Latent Microsporidia Infections in Healthy Native Cameroonians

    Science.gov (United States)

    Ndzi, Edward S.; Asonganyi, Tazoacha; Nkinin, Mary Bello; Xiao, Lihua; Didier, Elizabeth S.; Bowers, Lisa C.; Nkinin, Stephenson W.; Kaneshiro, Edna S.

    2015-01-01

    Several enteric microsporidia species have been detected in humans and other vertebrates and their identifications at the genotype level are currently being elucidated. As advanced methods, reagents, and disposal kits for detecting and identifying pathogens become commercially available, it is important to test them in settings other than in laboratories with “state-of-the-art” equipment and well-trained staff members. In the present study, we sought to detect microsporidia DNA preserved and extracted from FTA (fast technology analysis) cards spotted with human fecal suspensions obtained from Cameroonian volunteers living in the capital city of Yaoundé to preclude the need for employing spore-concentrating protocols. Further, we tested whether amplicon nucleotide sequencing approaches could be used on small aliquots taken from the cards to elucidate the diversity of microsporidia species and strains infecting native residents. Of 196 samples analyzed, 12 (6.1%) were positive for microsporidia DNA; Enterocytozoon bieneusi (Type IV and KIN-1), Encephalitozoon cuniculi, and Encephalitozoon intestinalis were identified. These data demonstrate the utility of the FTA cards in identifying genotypes of microsporidia DNA in human fecal samples that may be applied to field testing for prevalence studies. PMID:26303263

  12. Rapid CRISPR/Cas9-Mediated Cloning of Full-Length Epstein-Barr Virus Genomes from Latently Infected Cells.

    Science.gov (United States)

    Yajima, Misako; Ikuta, Kazufumi; Kanda, Teru

    2018-04-03

    Herpesviruses have relatively large DNA genomes of more than 150 kb that are difficult to clone and sequence. Bacterial artificial chromosome (BAC) cloning of herpesvirus genomes is a powerful technique that greatly facilitates whole viral genome sequencing as well as functional characterization of reconstituted viruses. We describe recently invented technologies for rapid BAC cloning of herpesvirus genomes using CRISPR/Cas9-mediated homology-directed repair. We focus on recent BAC cloning techniques of Epstein-Barr virus (EBV) genomes and discuss the possible advantages of a CRISPR/Cas9-mediated strategy comparatively with precedent EBV-BAC cloning strategies. We also describe the design decisions of this technology as well as possible pitfalls and points to be improved in the future. The obtained EBV-BAC clones are subjected to long-read sequencing analysis to determine complete EBV genome sequence including repetitive regions. Rapid cloning and sequence determination of various EBV strains will greatly contribute to the understanding of their global geographical distribution. This technology can also be used to clone disease-associated EBV strains and test the hypothesis that they have special features that distinguish them from strains that infect asymptomatically.

  13. Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

    Science.gov (United States)

    Cotton, Sarah; Brown, Robert E; Nugent, Elizabeth K; Robazetti, Sonia C; Berens, Pamela D; Smith, Judith A

    2018-04-01

    To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay

  14. Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

    Science.gov (United States)

    Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

    2016-02-01

    Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

  15. Effect of changes in the nutritional status on the performances of growing Creole kids during an established nematode parasite infection.

    Science.gov (United States)

    Ceï, W; Archimède, H; Arquet, R; Félicité, Y; Feuillet, D; Nepos, A; Mulciba, P; Etienne, T; Alexandre, G; Bambou, J C

    2017-04-01

    In this study, we evaluated the effect of changes in the nutritional status on the performances of growing Creole kids during an established experimental gastrointestinal nematode (GIN) infection. Eighteen 6-month-old Creole kids were distributed in two main groups infected (I) and non-infected (NI) and were placed for a period of 4 weeks on each of three diets differing in their nutritional values: (1) fresh grass (FG, 6.7 MJ/kg dry matter (DM) and 7.9% crude protein (CP)) non-supplemented, (2) FG supplemented with a commercial concentrate (CC, 12.2 MJ/kg DM and 20.6% of CP), and (3) FG supplemented with dried banana (Ban, 11.1 MJ/kg DM and 4.3% CP). The experiment was designed as a split-plot with experimental infection (I and NI) as the main plot and the diets (FG, CC, and Ban) as the subplots with three replicates. We showed a significant effect of the diet changes on the fecal egg counts. A higher dry matter intake, digestibility, and growth rate were observed with the CC diet but together with a slight but significant increase of the intensity of the GIN infection. These data suggest that the improvement of the protein nutritional status during an establish GIN infection would improve the animal performance at the expense of the mechanism involved in the control of the infection.

  16. Estimation of test characteristics of real-time PCR and bacterial culture for diagnosis of subclinical intramammary infections with Streptococcus agalactiae in Danish dairy cattle in 2012 using latent class analysis.

    Science.gov (United States)

    Mahmmod, Yasser S; Toft, Nils; Katholm, Jørgen; Grønbæk, Carsten; Klaas, Ilka C

    2013-05-01

    The misdiagnosis of intramammary infections (IMI) with Streptococcus agalactiae (S. agalactiae) could lead farmers to treat or cull animals unnecessarily. The objective of this field study was to estimate the sensitivity (Se) and specificity (Sp) of real-time PCR at different cut-offs for cycle threshold (Ct) values against bacterial culture (BC) for diagnosis of S. agalactiae IMI using latent class analysis to avoid the assumption of a perfect reference test. A total of 614 dairy cows were randomly selected from 6 herds with bulk tank PCR Ct value ≤ 39 for S. agalactiae and S. aureus. At milk recording, 2456 quarter milk samples were taken aseptically for BC and the routinely taken cow level milk samples were analyzed by PCR. Results showed that 53 cows (8.6%) were positive for S. agalactiae IMI by BC. Sensitivity of PCR at cut-offs; ≤ 39, ≤ 37, ≤ 34, and ≤ 32, was 96.2%, 91.9%, 87.2% and 73.9%, while Se of BC was 25.7%, 29.9%, 59.9% and 72.1%. Specificity of PCR at cut-offs; ≤ 39, ≤ 37, ≤ 34, and ≤ 32, was 96.8%, 96.9%, 96.7%, and 97.22%, while Sp of BC was 99.7%, 99.5%, 99.2%, and 98.9%. The estimated prevalence of S. agalactiae IMI by PCR was higher than the apparent prevalence at the tested cut-offs, indicating under estimation of S. agalactiae IMI in the examined dairy cows. In conclusion, Se of PCR is always higher than Se of BC at all tested cut-offs. The lower cut-off, the more comparable becomes Se of PCR and Se of BC. The changes in Se in both PCR and BC at different Ct-value cut-offs may indicate a change in the definition of the latent infection. The similar Se of both tests at cut-off ≤ 32 may indicate high concentrations of S. agalactiae viable cells, representing a cow truly/heavily infected with S. agalactiae and thus easier to detect with BC. At cut-off ≤ 39 the latent definition of infection may reflect a more general condition of cows being positive for S. agalactiae. Our findings indicate that PCR Ct-value cut-offs should

  17. Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: a brief report.

    Science.gov (United States)

    Tabarsi, Payam; Yousefzadeh, Amir; Najafizadeh, Katayoun; Droudinia, Atousa; Bayati, Rouzbeh; Marjani, Majid; Shafaghi, Shadi; Farokhzad, Banafsheh; Javanmard, Pedram; Velayati, Ali Akbar

    2014-11-01

    With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA). The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%). Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

  18. Latent tuberculosis infection, tuberculin skin test and vitamin D status in contacts of tuberculosis patients: a cross-sectional and case-control study

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    Arnedo-Pena Alberto

    2011-12-01

    Full Text Available Abstract Background Deficient serum vitamin D levels have been associated with incidence of tuberculosis (TB, and latent tuberculosis infection (LTBI. However, to our knowledge, no studies on vitamin D status and tuberculin skin test (TST conversion have been published to date. The aim of this study was to estimate the associations of serum 25-hydroxyvitamin D3 (25[OH]D status with LTBI prevalence and TST conversion in contacts of active TB in Castellon (Spain. Methods The study was designed in two phases: cross-sectional and case-control. From November 2009 to October 2010, contacts of 42 TB patients (36 pulmonary, and 6 extra-pulmonary were studied in order to screen for TB. LTBI and TST conversion cases were defined following TST, clinical, analytic and radiographic examinations. Serum 25(OHD levels were measured by electrochemiluminescence immunoassay (ECLIA on a COBAS® 410 ROCHE® analyzer. Logistic regression models were used in the statistical analysis. Results The study comprised 202 people with a participation rate of 60.1%. Only 20.3% of the participants had a sufficient serum 25(OHD (≥ 30 ng/ml level. In the cross-sectional phase, 50 participants had LTBI and no association between LTBI status and serum 25(OHD was found. After 2 months, 11 out of 93 negative LTBI participants, without primary prophylaxis, presented TST conversion with initial serum 25(OHD levels: a:19.4% (7/36: Conclusions The results suggest that sufficient serum 25(OHD levels protect against TST conversion.

  19. Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: A brief report

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    Payam Tabarsi

    2014-01-01

    Full Text Available With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA in reaction to early secreted antigenic target 6 (ESAT-6, culture filtrate protein 10 (CFP-10, and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA. The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9% turned out to be positive, negative for 24 donors (63.1%, and indeterminate for 11 cases (28.9%. Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

  20. Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

    Science.gov (United States)

    Stockbridge, Erica L; Miller, Thaddeus L; Carlson, Erin K; Ho, Christine

    Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector. To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims. Medical and pharmacy claims data representing insurance-paid services rendered and prescriptions filled between January 2011 and March 2015 were analyzed. Four million commercially insured individuals 0 to 64 years of age. Six-month and 9-month treatment completion rates for isoniazid LTBI regimens. There was an annual isoniazid LTBI treatment initiation rate of 12.5/100 000 insured persons. Of 1074 unique courses of treatment with isoniazid for which treatment completion could be assessed, almost half (46.3%; confidence interval, 43.3-49.3) completed 6 or more months of therapy. Of those, approximately half (48.9%; confidence interval, 44.5-53.3) completed 9 months or more. Claims data can be used to identify and evaluate LTBI treatment with isoniazid occurring in the commercial sector. Completion rates were in the range of those found in public health settings. These findings suggest that the commercial sector may be a valuable adjunct to more traditional venues for tuberculosis prevention. In addition, these newly developed claims-based methods offer a means to gain important insights and open new avenues to monitor, evaluate, and coordinate tuberculosis prevention.

  1. Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test.

    Science.gov (United States)

    Bukhary, Zakeya A; Amer, Soliman M; Emara, Magdy M; Abdalla, Mohammad E; Ali, Sahar A

    2018-01-01

    Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. Cross-sectional prospective. Multiple non-tertiary care hospitals. HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods. The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. 520 subjects. Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. A second step TST was not feasible within 2-3 weeks. None.

  2. Frequent Detection of Anti-Tubercular-Glycolipid-IgG and -IgA Antibodies in Healthcare Workers with Latent Tuberculosis Infection in the Philippines

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    Umme Ruman Siddiqi

    2012-01-01

    Full Text Available Anti-tubercular-glycolipid-IgG (TBGL-IgG and -IgA (TBGL-IgA antibodies, and the QuantiFERON-TB Gold test (QFT were compared in healthcare workers (HCWs, n=31 and asymptomatic human immunodeficiency virus-carriers (HIV-AC, n=56 in Manila. In HCWs, 48%, 51%, and 19% were positive in QFT, TBGL-IgG, and -IgA, respectively. The TBGL-IgG positivity was significantly higher (P=0.02 in QFT-positive than QFT-negative HCWs. Both TBGL-IgG- and -IgA-positive cases were only found in QFT-positive HCWs (27%. The plasma IFN-γ levels positively correlated with TBGL-IgA titers (r=0.74, P=0.005, but not TBGL-IgG titers in this group, indicating that mucosal immunity is involved in LTBI in immunocompetent individuals. The QFT positivity in HIV-AC was 31% in those with CD4+ cell counts >350/μL and 12.5% in low CD4 group (<350/μL. 59 % and 29% were positive for TBGL-IgG and -IgA, respectively, in HIV-AC, but no association was found between QFT and TBGL assays. TBGL-IgG-positive rates in QFT-positive and QFT-negative HIV-AC were 61% and 58%, and those of TBGL-IgA were 23% and 30%, respectively. The titers of TBGL-IgA were associated with serum IgA (P=0.02 in HIV-AC. Elevations of TBGL-IgG and -IgA were related to latent tuberculosis infection in HCWs, but careful interpretation is necessary in HIV-AC.

  3. Estimation of test characteristics of real-time PCR and bacterial culture for diagnosis of subclinical intramammary infections with Streptococcus agalactiae in Danish dairy cattle in 2012 using latent class analysis

    DEFF Research Database (Denmark)

    Mahmmod, Yasser; Toft, Nils; Katholm, Jørgen

    2013-01-01

    threshold (Ct) values against bacterial culture (BC) for diagnosis of S. agalactiae IMI using latent class analysis to avoid the assumption of a perfect reference test. A total of 614 dairy cows were randomly selected from 6 herds with bulk tank PCR Ct value ≤ 39 for S. agalactiae and S. aureus. At milk...... cut-offs, indicating under estimation of S. agalactiae IMI in the examined dairy cows. In conclusion, Se of PCR is always higher than Se of BC at all tested cut-offs. The lower cut-off, the more comparable becomes Se of PCR and Se of BC. The changes in Se in both PCR and BC at different Ct-value cut...... definition of infection may reflect a more general condition of cows being positive for S. agalactiae. Our findings indicate that PCR Ct-value cut-offs should be chosen according to the underlying latent infection definition of interest. Latent class analysis proposes a useful alternative to classic test...

  4. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2015-07-01

    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  5. Establishment of fruit bat cells (Rousettus aegyptiacus as a model system for the investigation of filoviral infection.

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    Verena Krähling

    Full Text Available BACKGROUND: The fruit bat species Rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus Marburg virus. To establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, R06E, derived from the species Rousettus aegyptiacus. METHODOLOGY/PRINCIPAL FINDINGS: Upon infection with Ebola or Marburg viruses, R06E cells produced viral titers comparable to VeroE6 cells, as shown by TCID(50 analysis. Electron microscopic analysis of infected cells revealed morphological signs of filovirus infection as described for human- and monkey-derived cell lines. Using R06E cells, we detected an unusually high amount of intracellular viral proteins, which correlated with the accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We established protocols to produce Marburg infectious virus-like particles from R06E cells, which were then used to infect naïve target cells to investigate primary transcription. This was not possible with other cell lines previously tested. Moreover, we established protocols to reliably rescue recombinant Marburg viruses from R06E cells. CONCLUSION/SIGNIFICANCE: These data indicated that R06E cells are highly suitable to investigate the biology of filoviruses in cells derived from their presumed reservoir.

  6. A potent human neutralizing antibody Fc-dependently reduces established HBV infections.

    Science.gov (United States)

    Li, Dan; He, Wenhui; Liu, Ximing; Zheng, Sanduo; Qi, Yonghe; Li, Huiyu; Mao, Fengfeng; Liu, Juan; Sun, Yinyan; Pan, Lijing; Du, Kaixin; Ye, Keqiong; Li, Wenhui; Sui, Jianhua

    2017-09-26

    Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.

  7. Establishment of infection models in zebrafish larvae (Danio rerio to study the pathogenesis of Aeromonas hydrophila.

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    Paolo Roberto Saraceni

    2016-08-01

    Full Text Available Aeromonas hydrophila is a Gram-negative opportunistic pathogen of fish and terrestrial animals. In humans, A. hydrophila mainly causes gastroenteritis, septicaemia and tissue infections. The mechanisms of infection, the main virulence factors and the host immune response triggered by A. hydrophila have been studied in detail using murine models and adult fish. However, the great limitation of studying adult animals is that the animal must be sacrificed and its tissues/organs extracted, which prevents the study of the infectious processes in the whole living animal.Zebrafish larvae are being used for the analysis of several infectious diseases, but their use for studying the pathogenesis of A. hydrophila has never been explored. The great advantage of zebrafish larvae is their transparency during the first week after fertilization, which allows detailed descriptions of the infectious processes using in vivo imaging techniques such as differential interferential contrast (DIC and fluorescence microscopy. Moreover, the availability of fluorescent pathogens and transgenic reporter zebrafish lines expressing fluorescent immune cells, immune marker genes or cytokines/chemokines allows the host-pathogen interactions to be characterized.The present study explores the suitability of zebrafish larvae to study the pathogenesis of A. hydrophila and the interaction mechanisms between the bacterium and the innate immune responses through an infection model using different routes for infection. We used an early-embryo infection model at 3 days post-fertilization (dpf through the microinjection of A. hydrophila into the duct of Cuvier, caudal vein, notochord or muscle and two bath infection models using 4 dpf healthy and injured larvae. The latter resembled the natural conditions under which A. hydrophila produces infectious diseases in animals. We compared the cellular processes after infection in each anatomical site by confocal fluorescence imaging and

  8. Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

    Science.gov (United States)

    Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

    2014-01-01

    To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical

  9. The Association between active and passive smoking and latent tuberculosis infection in adults and children in the united states: results from NHANES.

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    Ryan P Lindsay

    Full Text Available Few studies assessing the relationship between active and passive smoking and tuberculosis have used biomarkers to measure smoke exposure. We sought to determine the association between active and passive smoking and LTBI in a representative sample of US adults and children.We used the 1999-2000 US National Health and Nutrition Examination Survey (NHANES dataset with tuberculin skin test (TST data to assess the association between cotinine-confirmed smoke exposure and latent tuberculosis infection (LTBI among adults ages ≥20 years (n = 3598 and children 3-19 years (n = 2943 and estimate the prevalence of smoke exposure among those with LTBI. Weighted multivariate logistic regression was used to measure the associations between active and passive smoking and LTBI.LTBI prevalence in 1999-2000 among cotinine-confirmed active, passive, and non-smoking adults and children was 6.0%, 5.2%, 3.3% and 0.3%, 1.0%, 1.5%, respectively. This corresponds to approximately 3,556,000 active and 3,379,000 passive smoking adults with LTBI in the US civilian non-institutionalized population in 1999-2000. Controlling for age, gender, socioeconomic status, race, birthplace (US vs. foreign-born, household size, and having ever lived with someone with TB, adult active smokers were significantly more likely to have LTBI than non-smoking adults (AOR = 2.31 95% CI 1.17-4.55. Adult passive smokers also had a greater odds of LTBI compared with non-smokers, but this association did not achieve statistical significance (AOR = 2.00 95% CI 0.87-4.60. Neither active or passive smoking was associated with LTBI among children. Among only the foreign-born adults, both active (AOR = 2.56 (95% CI 1.20-5.45 and passive smoking (AOR = 2.27 95% CI 1.09-4.72 were significantly associated with LTBI.Active adult smokers and both foreign-born active and passive smokers in the United States are at elevated risk for LTBI. Targeted smoking prevention and cessation

  10. The assessment of cytokines in Quantiferon supernatants for the diagnosis of latent TB infection in a tribal population of Melghat, India.

    Science.gov (United States)

    Bapat, Prachi R; Husain, Aliabbas A; Daginawala, Hatim F; Agrawal, Neha P; Panchbhai, Milind S; Satav, Ashish R; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    The tuberculin skin test (TST) and interferon-gamma release assays (IGRA), namely, the QuantiFERON-TB Gold test (QFT), remain the standard immunological diagnostic tools for latent tuberculosis (TB) infection (LTBI). However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ) as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i) QFT+/TST+ (n = 26), (ii) QFT+/TST- (n = 12), (iii) QFT-/TST- (n = 35) and (iv) QFT-/TST+ (n = 1) groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R) was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT-/TST- group. Correlation analysis identified a positive correlation between IL-6 and the QFT response (r = 0.6723, P < 0.0001), while a negative correlation was seen between QFT and IL-10 expression (r = -0.3271, P = 0.0044). Similarly, IL-6 was positively correlated with TST levels (r = 0.6631, P <0 .0001), and conversely, a negative correlation was found between TST and IL-10 expression (r = -0.5698, P < 0.0001). The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection

  11. The assessment of cytokines in Quantiferon supernatants for the diagnosis of latent TB infection in a tribal population of Melghat, India

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    Prachi R. Bapat

    2015-07-01

    Full Text Available Summary: The tuberculin skin test (TST and interferon-gamma release assays (IGRA, namely, the QuantiFERON-TB Gold test (QFT, remain the standard immunological diagnostic tools for latent tuberculosis (TB infection (LTBI. However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i QFT+/TST+ (n = 26, (ii QFT+/TST− (n = 12, (iii QFT−/TST− (n = 35 and (iv QFT−/TST+ (n = 1 groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT−/TST− group. Correlation analysis identified a positive correlation between IL-6 and the QFT response (r = 0.6723, P < 0.0001, while a negative correlation was seen between QFT and IL-10 expression (r = −0.3271, P = 0.0044. Similarly, IL-6 was positively correlated with TST levels (r = 0.6631, P < 0.0001, and conversely, a negative correlation was found between TST and IL-10 expression (r = −0.5698, P < 0.0001. The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and

  12. Comparison of interferon-γ release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers.

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    Fernanda Mattos de Souza

    Full Text Available An interferon-γ release assay, QuantiFERON-TB (QFT test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI. Here, we compared the performance of QFT with tuberculin skin test (TST measured at two different cut-off points among primary health care work (HCW in Brazil.A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5 mm and ≥10 mm as cut-off points.We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k = 0.31, and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k = 0.22. We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group, risk factors for discordance in the TST+/QFT- group with TST cut-off of ≥5 mm included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years [OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of ≥10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly associated with the TST+/QFT- group. No statistically significant associations were found among the TST-/QFT+ discordant group with either TST cut-off value.Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed.

  13. Comparison of interferon-γ release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers.

    Science.gov (United States)

    de Souza, Fernanda Mattos; do Prado, Thiago Nascimento; Pinheiro, Jair dos Santos; Peres, Renata Lyrio; Lacerda, Thamy Carvalho; Loureiro, Rafaela Borge; Carvalho, Jose Américo; Fregona, Geisa; Dias, Elias Santos; Cosme, Lorrayne Beliqui; Rodrigues, Rodrigo Ribeiro; Riley, Lee Wood; Maciel, Ethel Leonor Noia

    2014-01-01

    An interferon-γ release assay, QuantiFERON-TB (QFT) test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care work (HCW) in Brazil. A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5 mm and ≥10 mm as cut-off points. We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k = 0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group, risk factors for discordance in the TST+/QFT- group with TST cut-off of ≥5 mm included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years [OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of ≥10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly associated with the TST+/QFT- group. No statistically significant associations were found among the TST-/QFT+ discordant group with either TST cut-off value. Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed.

  14. Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions.

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    Aruna Amarasinghe

    Full Text Available Infectious bronchitis virus (IBV causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41 and Connecticut A5968 (Conn A5968 strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.

  15. Lymphocytes and macrophages are infected by Theileria equi, but T cells and B cells are not required to establish infection in vivo.

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    Joshua D Ramsay

    Full Text Available Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata, the intraleukocyte stage (schizont of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID, which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis

  16. 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...

  17. Latent class analysis of the diagnostic characteristics of PCR and conventional bacteriological culture in diagnosing intramammary infections caused by Staphylococcus aureus in dairy cows at dry off

    DEFF Research Database (Denmark)

    Cederlöf, Sara Ellinor; Toft, Nils; Aalbæk, Bent

    2012-01-01

    characteristics of PathoProof TM Mastitis PCR Assay and bacteriological culture (BC) in diagnosing bovine intramammary infections caused by S. aureus at dry off at different PCR cycle threshold (Ct)-value cut-offs. METHODS: Sterile quarter samples and non-sterile composite samples from 140 animals in seven herds...... were collected in connection with the dairy herd improvement (DHI) milk recording. All quarter samples were analyzed using BC whereas all composite samples were analyzed with PathoProof TM Mastitis PCR Assay. Latent class analysis was used to estimate test properties for PCR and BC in the absence...

  18. Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection.

    Science.gov (United States)

    Uppu, Divakara S S M; Samaddar, Sandip; Ghosh, Chandradhish; Paramanandham, Krishnamoorthy; Shome, Bibek R; Haldar, Jayanta

    2016-01-01

    Bacterial biofilms represent the root-cause of chronic or persistent infections in humans. Gram-negative bacterial infections due to nosocomial and opportunistic pathogens such as Acinetobacter baumannii are more difficult to treat because of their inherent and rapidly acquiring resistance to antibiotics. Due to biofilm formation, A. baumannii has been noted for its apparent ability to survive on artificial surfaces for an extended period of time, therefore allowing it to persist in the hospital environment. Here we report, maleic anhydride based novel cationic polymers appended with amide side chains that disrupt surface established multi-drug resistant A. baumannii biofilms. More importantly, these polymers significantly (p polymers also show potent antibacterial efficacy against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococci (VRE) and multi-drug resistant clinical isolates of A. baumannii with minimal toxicity to mammalian cells. We observe that optimal hydrophobicity dependent on the side chain chemical structure of these polymers dictate the selective toxicity to bacteria. Polymers interact with the bacterial cell membranes by causing membrane depolarization, permeabilization and energy depletion. Bacteria develop rapid resistance to erythromycin and colistin whereas no detectable development of resistance occurs against these polymers even after several passages. These results suggest the potential use of these polymeric biomaterials in disinfecting biomedical device surfaces after the infection has become established and also for the topical treatment of chronic bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

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    Senthilnathan Palaniyandi

    Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

  20. Intrauterine inoculation of minipigs with Chlamydia trachomatis during diestrus establishes a longer lasting infection compared to vaginal inoculation during estrus.

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Secher, Jan O; Goericke-Pesch, Sandra; Hansen, Mette S; Zakariassen, Hannah; Olsen, Anja W; Andersen, Peter; Jungersen, Gregers; Agerholm, Jørgen S

    2017-06-01

    Advanced animal models, such as minipigs, are needed for the development of a globally requested human Chlamydia vaccine. Previous studies have shown that vaginal inoculation of sexually mature Göttingen minipigs with Chlamydia trachomatis resulted in an infection lasting only 3-5 days. The aim of this study was to evaluate the effect of targeting the upper porcine genital tract by transcervical and transabdominal intrauterine inoculation, compared to previously performed vaginal inoculation. Furthermore, we investigated the effect of the hormonal cycle, estrus vs. diestrus, on the establishment of a C. trachomatis infection in the minipig. Targeting the upper genital tract (transcervical inoculation) resulted in a longer lasting infection (at least 7 days) compared to vaginal inoculation (3-5 days). When comparing intrauterine inoculation during estrus and diestrus, inoculation during diestrus resulted in a longer lasting infection (at least 10 days) compared to estrus (3-5 days). Furthermore, we found a significant C. trachomatis specific IFN-γ response in pigs inoculated during estrus correlating with the accelerated clearance of infection in these pigs. These findings suggest that for implementation of an optimal model of C. trachomatis in minipigs, inoculation should bypass the cervix and preferable be performed during diestrus. Copyright © 2017 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

  1. β-Hemolysin/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection.

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    Ritwij Kulkarni

    Full Text Available Group B Streptococcus (GBS; Streptococcus agalactiae is a major human pathogen that disproportionately affects neonates and women in the peripartum period and is an emerging cause of infection in older adults. The primary toxin of GBS, β-hemolysin/cytolysin (βH/C, has a well-defined role in the pathogenesis of invasive disease, but its role in urinary tract infection (UTI is unknown. Using both in vitro and in vivo models, we analyzed the importance of βH/C in GBS uropathogenesis. There were no significant differences in bacterial density from the bladders or kidneys from mice infected with wild-type or isogenic βH/C-deficient GBS, and competitive indices from co-infection experiments were near 1. Thus, βH/C is dispensable for the establishment of GBS-UTI. However, βH/C-sufficient GBS induced a more robust proinflammatory cytokine response in cultured bladder epithelial cells and in the urinary tracts of infected mice. Given the near ubiquity of βH/C-expressing strains in epidemiologic studies and the importance of local inflammation in dictating outcomes and sequelae of UTI, we hypothesize that βH/C-driven inflammatory signaling may be important in the clinical course of GBS-UTI.

  2. Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection.

    Science.gov (United States)

    Veras, Patrícia Sampaio Tavares; Bezerra de Menezes, Juliana Perrone

    2016-08-19

    Leishmania is a protozoan parasite that causes a wide range of different clinical manifestations in mammalian hosts. It is a major public health risk on different continents and represents one of the most important neglected diseases. Due to the high toxicity of the drugs currently used, and in the light of increasing drug resistance, there is a critical need to develop new drugs and vaccines to control Leishmania infection. Over the past few years, proteomics has become an important tool to understand the underlying biology of Leishmania parasites and host interaction. The large-scale study of proteins, both in parasites and within the host in response to infection, can accelerate the discovery of new therapeutic targets. By studying the proteomes of host cells and tissues infected with Leishmania, as well as changes in protein profiles among promastigotes and amastigotes, scientists hope to better understand the biology involved in the parasite survival and the host-parasite interaction. This review demonstrates the feasibility of proteomics as an approach to identify new proteins involved in Leishmania differentiation and intracellular survival.

  3. 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

  4. Tissue-specific control of latent CMV reactivation by regulatory T cells.

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    Maha Almanan

    2017-08-01

    Full Text Available Cytomegalovirus (CMV causes a persistent, lifelong infection. CMV persists in a latent state and undergoes intermittent subclinical viral reactivation that is quelled by ongoing T cell responses. While T cells are critical to maintain control of infection, the immunological factors that promote CMV persistence remain unclear. Here, we investigated the role of regulatory T cells (Treg in a mouse model of latent CMV infection using Foxp3-diphtheria toxin receptor (Foxp3-DTR mice. Eight months after infection, MCMV had established latency in the spleen, salivary gland, lung, and pancreas, which was accompanied by an increased frequency of Treg. Administration of diphtheria toxin (DT after establishment of latency efficiently depleted Treg and drove a significant increase in the numbers of functional MCMV-specific CD4+ and CD8+ T cells. Strikingly, Treg depletion decreased the number of animals with reactivatable latent MCMV in the spleen. Unexpectedly, in the same animals, ablation of Treg drove a significant increase in viral reactivation in the salivary gland that was accompanied with augmented local IL-10 production by Foxp3-CD4+T cells. Further, neutralization of IL-10 after Treg depletion significantly decreased viral load in the salivary gland. Combined, these data show that Treg have divergent control of MCMV infection depending upon the tissue. In the spleen, Treg antagonize CD8+ effector function and promote viral persistence while in the salivary gland Treg prevent IL-10 production and limit viral reactivation and replication. These data provide new insights into the organ-specific roles of Treg in controlling the reactivation of latent MCMV infection.

  5. Relevance of various animal models of human infections to establish therapeutic equivalence of a generic product of piperacillin/tazobactam.

    Science.gov (United States)

    Agudelo, Maria; Rodriguez, Carlos A; Zuluaga, Andres F; Vesga, Omar

    2015-02-01

    After demonstrating with diverse intravenous antibacterials that pharmaceutical equivalence (PE) does not predict therapeutic equivalence, we tested a single generic product of piperacillin/tazobactam (TZP) in terms of PE, pharmacokinetics and in vitro/vivo pharmacodynamics against several pathogens in neutropenic mouse thigh, lung and brain infection models. A generic product was compared head-to-head against the innovator. PE was evaluated by microbiological assay. Single-dose serum pharmacokinetics were determined in infected mice, and the MIC/MBC were determined by broth microdilution. In vivo experiments were done in a blind fashion. Reproducibility was tested on different days using different infecting organisms and animal models. Neutropenic MPF mice were infected in the thighs with Staphylococcus aureus GRP-0057 or Pseudomonas aeruginosa PA01 and in the lungs or brain with Klebsiella pneumoniae ATCC 10031. Treatment started 2h (thigh and brain) or 14 h (lung) after infection and was administered every 3h over 24h (thigh and lung) or 48 h (brain). Both products exhibited the same MIC/MBC against each strain, yielded overlaid curves in the microbiological assay (P>0.21) and were bioequivalent (IC90 83-117% for AUC test/reference ratio). In vivo, the generic product and innovator were again undistinguishable in all models and against the different bacterial pathogens involved. The relevance of these neutropenic murine models of infection was established by demonstrating their accuracy to predict the biological response following simultaneous treatment with a generic product or the innovator of TZP. Therapeutic equivalence of the generic product was proved in every model and against different pathogens. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  6. Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barr virus-infected natural killer cell line established from a patient with hypersensitivity to mosquito bites.

    Science.gov (United States)

    Suzuki, Daisuke; Tsuji, Kazuhide; Yamamoto, Takenobu; Fujii, Kazuyasu; Iwatsuki, Keiji

    2010-10-01

    Cumulative evidence supports that Epstein-Barr virus (EBV)-infected natural killer (NK) cells induce severe systemic and cutaneous inflammation in patients with hypersensitivity to mosquito bites (HMB). In order to understand the pathogenesis of HMB, we established an EBV-infected cell line and characterized the cytological profiles. A novel EBV-infected NK-cell line, designated NKED, was established from a patient with HMB and used for the present study along with two other NK-cell lines, KAI3 and KHYG-1. NKED expressed the latency II-related transcripts. NKED cells were positive for CD2 and CD161 antigens, and negative for CD3, CD16, CD34, CD56, and T-cell receptor α/β and γ/δ antigens. Although NKED cells contained several cytotoxic molecules, the cells had an extremely poor cytotoxic activity. The majority of NKED cells were negative for perforin, major histocompatibility complex class I-restricted NK-cell receptors, CD94 and KIR2D, and an activating receptor, NKG2D. NKED cells, however, secreted higher levels of tumor necrosis factor-α. Stimulation with phorbol 12-myristate 13-acetate or tumor necrosis factor-α induced expression of BZLF1 messenger RNA in the NKED and KAI3 cells, indicating the transition from the latent- to the lytic-cycle infection. These data suggested that NKED cells revealed a very low cytotoxic effect probably because of the low expression levels of perforin, but had the ability to release proinflammatory cytokines. NKED cells did not reflect the characteristics of HMB, as they were different from pathogenic NK cells proliferating in the HMB patient, but the difference indicated that pathogenic NK cells could change their character in the presence of interleukin-2. Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  7. Infection Dynamics Vary between Symbiodinium Types and Cell Surface Treatments during Establishment of Endosymbiosis with Coral Larvae

    Directory of Open Access Journals (Sweden)

    Bette Lynn Willis

    2011-07-01

    Full Text Available Symbioses between microbes and higher organisms underpin high diversity in many ecosystems, including coral reefs, however mechanisms underlying the early establishment of symbioses remain unclear. Here we examine the roles of Symbiodinium type and cell surface recognition in the establishment of algal endosymbiosis in the reef-building coral, Acropora tenuis. We found 20–70% higher infection success (proportion of larvae infected and five-fold higher Symbiodinium abundance in larvae exposed to ITS-1 type C1 compared to ITS-1 type D in the first 96 h following exposure. The highest abundance of Symbiodinium within larvae occurred when C1-type cells were treated with enzymes that modified the 40–100 kD glycome, including glycoproteins and long chain starch residues. Our finding of declining densities of Symbiodinium C1 through time in the presence of intact cell surface molecules supports a role for cell surface recognition molecules in controlling post-phagocytosis processes, leading to rejection of some Symbiodinium types in early ontogeny. Reductions in the densities of unmodified C1 symbionts after 96 h, in contrast to increases in D symbionts may suggest the early initiation of a winnowing process contributing to the establishment of Symbiodinium D as the dominant type in one-month old juveniles of A. tenuis.

  8. Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection.

    Science.gov (United States)

    Niikura, Takahiro; Lee, Sang Yang; Iwakura, Takashi; Sakai, Yoshitada; Kuroda, Ryosuke; Kurosaka, Masahiro

    2016-07-01

    The treatment of established orthopaedic infection is challenging. While the main focus of treatment is wide surgical debridement, systemic and local antibiotic administration are important adjuvant therapies. Several reports have described the clinical use of antibiotic-impregnated calcium phosphate cement (CPC) to provide local antibiotic therapy for bone infections. However, these were all individual case reports, and no case series have been reported. We report a case series treated by a single surgeon using antibiotic-impregnated CPC as part of a comprehensive treatment plan in patients with established orthopaedic infection. We enrolled 13 consecutive patients with osteomyelitis (n = 6) or infected non-union (n = 7). Implantation of antibiotic-impregnated CPC was performed to provide local antibiotic therapy as part of a comprehensive treatment plan that also included wide surgical debridement, systemic antibiotic therapy, and subsequent second-stage reconstruction surgery. We investigated the rate of successful infection eradication and systemic/local complications. The concentration of antibiotics in the surgical drainage fluids, blood, and recovered CPC (via elution into a phosphate-buffered saline bath) were measured. The mean follow-up period after surgery was 50.4 (range, 27-73) months. There were no cases of infection recurrence during follow-up. No systemic toxicity or local complications from the implantation of antibiotic-impregnated CPC were observed. The vancomycin concentration in the fluid from surgical drainage (n = 6) was 527.1 ± 363.9 μg/mL on postoperative day 1 and 224.5 ± 198.4 μg/mL on postoperative day 2. In patients who did not receive systemic vancomycin therapy (n = 3), the maximum serum vancomycin level was antibiotic-impregnated CPC is an option to provide local antibiotic therapy as part of a comprehensive treatment plan. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights

  9. The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

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    Thomas Günther

    Full Text Available Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent infection with Kaposi Sarcoma-associated herpesvirus (KSHV, the etiologic agent of Kaposi Sarcoma and primary effusion lymphoma (PEL. By use of high resolution tiling microarrays in conjunction with immunoprecipitation of methylated DNA (MeDIP or modified histones (chromatin IP, ChIP, our study revealed highly distinct landscapes of epigenetic modifications associated with latent KSHV infection in several tumor-derived cell lines as well as de novo infected endothelial cells. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolve slowly and thus are unlikely to control early latency. In contrast, we observed that latency-specific histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, as H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks. Our findings suggest that the modification patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced.

  10. Establishment of gastro-intestinal helminth infections in free-range chickens: a longitudinal on farm study.

    Science.gov (United States)

    Wongrak, Kalyakorn; Daş, Gürbüz; Moors, Eva; Sohnrey, Birgit; Gauly, Matthias

    2014-01-01

    The objective of this study was to monitor establishment and development of gastro-intestinal helminth infections in chickens over two production years (PY) on a free-range farm in Lower Saxony, Germany. The data were collected between July 2010 and June 2011 (PY1) and July 2011 and January 2013 (PY2), respectively. During PY1, Lohmann Brown classic (LB classic, N = 450) was tested, while in PY2 two different genotypes (230 LB classic, 230 LB plus) were used. The hens were kept in two mobile stalls that were moved to a new position at regular intervals. In both PY1 and PY2, 20 individual faecal samples per stall were randomly collected at monthly intervals in order to calculate the number of internal parasite eggs per gram of faeces (EPG). At the end of the laying periods, approximately 10% (N = 42) or more than 50% (N = 265) of hens were subjected to post-mortem parasitological examinations in PY1 and PY2, respectively. No parasite eggs were found in the faecal samples during PY1, whereas almost all of the hens (97.6%) were infected with Heterakis gallinarum (36 worms/hen) at the end of the period. In PY2, nematode eggs in faeces were found from the third month onwards at a low level, increasing considerably towards the final three months. There was no significant difference between the two genotypes of brown hens neither for EPG (P = 0.456) or for overall prevalence (P = 0.177). Mortality rate ranged from 18.3 to 27.4% but did not differ significantly between genotypes or production years. Average worm burden was 207 worms/hen in PY2. The most prevalent species were H. gallinarum (98.5%) followed by Ascaridia galli (96.2%) and Capillaria spp. (86.1%). Furthermore, three Capillaria species, C. obsignata, C. bursata and C. caudinflata were differentiated. In conclusion chickens kept on free-range farms are exposed to high risks of nematode infections and have high mortality rates with no obvious link to parasite infections. Once the farm environment is contaminated

  11. Hook, Line and Infection: A Guide to Culturing Parasites, Establishing Infections and Assessing Immune Responses in the Three-Spined Stickleback.

    Science.gov (United States)

    Stewart, Alexander; Jackson, Joseph; Barber, Iain; Eizaguirre, Christophe; Paterson, Rachel; van West, Pieter; Williams, Chris; Cable, Joanne

    2017-01-01

    The three-spined stickleback (Gasterosteus aculeatus) is a model organism with an extremely well-characterized ecology, evolutionary history, behavioural repertoire and parasitology that is coupled with published genomic data. These small temperate zone fish therefore provide an ideal experimental system to study common diseases of coldwater fish, including those of aquacultural importance. However, detailed information on the culture of stickleback parasites, the establishment and maintenance of infections and the quantification of host responses is scattered between primary and grey literature resources, some of which is not readily accessible. Our aim is to lay out a framework of techniques based on our experience to inform new and established laboratories about culture techniques and recent advances in the field. Here, essential knowledge on the biology, capture and laboratory maintenance of sticklebacks, and their commonly studied parasites is drawn together, highlighting recent advances in our understanding of the associated immune responses. In compiling this guide on the maintenance of sticklebacks and a range of common, taxonomically diverse parasites in the laboratory, we aim to engage a broader interdisciplinary community to consider this highly tractable model when addressing pressing questions in evolution, infection and aquaculture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Stimulation of HIV-1-specific cytolytic T-lymphocytes facilitates elimination of latent viral reservoir after virus reactivation

    Science.gov (United States)

    Shan, Liang; Deng, Kai; Shroff, Neeta S.; Durand, Christine; Rabi, S. Alireza.; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B.; Blankson, Joel N.; Siliciano, Robert F.

    2012-01-01

    Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia. Life-long treatment is therefore required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T-cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4+ T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T-lymphocytes (CTL) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials. PMID:22406268

  13. Latent palmprint matching.

    Science.gov (United States)

    Jain, Anil K; Feng, Jianjiang

    2009-06-01

    The evidential value of palmprints in forensic applications is clear as about 30 percent of the latents recovered from crime scenes are from palms. While biometric systems for palmprint-based personal authentication in access control type of applications have been developed, they mostly deal with low-resolution (about 100 ppi) palmprints and only perform full-to-full palmprint matching. We propose a latent-to-full palmprint matching system that is needed in forensic applications. Our system deals with palmprints captured at 500 ppi (the current standard in forensic applications) or higher resolution and uses minutiae as features to be compatible with the methodology used by latent experts. Latent palmprint matching is a challenging problem because latent prints lifted at crime scenes are of poor image quality, cover only a small area of the palm, and have a complex background. Other difficulties include a large number of minutiae in full prints (about 10 times as many as fingerprints), and the presence of many creases in latents and full prints. A robust algorithm to reliably estimate the local ridge direction and frequency in palmprints is developed. This facilitates the extraction of ridge and minutiae features even in poor quality palmprints. A fixed-length minutia descriptor, MinutiaCode, is utilized to capture distinctive information around each minutia and an alignment-based minutiae matching algorithm is used to match two palmprints. Two sets of partial palmprints (150 live-scan partial palmprints and 100 latent palmprints) are matched to a background database of 10,200 full palmprints to test the proposed system. Despite the inherent difficulty of latent-to-full palmprint matching, rank-1 recognition rates of 78.7 and 69 percent, respectively, were achieved in searching live-scan partial palmprints and latent palmprints against the background database.

  14. Epstein-Barr virus infection and nasopharyngeal carcinoma.

    Science.gov (United States)

    Tsao, Sai Wah; Tsang, Chi Man; Lo, Kwok Wai

    2017-10-19

    Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  15. Pre-employment screening of latent tuberculosis infection among healthcare workers using tuberculin skin test and QuantiFERON-TB Gold test at a tertiary care hospital in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Mohamed El-Helaly

    2014-11-01

    Full Text Available Summary: Objective: To assess the agreement between the tuberculin skin test (TST and the QuantiFERON-TB Gold test (QFT-G as pre-employment screening tests for latent tuberculosis infection (LTBI among healthcare workers. Methods: A retrospective cross-sectional study was conducted among 1412 healthcare workers who were screened for LTBI during the period from August 2009 to May 2011 at a tertiary-care hospital in the Kingdom of Saudi Arabia (KSA. The studied population was screened for LTBI using both TST and QFT-G simultaneously. The agreement between both tests was quantified using the Kappa coefficient (κ. Results: Comparing the results of QFT-G with TST, the tests had a significant overall agreement of 73.7% (1040/1412; κ = 0.33; p < 0.01. Negative concordance comprised 60.1% of the results, and positive concordance comprised 13.5%. However, positive TST but negative QFT comprised 16.3% of the results, and negative TST but positive QFT-G comprised 10.1%. Concordance was significantly associated with young age, female gender, Saudi-born nationals, and early career but not job type (clinical versus non-clinical nor status of Bacillus Calmette–Guerin (BCG vaccination. Conclusions: This study demonstrated 73.7% overall agreement between TST and QFT-G results among healthcare workers during pre-employment screening for LTBI. The results need to be confirmed in future studies before recommending QFT-G as a pre-employment screening test for LTBI. Keywords: Latent tuberculosis infection, Healthcare workers, Tuberculin skin test, QuantiFERON-TB Gold test

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Latent classification models

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre

    2005-01-01

    parametric family ofdistributions.  In this paper we propose a new set of models forclassification in continuous domains, termed latent classificationmodels. The latent classification model can roughly be seen ascombining the \\NB model with a mixture of factor analyzers,thereby relaxing the assumptions...... classification model, and wedemonstrate empirically that the accuracy of the proposed model issignificantly higher than the accuracy of other probabilisticclassifiers....

  18. Revisiting the natural history of tuberculosis. The inclusion of constant reinfection, host tolerance, and damage-response frameworks leads to a better understanding of latent infection and its evolution towards active disease.

    Science.gov (United States)

    Cardona, Pere-Joan

    2010-02-01

    Once Mycobacterium tuberculosis infects a person it can persist for a long time in a process called latent tuberculosis infection (LTBI). LTBI has traditionally been considered to involve the bacilli remaining in a non-replicating state (dormant) in old lesions but still retaining their ability to induce reactivation and cause active tuberculosis (TB) once a disruption of the immune response takes place. The present review aims to challenge these concepts by including recent experimental data supporting LTBI as a constant endogenous reinfection process as well as the recently introduced concepts of damage-response and tolerance frameworks to explain TB induction. These frameworks highlight the key role of an exaggerated and intolerant host response against M. tuberculosis bacilli which induces the classical TB cavity in immunocompetent adults once the constant endogenous reinfection process has resulted in the presence of bacilli in the upper lobes, where they can grow faster and the immune response is delayed. This essay intends to provide new clues to understanding the induction of TB in non-immunosuppressed patients.

  19. The use of genetically marked infection cohorts to study changes in establishment rates during the time course of a repeated Ascaridia galli infection in chickens

    DEFF Research Database (Denmark)

    Ferdushy, Tania; Luna Olivares, Luz Adilia; Nejsum, Peter

    2015-01-01

    This study investigated the changes in establishment rates during the time course of a 6week trickle infection of chickens with Ascaridia galli at two different dose levels, using a molecular marker. To differentiate early and late infection, two different egg cohorts (haplotype a and haplotype b...

  20. Latent tuberculosis in nursing professionals of a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Valim Andréia

    2011-05-01

    Full Text Available Abstract Tuberculosis (TB is considered an occupational disease among health-care workers (HCWs. Direct contact with TB patients leads to an increased risk to become latently infected by Mycobacterium tuberculosis. The objective of this study is to estimate the prevalence of latent M. tuberculosis minfection among nursing professionals of a hospital in Rio Grande do Sul, Brazil, assessed by tuberculin skin test (TST. From November 2009 to May 2010, latent M. tuberculosis infection was assessed by TST in 55 nursing professionals. Epidemiological information was collected using a standardized questionnaire. A positive TST result (> or = 10 mm was observed in 47.3% of the HCWs tested. There was no significant difference in TST positivity when duration of employment or professional category (technician or nurse was evaluated. The results of this work reinforce the need for control measures to prevent latent M. tuberculosis infection among nursing professionals at the hospital where the study was conducted.

  1. Latent and Asymptomatic Toxocara Infection among Young Population in Northwest Iran: The Necessity of Informing People as a Potential Health Risk

    Directory of Open Access Journals (Sweden)

    Tina Momeni

    2016-01-01

    Full Text Available Objectives. This study was designed to determine the frequency of anti-Toxocara antibodies in youngsters aging from 2 to 20 years in northwest Iran. Materials and Methods. 397 samples were taken randomly almost equally from four locations in Urmia, west Azerbaijan, during August 2014 to September 2015. Anti-Toxocara IgG antibody assays were done on sera by using ELISA kit (IBL, Germany. In order to prevent cross-reaction, the samples of the patients who are infected with other parasites in stool exam, especially Ascarididae family, were also excluded. SPSS 16.0 software was used for statistical analysis. Results. 12 (3% of the serum samples were positive for anti-Toxocara IgG. According to the Chi-square analysis, risk factors such as mother’s educational level, keeping dogs or cats as pets, and history of coughing were related to Toxocara infection (P<0.05. There was no relationship between toxocariasis and gender, history of onychophagy, pica, fever, abdominal pain, and anorexia; however, we found a significant relationship between Toxocara infection and chronic coughing (P=0.045. Conclusion. Toxocariasis in northwest Iran can be considered as a public health problem. This study may also help to increase the awareness about this infection.

  2. Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9

    International Nuclear Information System (INIS)

    Keryer-Bibens, Cécile; Pioche-Durieu, Catherine; Villemant, Cécile; Souquère, Sylvie; Nishi, Nozomu; Hirashima, Mitsuomi; Middeldorp, Jaap; Busson, Pierre

    2006-01-01

    Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested. Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking. HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1. This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells

  3. Establishment of an efficient virus-induced gene silencing (VIGS) assay in Arabidopsis by Agrobacterium-mediated rubbing infection.

    Science.gov (United States)

    Manhães, Ana Marcia E de A; de Oliveira, Marcos V V; Shan, Libo

    2015-01-01

    Several VIGS protocols have been established for high-throughput functional genomic screens as it bypasses the time-consuming and laborious process of generation of transgenic plants. The silencing efficiency in this approach is largely hindered by a technically demanding step in which the first pair of newly emerged true leaves at the 2-week-old stage are infiltrated with a needleless syringe. To further optimize VIGS efficiency and achieve rapid inoculation for a large-scale functional genomic study, here we describe a protocol of an efficient VIGS assay in Arabidopsis using Agrobacterium-mediated rubbing infection. The Agrobacterium inoculation is performed by simply rubbing the leaves with Filter Agent Celite(®) 545. The highly efficient and uniform silencing effect was indicated by the development of a visibly albino phenotype due to silencing of the Cloroplastos alterados 1 (CLA1) gene in the newly emerged leaves. In addition, the albino phenotype could be observed in stems and flowers, indicating its potential application for gene functional studies in the late vegetative development and flowering stages.

  4. Establishing support groups for HIV-infected women: using experiences to develop guiding principles for project implementation.

    Science.gov (United States)

    Visser, Maretha J; Mundell, Jonathan P

    2008-07-01

    HIV-infected women need support to deal with their diagnosis as well as with the stigma attached to HIV. As part of their practical training, Master's-level psychology students negotiated with the staff of four clinics in townships in Tshwane, South Africa, to establish support groups for HIV+ women and offered to assist them in facilitating the groups. This study aimed to understand why the implementation of groups was successful in one clinic and not other clinics. The student reports on their experiences and interaction with clinic staff and clients were used as sources of data. Using qualitative data analysis, different dynamics and factors that could affect project implementation were identified in each clinic. The socio-ecological and systems theories were used to understand implementation processes and obstacles in implementation. The metaphor of building a bridge over a gorge was used to describe the different phases in and obstacles to the implementation of the intervention. Valuable lessons were learnt, resulting in the development of guiding principles for the implementation of support groups in community settings.

  5. Dynamic Latent Classification Model

    DEFF Research Database (Denmark)

    Zhong, Shengtong; Martínez, Ana M.; Nielsen, Thomas Dyhre

    as possible. Motivated by this problem setting, we propose a generative model for dynamic classification in continuous domains. At each time point the model can be seen as combining a naive Bayes model with a mixture of factor analyzers (FA). The latent variables of the FA are used to capture the dynamics...

  6. A caprine herpesvirus 1 vaccine adjuvanted with MF59™ protects against vaginal infection and interferes with the establishment of latency in goats.

    Directory of Open Access Journals (Sweden)

    Mariarosaria Marinaro

    Full Text Available The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1 vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN titers. Peripheral blood mononuclear cells (PBMC stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.

  7. A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats

    Science.gov (United States)

    Marinaro, Mariarosaria; Rezza, Giovanni; Del Giudice, Giuseppe; Colao, Valeriana; Tarsitano, Elvira; Camero, Michele; Losurdo, Michele; Buonavoglia, Canio; Tempesta, Maria

    2012-01-01

    The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats. PMID:22511971

  8. Extracellular Hsp90 serves as a co-factor for MAPK activation and latent viral gene expression during de novo infection by KSHV

    International Nuclear Information System (INIS)

    Qin Zhiqiang; DeFee, Michael; Isaacs, Jennifer S.; Parsons, Chris

    2010-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), an important cause of morbidity and mortality in immunocompromised patients. KSHV interaction with the cell membrane triggers activation of specific intracellular signal transduction pathways to facilitate virus entry, nuclear trafficking, and ultimately viral oncogene expression. Extracellular heat shock protein 90 localizes to the cell surface (csHsp90) and facilitates signal transduction in cancer cell lines, but whether csHsp90 assists in the coordination of KSHV gene expression through these or other mechanisms is unknown. Using a recently characterized non-permeable inhibitor specifically targeting csHsp90 and Hsp90-specific antibodies, we show that csHsp90 inhibition suppresses KSHV gene expression during de novo infection, and that this effect is mediated largely through the inhibition of mitogen-activated protein kinase (MAPK) activation by KSHV. Moreover, we show that targeting csHsp90 reduces constitutive MAPK expression and the release of infectious viral particles by patient-derived, KSHV-infected primary effusion lymphoma cells. These data suggest that csHsp90 serves as an important co-factor for KSHV-initiated MAPK activation and provide proof-of-concept for the potential benefit of targeting csHsp90 for the treatment or prevention of KSHV-associated illnesses.

  9. Reactivation of latent HIV-1 by new semi-synthetic ingenol esters

    Energy Technology Data Exchange (ETDEWEB)

    Pandeló José, Diego [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Bartholomeeusen, Koen [Department of Medicine, Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143-0703 (United States); Delveccio da Cunha, Rodrigo; Abreu, Celina Monteiro [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Glinski, Jan [PlantaAnalytica LLC, Danbury, CT 06810 (United States); Barbizan Ferreira da Costa, Thais; Bacchi Rabay, Ana Flávia Mello; Pianowski Filho, Luiz Francisco [Kyolab Laboratories, Valinhos, São Paulo 13273-105 (Brazil); Dudycz, Lech W. [Lex Company Research Laboratories, Shirley 01464, MA (United States); Ranga, Udaykumar [Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064 (India); Peterlin, Boris Matija [Department of Medicine, Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143-0703 (United States); Pianowski, Luiz Francisco [Kyolab Laboratories, Valinhos, São Paulo 13273-105 (Brazil); Tanuri, Amilcar [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Aguiar, Renato Santana, E-mail: santana@biologia.ufrj.br [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil)

    2014-08-15

    The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus reactivation is dependent on intact NF-κB binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin T1. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART. - Highlights: • 3-caproyl-ingenol (ING B) reactivates latent HIV better than SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. • ING B promotes PKC activation and NF-kB translocation to the nucleus. • ING B activates virus transcription of B and non-B subtypes of HIV-1. • ING B activates HIV transcription in infected primary resting CD4+ T cells. • ING B induces higher levels of P-TEFb components in human primary cells.

  10. Urbanization and baseline prevalence of genital infections including Candida, Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as established in the Dutch Cervical Screening Program

    NARCIS (Netherlands)

    Boon, ME; Claasen, HHV; Kok, LP

    OBJECTIVE: An overgrowth of coccoid bacilli in the absence of lactobacilli (bacterial vaginosis) is considered a sign of a "disturbed" vaginal ecologic system. The aim of this study was to establish the baseline prevalence of genital infections and of a disturbed vaginal ecologic system and their

  11. Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection

    NARCIS (Netherlands)

    Rodrigues, Cristina D.; Hannus, Michael; Prudencio, Miguel; Martin, Cecilie; Goncalves, Ligia A.; Portugal, Silvia; Epiphanio, Sabrina; Akinc, Akin; Hadwiger, Philipp; Jahn-Hofmann, Kerstin; Roehl, Ingo; van Gemert, Geert-Jan; Franetich, Jean-Francois; Luty, Adrian J. F.; Sauerwein, Robert; Mazier, Dominique; Koteliansky, Victor; Vornlocher, Hans-Peter; Echeverri, Christophe J.; Mota, Maria M.

    2008-01-01

    An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I

  12. Towards an HIV-1 cure: measuring the latent reservoir

    Science.gov (United States)

    Bruner, Katherine M.; Hosmane, Nina N.; Siliciano, Robert F.

    2015-01-01

    The latent reservoir of HIV-1 in resting memory CD4+ T cells serves as a major barrier to curing HIV-1 infection. While many PCR- and culture-based assays have been used to measure the size of the latent reservoir, correlation between results of different assays is poor and recent studies indicate that no available assay provides an accurate measurement of reservoir size. The discrepancies between assays are a hurdle to clinical trials that aim to measure the efficacy of HIV-1 eradication strategies. Here we describe the advantages and disadvantages of various approaches to measure the latent reservoir. PMID:25747663

  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. The feasibility of the interferon gamma release assay and predictors of discordance with the tuberculin skin test for the diagnosis of latent tuberculosis infection in a remote Aboriginal community.

    Directory of Open Access Journals (Sweden)

    Gonzalo G Alvarez

    Full Text Available The tuberculin skin test (TST is the standard test used to screen for latent TB infection (LTBI in the northern Canadian territory of Nunavut. Interferon gamma release assays (IGRA are T cell blood-based assays to diagnose LTBI. The Bacillus Calmette-Guerin (BCG vaccine is part of the routine immunization schedule in Nunavut. The objective of this study was to test the feasibility, and predictors of discordance between the Tuberculin Skin Test (TST and the IGRA assay in a medically under-serviced remote arctic Aboriginal population.Both the TST and QuantiFERON-TB Gold (Qiagen group IGRA tests were offered to people in their homes as part of a public health campaign aimed at high TB risk residential areas in Iqaluit, Nunavut, Canada. Feasibility was measured by the capacity of the staff to do the test successfully as measured by the proportion of results obtained.In this population of predominantly young Inuit who were mostly BCG vaccinated, the use of IGRA for the diagnosis of LTBI was feasible. IGRA testing resulted in more available test results reaching patients (95.6% vs 90.9% p = 0.02 but took longer (median 8 days (IGRA vs 2 days (TST, p value < 0.0001. 44/256 participants (17.2% had discordant results. Multivariable regression analysis suggested that discordant results were most likely to have received multiple BCG vaccinations (RR 20.03, 95% CI, 3.94-101.82, followed by BCG given post infancy (RR 8.13, 95% CI, 2.54-26.03 and then to a lesser degree when BCG was given in infancy (RR 6.43, 95% CI, 1.72-24.85.IGRA is feasible in Iqaluit, Nunavut, a remote Arctic community. IGRA testing results in more test results available to patients compared to TST. This test could result in fewer patients requiring latent TB treatment among those previously vaccinated with BCG in a region with limited public health human resources.

  15. 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.

  16. 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.

  17. Intrauterine inoculation of minipigs with Chlamydia trachomatis during diestrus establishes a longer lasting infection compared to vaginal inoculation during estrus

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Secher, Jan O

    2017-01-01

    Advanced animal models, such as minipigs, are needed for the development of a globally requested human Chlamydia vaccine. Previous studies have shown that vaginal inoculation of sexually mature Göttingen minipigs with Chlamydia trachomatis resulted in an infection lasting only 3-5 days. The aim...... resulted in a longer lasting infection (at least 10 days) compared to estrus (3-5 days). Furthermore, we found a significant C. trachomatis specific IFN-γ response in pigs inoculated during estrus correlating with the accelerated clearance of infection in these pigs. These findings suggest...

  18. 10 Años innovando en el tratamiento de la infección tuberculosa latente: comparación entre pautas estándar y pautas cortas en tratamiento directamente observado 10 years of innovation in the treatment of latent tuberculosis infection: a comparison between standard and short course therapies in directly observed therapy

    Directory of Open Access Journals (Sweden)

    G. López

    2011-06-01

    cortas 96 (23,41% pacientes, por los siguientes motivos (36 por abandono voluntario, 54 por reacciones adversas, 1 por libertad o traslado, 3 por causa desconocida, 1 por brote psicótico en enfermo psiquiátrico y 1 por hepatitis aguda no filiada. Se aprecian diferencias significativas en las tasas de finalización del TIT al comparar la pauta estándar 9H y las pautas cortas. Se observa una mayor probabilidad de finalización, estadísticamente significativa, con las pautas cortas: p: 0,006; Odds Ratio: 1.56 (LC95%: 1.14-2.12. Este diferencia en la finalización se debe a que la pauta 9H presenta un mayor número de abandonos voluntarios sin motivo aparente (p: 0.002; OR: 2.03 [1.30-3.15] y un mayor número de abandonos por conducción a otro centro o libertad (pObjectives: The main aim of the study is to compare the acceptance, adherence, tolerance and safety of short course therapies in comparison to a standard 9 month treatment for latent tuberculosis infection (LTBI in directly observed therapy (DOT and contrast this with previous results from a standard therapy in patient self-administered treatment. Materials and methods: Retrospective longitudinal study carried out at a medium sized prison. Period of inclusion covers 10 years, from January 2000 to December 2009. The Centers for Disease Control and Prevention (CDC inclusion and exclusion criteria were used, as well as the ones included in the Program for Tuberculosis Prevention and Control in the Prison Environment. 4 LTBI therapies according to the preference of the patient and possible interactions with other treatments were utilised. Therapy I consisted of isoniazid (H in doses of 300 mg/day for 9 months (9H, therapy II with rifampicin for 2 months, twice a week, (2R2Z2 therapy III with rifampicin and isoniazid for 3 months (3RH and therapy IV with rifampicin for four months (4R. Treatment was administered under strict DOT conditions by nursing staff. Results: 902 patients were included, of which 810 accepted

  19. Establishment of HSV1 latency in immunodeficient mice facilitates efficient in vivo reactivation.

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    Chandran Ramakrishna

    2015-03-01

    Full Text Available The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1 infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth understanding of the mechanisms regulating the maintenance of latency and reactivation are essential for developing new approaches to block reactivation. However, the lack of a reliable mouse model that supports efficient in vivo reactivation (IVR resulting in production of infectious HSV1 and/or disease has hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts, we exploited the antiviral and immunomodulatory activities of IVIG (intravenous immunoglobulins to promote survival of latently infected immunodeficient Rag mice. Latently infected Rag mice derived by high dose (HD, but not low dose (LD, HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia stress (HS, the majority of HD inoculated mice developed HSV1 encephalitis (HSE rapidly and synchronously, whereas for LD inoculated mice reactivated HSV1 persisted only transiently in trigeminal ganglia (Tg. T cells, but not B cells, were required to suppress spontaneous reactivation in HD inoculated latently infected mice. Transfer of HSV1 memory but not OVA specific or naïve T cells prior to HS blocked IVR, revealing the utility of this powerful Rag latency model for studying immune mechanisms involved in control of reactivation. Crossing Rag mice to various knockout strains and infecting them with wild type or mutant HSV1 strains is expected to provide novel insights into the role of specific cellular and viral genes in reactivation, thereby facilitating identification of new targets with the potential to block reactivation.

  20. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas

    International Nuclear Information System (INIS)

    Glaser, R.; Zhang, Haizhang; Yao, Kaitai; Zhu, Hecheng; Wang, Fuxi; Li, Guiyuan; Wen, Dongseng; Li, Yingping

    1989-01-01

    Two epithelia tumor cell lines were established from biopsy specimens of nasopharyngeal carcinomas (NPC). The specimens were taken from poorly differentiated squamous cell carcinomas of the nasopharynx. The tissues were prepared for cell culture and eventually two continuous epithelia cell lines were obtained and designated HONE-1 and HNE-1. Light and electron microscopic examination of these two cell lines demonstrated cells with an epithelial morphology including the presence of desmosomes. It was found that early-passage uncloned HNE-1 cells (passage 23) could be superinfected with B95-8 and NPC-EBV isolates as demonstrated by the induction of Epstein-Barr virus (EBV)-specific early antigen(s) in a small percentage of the cells; HONE-1 cells could also be superinfected with EBV. Southern blot analysis detected EBV DNA in samples from uncloned HNE-1 cells at passages 12, 17, 21, 27, and 35. However, by passage 45, EBV DNA could no longer be detected in HNE-1 cells by Southern blot analysis. The EBV genome was detected in parental HONE-1 cells at subculture 9 and in clone 40 cells up to passage 40 thus far. The data suggest that EBV genome-positive HNE-1 and HONE-1 cells were lost as the cells were cultivated in vitro and that cloning the cells at an early passage level may be critical in maintaining EBV genome-positive epithelial NPC cells. These EBV genome-positive epithelia NPC cell lines will be useful for studying the association of EBV and NPC

  1. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection.

    Directory of Open Access Journals (Sweden)

    Matthew D Greseth

    2014-03-01

    Full Text Available The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis. Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia

  2. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection.

    Science.gov (United States)

    Greseth, Matthew D; Traktman, Paula

    2014-03-01

    The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in

  3. Current management options for latent tuberculosis: a review

    Directory of Open Access Journals (Sweden)

    Norton BL

    2012-11-01

    Full Text Available Brianna L Norton, David P HollandDepartment of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USAAbstract: Tuberculosis remains the world’s second leading infectious cause of death, with nearly one-third of the global population latently infected. Treatment of latent tuberculosis infection is a mainstay of tuberculosis-control efforts in low-to medium-incidence countries. Isoniazid monotherapy has been the standard of care for decades, but its utility is impaired by poor completion rates. However, new, shorter-course regimens using rifamycins improve completion rates and are cost-saving compared with standard isoniazid monotherapy. We review the currently available therapies for latent tuberculosis infection and their toxicities and include a brief economic comparison of the different regimens.Keywords: isoniazid, rifampin, rifapentine, tuberculin skin test, interferon-gamma release assay

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

    Science.gov (United States)

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

    2011-01-01

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

  5. Comparative Genomics of Chrysochromulina Ericina Virus and Other Microalga-Infecting Large DNA Viruses Highlights Their Intricate Evolutionary Relationship with the Established Mimiviridae Family.

    Science.gov (United States)

    Gallot-Lavallée, Lucie; Blanc, Guillaume; Claverie, Jean-Michel

    2017-07-15

    Chrysochromulina ericina virus CeV-01B (CeV) was isolated from Norwegian coastal waters in 1998. Its icosahedral particle is 160 nm in diameter and encloses a 474-kb double-stranded DNA (dsDNA) genome. This virus, although infecting a microalga (the haptophyceae Haptolina ericina , formerly Chrysochromulina ericina ), is phylogenetically related to members of the Mimiviridae family, initially established with the acanthamoeba-infecting mimivirus and megavirus as prototypes. This family was later split into two genera ( Mimivirus and Cafeteriavirus ) following the characterization of a virus infecting the heterotrophic stramenopile Cafeteria roenbergensis (CroV). CeV, as well as two of its close relatives, which infect the unicellular photosynthetic eukaryotes Phaeocystis globosa (Phaeocystis globosa virus [PgV]) and Aureococcus anophagefferens (Aureococcus anophagefferens virus [AaV]), are currently unclassified by the International Committee on Viral Taxonomy (ICTV). The detailed comparative analysis of the CeV genome presented here confirms the phylogenetic affinity of this emerging group of microalga-infecting viruses with the Mimiviridae but argues in favor of their classification inside a distinct clade within the family. Although CeV, PgV, and AaV share more common features among them than with the larger Mimiviridae , they also exhibit a large complement of unique genes, attesting to their complex evolutionary history. We identified several gene fusion events and cases of convergent evolution involving independent lateral gene acquisitions. Finally, CeV possesses an unusual number of inteins, some of which are closely related despite being inserted in nonhomologous genes. This appears to contradict the paradigm of allele-specific inteins and suggests that the Mimiviridae are especially efficient in spreading inteins while enlarging their repertoire of homing genes. IMPORTANCE Although it infects the microalga Chrysochromulina ericina , CeV is more closely

  6. [Comparative study of concordance and costs between tuberculin skin test and QuantiFERON(®)-TB Gold In-Tube in the diagnosis of latent tuberculosis infection among contacts of patients with pulmonary tuberculosis].

    Science.gov (United States)

    Martinez Lacasa, Xavier; Canals Font, Roser; Jaen Manzanera, Angels; Cuchi Burgos, Eva; Lite Lite, Josep

    2015-11-20

    Recently diagnosis of latent tuberculosis infection (LTBI) can be made using the tuberculin skin test (TST) or by techniques known as interferon-γ release assays (IGRAS), being QuantiFERON(®)-TB Gold In-Tube (QF-G-IT) the most used. The IGRAS avoid some drawbacks of the TST, especially cross-reaction with bacillus Calmette-Guérin (BCG) vaccine, but also present some problems such as those arising from cost and the need of having an adequate infrastructure and experience. There is no clear consensus on which technique should be preferentially used for the diagnosis of LTBI. This is a comparative study between the TST and QT-G-IT in a cohort of contacts of patients with pulmonary tuberculosis during the study period. An analysis of global agreement and groups was performed according to whether the contacts were vaccinated with BCG or not. A study of costs of both techniques and diagnostic strategies based on these techniques was performed. The agreement between TST and QF-G-IT was acceptable in the whole sample yet it was very good in the unvaccinated group. Few cases of indeterminate values were recorded. The cost study showed that TST was cheaper than QF-G-IT; however when we analyzed the cost of the strategies according to each technique, the QF-G-IT showed a better cost-benefit. We suggest considering QF-G-IT as the only preferred technique for the diagnosis of LTBI in household contacts, based on good overall agreement between the 2 techniques (even if we eliminate the effect of the vaccine) and a cost analysis favorable to QF-G-IT. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  7. Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Simon G. Kimuda

    2017-01-01

    Full Text Available Latent tuberculosis infection (LTBI is evidence of immunological control of tuberculosis. Dormancy survival regulator (DosR regulon-encoded proteins may have a role in the maintenance of LTBI. T cell responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were found to be most frequent among household contacts of TB cases from Uganda compared to other DosR proteins, but antibody responses were not described. We characterized antibody responses to these proteins in individuals from Uganda. Antibodies to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were measured in 68 uninfected individuals, 62 with LTBI, and 107 with active pulmonary tuberculosis (APTB cases. There were no differences in the concentrations of antibodies to Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins between individuals with LTBI and APTB and those who were uninfected. LTBI was associated with higher concentrations of antibodies to Rv1733c in female participants [adjusted geometric mean ratio: 1.812, 95% confidence interval (CI: 1.105 2.973, and p=0.019] but not in males (p value for interaction = 0.060. Antibodies to the four DosR regulon-encoded proteins investigated may not serve as good biomarkers of LTBI in the general population. More of the M.tb proteome needs to be screened to identify proteins that induce strong antibody responses in LTBI.

  8. Latent Microsporidiosis Caused by Encephalitozoon cuniculi in Immunocompetent Hosts: A Murine Model Demonstrating the Ineffectiveness of the Immune System and Treatment with Albendazole

    Science.gov (United States)

    Kotkova, Michaela; Sak, Bohumil; Kvetonova, Dana; Kvac, Martin

    2013-01-01

    Background Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. Aims To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. Methods Mice were per orally infected with 107 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host’s organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. Results Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. Conclusion Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of

  9. Latent microsporidiosis caused by Encephalitozoon cuniculi in immunocompetent hosts: a murine model demonstrating the ineffectiveness of the immune system and treatment with albendazole.

    Directory of Open Access Journals (Sweden)

    Michaela Kotkova

    Full Text Available BACKGROUND: Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. AIMS: To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. METHODS: Mice were per orally infected with 10(7 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host's organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. RESULTS: Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. CONCLUSION: Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings

  10. Bioactive activities of natural products against herpesvirus infection.

    Science.gov (United States)

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

  11. Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

    Science.gov (United States)

    Richards, Katherine A; DiPiazza, Anthony T; Rattan, Ajitanuj; Knowlden, Zackery A G; Yang, Hongmei; Sant, Andrea J

    2018-01-01

    One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified. We found that a very diverse specificity of CD4 T cells is primed by infection, including epitopes from hemagglutinin, neuraminidase, matrix protein, nucleoprotein, and non-structural protein-1. Using peptide-specific cytokine EliSpots, the diversity and immunodominance hierarchies established in the lung-draining lymph node were compared with specificities of CD4 T cells that home to the lung. Our studies revealed that CD4 T cells of all epitope specificities identified in peripheral lymphoid tissue home back to the lung and that most of these lung-homing cells are localized within the tissue rather than the pulmonary vasculature. There is a striking shift of CD4 T cell functionality that enriches for IFN-γ production as cells are primed in the lymph node, enter the lung vasculature, and finally establish residency in the tissue, but with no apparent shifts in their functional avidity. We conclude that CD4 T cells of broad viral epitope specificity are recruited into the lung after influenza infection, where they then have the opportunity to encounter infected or antigen-bearing antigen-presenting cells.

  12. Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection

    DEFF Research Database (Denmark)

    Song, Z; Kong, K F; Wu, H

    2010-01-01

    Virulent factors produced by pathogens play an important role in the infectious process, which is regulated by a cell-to-cell communication mechanism called quorum sensing (QS). Pseudomonas aeruginosa is an important opportunistic human pathogen, which causes infections in patients with compromis...

  13. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2017-04-01

    . As the generation of Tfh are important for establishing effective immune responses during primary infections, Tfh are likely to be an early target of HIV-1 following transmission, creating an important component of the reservoir that has the potential to expand over time.

  14. Latent semantic analysis.

    Science.gov (United States)

    Evangelopoulos, Nicholas E

    2013-11-01

    This article reviews latent semantic analysis (LSA), a theory of meaning as well as a method for extracting that meaning from passages of text, based on statistical computations over a collection of documents. LSA as a theory of meaning defines a latent semantic space where documents and individual words are represented as vectors. LSA as a computational technique uses linear algebra to extract dimensions that represent that space. This representation enables the computation of similarity among terms and documents, categorization of terms and documents, and summarization of large collections of documents using automated procedures that mimic the way humans perform similar cognitive tasks. We present some technical details, various illustrative examples, and discuss a number of applications from linguistics, psychology, cognitive science, education, information science, and analysis of textual data in general. WIREs Cogn Sci 2013, 4:683-692. doi: 10.1002/wcs.1254 CONFLICT OF INTEREST: The author has declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

  15. Latent heat coldness storage; Stockage du froid par chaleur latente

    Energy Technology Data Exchange (ETDEWEB)

    Dumas, J.P. [Pau Univ., Lab. de Thermodynamique et Energetique, LTE, 64 (France)

    2002-07-01

    This article presents the advantages of latent heat storage systems which use the solid-liquid phase transformation of a pure substance or of a solution. The three main methods of latent heat storage of coldness are presented: ice boxes, encapsulated nodules, and ice flows: 1 - definition of the thermal energy storage (sensible heat, latent heat, thermochemical storage); 2 - advantages and drawbacks of latent heat storage; 3 - choice criteria for a phase-change material; 4 - phenomenological aspect of liquid-solid transformations (phase equilibrium, crystallisation and surfusion); 5 - different latent heat storage processes (ice boxes, encapsulated nodules, two-phase refrigerating fluids); 6 - ice boxes (internal and external melting, loop, air injection, measurement of ice thickness); 7 - encapsulated nodules (nodules, tank, drainage, advantage and drawbacks, charge and discharge); 8 - two-phase refrigerating fluids (composition, ice fabrication, flow circulation, flow storage, exchangers). (J.S.)

  16. Established Population of Blacklegged Ticks with High Infection Prevalence for the Lyme Disease Bacterium, Borrelia burgdorferi Sensu Lato, on Corkscrew Island, Kenora District, Ontario

    Science.gov (United States)

    Scott, John D.; Foley, Janet E.; Clark, Kerry L.; Anderson, John F.; Durden, Lance A.; Manord, Jodi M.; Smith, Morgan L.

    2016-01-01

    We document an established population of blacklegged ticks, Ixodes scapularis, on Corkscrew Island, Kenora District, Ontario, Canada. Primers of the outer surface protein A (OspA) gene, the flagellin (fla) gene, and the flagellin B (flaB) gene were used in the PCR assays to detect Borrelia burgdorferi sensu lato (s.l.), the Lyme disease bacterium. In all, 60 (73%) of 82 adult I. scapularis, were infected with B. burgdorferi s.l. As well, 6 (43%) of 14 unfed I. scapularis nymphs were positive for B. burgdorferi s.l. An I. scapularis larva was also collected from a deer mouse, and several unfed larvae were gathered by flagging leaf litter. Based on DNA sequencing of randomly selected Borrelia amplicons from six nymphal and adult I. scapularis ticks, primers for the flagellin (fla) and flagellin B (flaB) genes reveal the presence of B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. We collected all 3 host-feeding life stages of I. scapularis in a single year, and report the northernmost established population of I. scapularis in Ontario. Corkscrew Island is hyperendemic for Lyme disease and has the highest prevalence of B. burgdorferi s.l. for any established population in Canada. Because of this very high infection prevalence, this population of I. scapularis has likely been established for decades. Of epidemiological significance, cottage owners, island visitors, outdoors enthusiasts, and medical professionals must be vigilant that B. burgdorferi s.l.-infected I. scapularis on Corkscrew Island pose a serious public health risk. PMID:27877080

  17. Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1

    Science.gov (United States)

    Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Kagaayi, Joseph; Kizza, Allan; Pillay, Visva; Laeyendecker, Oliver; Reynolds, Steven J.; Eshleman, Susan H.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.

    2009-01-01

    Background Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4+ T cells, potentially complicating future treatment. Methods Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4+ T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. PMID:19338474

  18. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

    Science.gov (United States)

    Deng, Kai; Pertea, Mihaela; Rongvaux, Anthony; Wang, Leyao; Durand, Christine M.; Ghiaur, Gabriel; Lai, Jun; McHugh, Holly L.; Hao, Haiping; Zhang, Hao; Margolick, Joseph B.; Gurer, Cagan; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Deeks, Steven G.; Strowig, Till; Kumar, Priti; Siliciano, Janet D.; Salzberg, Steven L.; Flavell, Richard A.; Shan, Liang; Siliciano, Robert F.

    2015-01-01

    Despite antiretroviral therapy (ART), HIV-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6–8. A key remaining question is whether virus-specific immune mechanisms including cytolytic T lymphocytes (CTL) can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir. PMID:25561180

  19. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

    Science.gov (United States)

    Cook, R. Frank; Eberth, John; Chelvarajan, R. Lakshman; Artiushin, Sergey; Timoney, Peter J.

    2016-01-01

    Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and Eq

  20. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion.

    Directory of Open Access Journals (Sweden)

    Sanjay Sarkar

    2016-12-01

    Full Text Available Equine arteritis virus (EAV is the causative agent of equine viral arteritis (EVA, a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10-70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16 that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1 having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001 and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence in the male reproductive tract. EqCXCL16Sa and

  1. Trypanosome infection establishment in the tsetse fly gut is influenced by microbiome-regulated host immune barriers.

    Directory of Open Access Journals (Sweden)

    Brian L Weiss

    Full Text Available Tsetse flies (Glossina spp. vector pathogenic African trypanosomes, which cause sleeping sickness in humans and nagana in domesticated animals. Additionally, tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology. Tsetse is highly resistant to infection with trypanosomes, and this phenotype depends on multiple physiological factors at the time of challenge. These factors include host age, density of maternally-derived trypanolytic effector molecules present in the gut, and symbiont status during development. In this study, we investigated the molecular mechanisms that result in tsetse's resistance to trypanosomes. We found that following parasite challenge, young susceptible tsetse present a highly attenuated immune response. In contrast, mature refractory flies express higher levels of genes associated with humoral (attacin and pgrp-lb and epithelial (inducible nitric oxide synthase and dual oxidase immunity. Additionally, we discovered that tsetse must harbor its endogenous microbiome during intrauterine larval development in order to present a parasite refractory phenotype during adulthood. Interestingly, mature aposymbiotic flies (Gmm(Apo present a strong immune response earlier in the infection process than do WT flies that harbor symbiotic bacteria throughout their entire lifecycle. However, this early response fails to confer significant resistance to trypanosomes. Gmm(Apo adults present a structurally compromised peritrophic matrix (PM, which lines the fly midgut and serves as a physical barrier that separates luminal contents from immune responsive epithelial cells. We propose that the early immune response we observe in Gmm(Apo flies following parasite challenge results from the premature exposure of gut epithelia to parasite-derived immunogens in the absence of a robust PM. Thus, tsetse's PM appears to regulate the timing of host immune induction following parasite challenge. Our results

  2. Identification of candidate agents active against N. ceranae infection in honey bees: establishment of a medium throughput screening assay based on N. ceranae infected cultured cells.

    Science.gov (United States)

    Gisder, Sebastian; Genersch, Elke

    2015-01-01

    Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera) and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana) but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin) or presumed (surfactin) or no (paromomycin) activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole) totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae.

  3. Identification of candidate agents active against N. ceranae infection in honey bees: establishment of a medium throughput screening assay based on N. ceranae infected cultured cells.

    Directory of Open Access Journals (Sweden)

    Sebastian Gisder

    Full Text Available Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin or presumed (surfactin or no (paromomycin activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae.

  4. Prevalence and risk factors of latent Tuberculosis among ...

    African Journals Online (AJOL)

    termine the risk factors of prevalent LTBI. We used a mixed effects binomial model with a logarithmic link function to estimate prevalence ratios (PR) for risk fac- tors of latent tuberculosis infection (LTBI). Ethical consideration. The study was approved by the Makerere University. School of Public Health–Higher Degrees and ...

  5. Viral infection of implanted meningeal tumors induces antitumor memory T-cells to travel to the brain and eliminate established tumors.

    Science.gov (United States)

    Gao, Yanhua; Whitaker-Dowling, Patricia; Barmada, Mamdouha A; Basse, Per H; Bergman, Ira

    2015-04-01

    Leptomeningeal metastases occur in 2%-5% of patients with breast cancer and have an exceptionally poor prognosis. The blood-brain and blood-meningeal barriers severely inhibit successful chemotherapy. We have developed a straightforward method to induce antitumor memory T-cells using a Her2/neu targeted vesicular stomatitis virus. We sought to determine whether viral infection of meningeal tumor could attract antitumor memory T-cells to eradicate the tumors. Meningeal implants in mice were studied using treatment trials and analyses of immune cells in the tumors. This paper demonstrates that there is a blood-meningeal barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier can be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cell transfer resulted in 89% cure of meningeal tumor in 2 different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Finally, this paper shows that successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the meninges of these same animals. These results support the hypothesis that a virally based immunization strategy can be used to both prevent and treat meningeal metastases. The meningeal barriers to cancer therapy may be much more permeable to treatment based on cells than treatment based on drugs or molecules. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Longitudinal Research with Latent Variables

    CERN Document Server

    van Montfort, Kees; Satorra, Albert

    2010-01-01

    This book combines longitudinal research and latent variable research, i.e. it explains how longitudinal studies with objectives formulated in terms of latent variables should be carried out, with an emphasis on detailing how the methods are applied. Because longitudinal research with latent variables currently utilizes different approaches with different histories, different types of research questions, and different computer programs to perform the analysis, the book is divided into nine chapters. Starting from some background information about the specific approach, short history and the ma

  7. 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

  8. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Philana Ling Lin

    2016-07-01

    Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

  9. Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

    Science.gov (United States)

    Chen, Shulin; Lai, Yanzhen; He, Zhengqiang; Li, Jianpei; He, Xia; Shen, Rui; Ding, Qiuying; Chen, Hao; Peng, Songguo; Liu, Wanli

    2018-05-04

    This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P  20.0). The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

  10. Integrated mapping of establishment risk for emerging vector-borne infections: a case study of canine leishmaniasis in southwest France.

    Directory of Open Access Journals (Sweden)

    Nienke Hartemink

    Full Text Available BACKGROUND: Zoonotic visceral leishmaniasis is endemic in the Mediterranean Basin, where the dog is the main reservoir host. The disease's causative agent, Leishmania infantum, is transmitted by blood-feeding female sandflies. This paper reports an integrative study of canine leishmaniasis in a region of France spanning the southwest Massif Central and the northeast Pyrenees, where the vectors are the sandflies Phlebotomus ariasi and P. perniciosus. METHODS: Sandflies were sampled in 2005 using sticky traps placed uniformly over an area of approximately 100 by 150 km. High- and low-resolution satellite data for the area were combined to construct a model of the sandfly data, which was then used to predict sandfly abundance throughout the area on a pixel by pixel basis (resolution of c. 1 km. Using literature- and expert-derived estimates of other variables and parameters, a spatially explicit R(0 map for leishmaniasis was constructed within a Geographical Information System. R(0 is a measure of the risk of establishment of a disease in an area, and it also correlates with the amount of control needed to stop transmission. CONCLUSIONS: To our knowledge, this is the first analysis that combines a vector abundance prediction model, based on remotely-sensed variables measured at different levels of spatial resolution, with a fully mechanistic process-based temperature-dependent R(0 model. The resulting maps should be considered as proofs-of-principle rather than as ready-to-use risk maps, since validation is currently not possible. The described approach, based on integrating several modeling methods, provides a useful new set of tools for the study of the risk of outbreaks of vector-borne diseases.

  11. Needle autopsy to establish the cause of death in HIV-infected hospitalized adults in Uganda: a comparison to complete autopsy.

    Science.gov (United States)

    Cox, Janneke A; Lukande, Robert L; Kalungi, Sam; Van Marck, Eric; Van de Vijver, Koen; Kambugu, Andrew; Nelson, Ann M; Manabe, Yukari C; Colebunders, Robert

    2014-10-01

    Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda. We subsequently performed a blind and ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected adults who died during hospitalization. Two teams of pathologists reviewed the tissue from either the needle autopsies or the complete autopsy and formulated the major diagnoses, that is, diseases directly contributing to death. The primary outcome was concordance in major diagnosis between needle and complete autopsies. We performed 96 blind needle and complete autopsies and 95 ultrasound-guided needle autopsies. Concordance in major diagnosis between blind needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis (TB) concordance was higher (71%; P autopsy identified at least 1 major diagnosis in 60% of patients; and in 46%, there was complete concordance for all major diagnoses. The main reason for discordance was sampling error of the lesion. Concordance with the addition of ultrasound guidance was 52% for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in tissue cores from the liver (76%) and the spleen (82%). Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB.

  12. Latent geometry of bipartite networks

    Science.gov (United States)

    Kitsak, Maksim; Papadopoulos, Fragkiskos; Krioukov, Dmitri

    2017-03-01

    Despite the abundance of bipartite networked systems, their organizing principles are less studied compared to unipartite networks. Bipartite networks are often analyzed after projecting them onto one of the two sets of nodes. As a result of the projection, nodes of the same set are linked together if they have at least one neighbor in common in the bipartite network. Even though these projections allow one to study bipartite networks using tools developed for unipartite networks, one-mode projections lead to significant loss of information and artificial inflation of the projected network with fully connected subgraphs. Here we pursue a different approach for analyzing bipartite systems that is based on the observation that such systems have a latent metric structure: network nodes are points in a latent metric space, while connections are more likely to form between nodes separated by shorter distances. This approach has been developed for unipartite networks, and relatively little is known about its applicability to bipartite systems. Here, we fully analyze a simple latent-geometric model of bipartite networks and show that this model explains the peculiar structural properties of many real bipartite systems, including the distributions of common neighbors and bipartite clustering. We also analyze the geometric information loss in one-mode projections in this model and propose an efficient method to infer the latent pairwise distances between nodes. Uncovering the latent geometry underlying real bipartite networks can find applications in diverse domains, ranging from constructing efficient recommender systems to understanding cell metabolism.

  13. The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

    Science.gov (United States)

    Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.; Siliciano, Robert F.

    2016-01-01

    Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID:27382129

  14. Association between latent toxoplasmosis and cognition in adults: a cross-sectional study.

    Science.gov (United States)

    Gale, S D; Brown, B L; Erickson, L D; Berrett, A; Hedges, D W

    2015-04-01

    Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

  15. Rapid detection of drug metabolites in latent fingermarks.

    Science.gov (United States)

    Hazarika, Pompi; Jickells, Sue M; Russell, David A

    2009-01-01

    Magnetic particles functionalised with anti-cotinine antibody have been used to image latent fingermarks through the detection of the cotinine antigen in the sweat deposited within the fingerprints of smokers. The antibody-magnetic particle conjugates are readily applied to latent fingerprints while excess reagents are removed through the use of a magnetic wand. The results have shown that drug metabolites, such as cotinine, can be detected and used to image the fingermark to establish the identity of an individual within 15 minutes.

  16. Prevalence of latent alpha-herpesviruses in Thoroughbred racing horses.

    Science.gov (United States)

    Pusterla, Nicola; Mapes, Samantha; David Wilson, W

    2012-08-01

    The objective of this study was to detect and characterize latent equine herpes virus (EHV)-1 and -4 from the submandibular (SMLN) and bronchial lymph (BLN) nodes, as well as from the trigeminal ganglia (TG) of 70 racing Thoroughbred horses submitted for necropsy following sustaining serious musculoskeletal injuries while racing. A combination of nucleic acid precipitation and pre-amplification steps was used to increase analytical sensitivity. Tissues were deemed positive for latent EHV-1 and/or -4 infection when found PCR positive for the corresponding glycoprotein B (gB) gene in the absence of detectable late structural protein gene (gB gene) mRNA. The EHV-1 genotype was also determined using a discriminatory real-time PCR assay targeting the DNA polymerase gene (ORF 30). Eighteen (25.7%) and 58 (82.8%) horses were PCR positive for the gB gene of EHV-1 and -4, respectively, in at least one of the three tissues sampled. Twelve horses were dually infected with EHV-1 and -4, two carried a latent neurotropic strain of EHV-1, six carried a non-neurotropic genotype of EHV-1 and 10 were dually infected with neurotropic and non-neurotropic EHV-1. The distribution of latent EHV-1 and -4 infection varied in the samples, with the TG found to be most commonly infected. Overall, non-neurotropic strains were more frequently detected than neurotropic strains, supporting the general consensus that non-neurotropic strains are more prevalent in horse populations, and hence the uncommon occurrence of equine herpes myeloencephalopathy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Assessing Trust and Effectiveness in Virtual Teams: Latent Growth Curve and Latent Change Score Models

    Directory of Open Access Journals (Sweden)

    Michael D. Coovert

    2017-08-01

    Full Text Available Trust plays a central role in the effectiveness of work groups and teams. This is the case for both face-to-face and virtual teams. Yet little is known about the development of trust in virtual teams. We examined cognitive and affective trust and their relationship to team effectiveness as reflected through satisfaction with one’s team and task performance. Latent growth curve analysis reveals both trust types start at a significant level with individual differences in that initial level. Cognitive trust follows a linear growth pattern while affective trust is overall non-linear, but becomes linear once established. Latent change score models are utilized to examine change in trust and also its relationship with satisfaction with the team and team performance. In examining only change in trust and its relationship to satisfaction there appears to be a straightforward influence of trust on satisfaction and satisfaction on trust. However, when incorporated into a bivariate coupling latent change model the dynamics of the relationship are revealed. A similar pattern holds for trust and task performance; however, in the bivariate coupling change model a more parsimonious representation is preferred.

  18. Latent class models for classification

    NARCIS (Netherlands)

    Vermunt, J.K.; Magidson, J.

    2003-01-01

    An overview is provided of recent developments in the use of latent class (LC) and other types of finite mixture models for classification purposes. Several extensions of existing models are presented. Two basic types of LC models for classification are defined: supervised and unsupervised

  19. 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

  20. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

    Science.gov (United States)

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-06-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

  1. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

    Directory of Open Access Journals (Sweden)

    André Daher

    2015-06-01

    Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

  2. Tsetse GmmSRPN10 has anti-complement activity and is important for successful establishment of trypanosome infections in the fly midgut.

    Directory of Open Access Journals (Sweden)

    Cher-Pheng Ooi

    2015-01-01

    Full Text Available The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2-4 days. In this study, we identified four tsetse (Glossina morsitans morsitans serine protease inhibitors (serpins from a midgut expressed sequence tag (EST library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10 and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission.

  3. Tsetse GmmSRPN10 has anti-complement activity and is important for successful establishment of trypanosome infections in the fly midgut.

    Science.gov (United States)

    Ooi, Cher-Pheng; Haines, Lee R; Southern, Daniel M; Lehane, Michael J; Acosta-Serrano, Alvaro

    2015-01-01

    The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2-4 days. In this study, we identified four tsetse (Glossina morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission.

  4. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  5. Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

    Science.gov (United States)

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

  6. 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

  7. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay.

    Directory of Open Access Journals (Sweden)

    Gregory M Laird

    Full Text Available HIV-1 persists in infected individuals in a stable pool of resting CD4(+ T cells as a latent but replication-competent provirus. This latent reservoir is the major barrier to the eradication of HIV-1. Clinical trials are currently underway investigating the effects of latency-disrupting compounds on the persistence of the latent reservoir in infected individuals. To accurately assess the effects of such compounds, accurate assays to measure the frequency of latently infected cells are essential. The development of a simpler assay for the latent reservoir has been identified as a major AIDS research priority. We report here the development and validation of a rapid viral outgrowth assay that quantifies the frequency of cells that can release replication-competent virus following cellular activation. This new assay utilizes bead and column-based purification of resting CD4(+ T cells from the peripheral blood of HIV-1 infected patients rather than cell sorting to obtain comparable resting CD4(+ T cell purity. This new assay also utilizes the MOLT-4/CCR5 cell line for viral expansion, producing statistically comparable measurements of the frequency of latent HIV-1 infection. Finally, this new assay employs a novel quantitative RT-PCR specific for polyadenylated HIV-1 RNA for virus detection, which we demonstrate is a more sensitive and cost-effective method to detect HIV-1 replication than expensive commercial ELISA detection methods. The reductions in both labor and cost make this assay suitable for quantifying the frequency of latently infected cells in clinical trials of HIV-1 eradication strategies.

  8. Experimental Examination of Bacteriophage Latent-Period Evolution as a Response to Bacterial Availability

    OpenAIRE

    Abedon, Stephen T.; Hyman, Paul; Thomas, Cameron

    2003-01-01

    For obligately lytic bacteriophage (phage) a trade-off exists between fecundity (burst size) and latent period (a component of generation time). This trade-off occurs because release of phage progeny from infected bacteria coincides with destruction of the machinery necessary to produce more phage progeny. Here we employ phage mutants to explore issues of phage latent-period evolution as a function of the density of phage-susceptible bacteria. Theory suggests that higher bacterial densities s...

  9. A coarse to fine minutiae-based latent palmprint matching.

    Science.gov (United States)

    Liu, Eryun; Jain, Anil K; Tian, Jie

    2013-10-01

    With the availability of live-scan palmprint technology, high resolution palmprint recognition has started to receive significant attention in forensics and law enforcement. In forensic applications, latent palmprints provide critical evidence as it is estimated that about 30 percent of the latents recovered at crime scenes are those of palms. Most of the available high-resolution palmprint matching algorithms essentially follow the minutiae-based fingerprint matching strategy. Considering the large number of minutiae (about 1,000 minutiae in a full palmprint compared to about 100 minutiae in a rolled fingerprint) and large area of foreground region in full palmprints, novel strategies need to be developed for efficient and robust latent palmprint matching. In this paper, a coarse to fine matching strategy based on minutiae clustering and minutiae match propagation is designed specifically for palmprint matching. To deal with the large number of minutiae, a local feature-based minutiae clustering algorithm is designed to cluster minutiae into several groups such that minutiae belonging to the same group have similar local characteristics. The coarse matching is then performed within each cluster to establish initial minutiae correspondences between two palmprints. Starting with each initial correspondence, a minutiae match propagation algorithm searches for mated minutiae in the full palmprint. The proposed palmprint matching algorithm has been evaluated on a latent-to-full palmprint database consisting of 446 latents and 12,489 background full prints. The matching results show a rank-1 identification accuracy of 79.4 percent, which is significantly higher than the 60.8 percent identification accuracy of a state-of-the-art latent palmprint matching algorithm on the same latent database. The average computation time of our algorithm for a single latent-to-full match is about 141 ms for genuine match and 50 ms for impostor match, on a Windows XP desktop system with 2

  10. [Topical immunomodulation in the treatment of herpetic infections in HIV-infected patients].

    Science.gov (United States)

    Shul'diakov, A A; Barkhatova, T S; Zubareva, E V; Satarova, S A; Perminova, T A

    2012-01-01

    The efficiency of cycloferon liniment in combined treatment of herpetic infection in patients with latent form of HIV infection has been assess by observations of 40 patients divided into two groups. In the first group, the standard treatment was supplemented with the application of cycloferon liniment twice a day during 7 days; in the second group, the therapy was conducted according to standard recommendations. It was established that the application of cycloferon liniment in combination with standard therapy in patients with relapse of herpetic infection against the background of HIV infection ensures faster disappearance of general infectious syndrome, decreases the period of eruptions and the duration of local inflammations, and accelerates the epithelialization of erosions.

  11. Latent semantics as cognitive components

    DEFF Research Database (Denmark)

    Petersen, Michael Kai; Mørup, Morten; Hansen, Lars Kai

    2010-01-01

    Cognitive component analysis, defined as an unsupervised learning of features resembling human comprehension, suggests that the sensory structures we perceive might often be modeled by reducing dimensionality and treating objects in space and time as linear mixtures incorporating sparsity...... emotional responses can be encoded in words, we propose a simplified cognitive approach to model how we perceive media. Representing song lyrics in a vector space of reduced dimensionality using LSA, we combine bottom-up defined term distances with affective adjectives, that top-down constrain the latent......, which we suggest might function as cognitive components for perceiving the underlying structure in lyrics....

  12. Murid herpesvirus-4 exploits dendritic cells to infect B cells.

    Directory of Open Access Journals (Sweden)

    Miguel Gaspar

    2011-11-01

    Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

  13. Infection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008350 A comparative evaluation of enzyme linked immunospot assay and IS6110 polymerase chain reaction for early diagnosis of tuberculous meningitis. QUAN Chao(全超), et al. Dept Neurol, Huashan Hosp, Shanghai, Med Coll, Fudan Univ, Shanghai 200040. Chin J Neurol 2008;41(3):176-179.Objective To establish an early diagnostic testfor tuberculous meningitis(TBM)with good sensitivity and specificity.Methods Twenty-five patients with a clinical

  14. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.

    Science.gov (United States)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J

    2009-11-12

    Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.

  15. The Latent Structure of Autistic Traits: A Taxometric, Latent Class and Latent Profile Analysis of the Adult Autism Spectrum Quotient

    Science.gov (United States)

    James, Richard J.; Dubey, Indu; Smith, Danielle; Ropar, Danielle; Tunney, Richard J.

    2016-01-01

    Autistic traits are widely thought to operate along a continuum. A taxometric analysis of Adult Autism Spectrum Quotient data was conducted to test this assumption, finding little support but identifying a high severity taxon. To understand this further, latent class and latent profile models were estimated that indicated the presence of six…

  16. 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.

  17. Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

    Science.gov (United States)

    Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

    2018-01-01

    Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

  18. Latent variable models are network models.

    Science.gov (United States)

    Molenaar, Peter C M

    2010-06-01

    Cramer et al. present an original and interesting network perspective on comorbidity and contrast this perspective with a more traditional interpretation of comorbidity in terms of latent variable theory. My commentary focuses on the relationship between the two perspectives; that is, it aims to qualify the presumed contrast between interpretations in terms of networks and latent variables.

  19. Learning Latent Vector Spaces for Product Search

    NARCIS (Netherlands)

    Van Gysel, C.; de Rijke, M.; Kanoulas, E.

    2016-01-01

    We introduce a novel latent vector space model that jointly learns the latent representations of words, e-commerce products and a mapping between the two without the need for explicit annotations. The power of the model lies in its ability to directly model the discriminative relation between

  20. Plutonium and latent nuclear proliferation

    International Nuclear Information System (INIS)

    Quester, G.H.

    1992-01-01

    A country producing nuclear electric power acquires an ability to produce atomic bombs quite easily and without taking many steps beyond that which would be perfectly normal for civilian purposes. The role of plutonium in the three fold list of the gains that must be sought in arms control formulated by Schelling and Halpevin are discussed. On the first, that we should seek to reduce the likelihood of war, it can be argued that plutonium reduces the likelihood in some cases. The second, that we should seek to reduce the destruction in war, is made worse by plutonium. On the third criterion, that we should seek to reduce the burdens in peacetime of everyone's being prepared for war, the situation is confusing and depends on the prospects for nuclear electrical power. It is concluded that latent capability to produce nuclear weapons may be sufficient without the need for actual detonations and deployment of bombs. (UK)

  1. Stability of latent class segments over time

    DEFF Research Database (Denmark)

    Mueller, Simone

    2011-01-01

    Dynamic stability, as the degree to which identified segments at a given time remain unchanged over time in terms of number, size and profile, is a desirable segment property which has received limited attention so far. This study addresses the question to what degree latent classes identified from...... logit model suggests significant changes in the price sensitivity and the utility from environmental claims between both experimental waves. A pooled scale adjusted latent class model is estimated jointly over both waves and the relative size of latent classes is compared across waves, resulting...... in significant differences in the size of two out of seven classes. These differences can largely be accounted for by the changes on the aggregated level. The relative size of latent classes is correlated at 0.52, suggesting a fair robustness. An ex-post characterisation of latent classes by behavioural...

  2. A novel Cre recombinase imaging system for tracking lymphotropic virus infection in vivo.

    Directory of Open Access Journals (Sweden)

    Bernadette M Dutia

    2009-08-01

    Full Text Available Detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. However, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. We have designed a novel Cre recombinase (Cre-based murine system to overcome these problems, and thereby enable tracking and isolation of individual in vivo infected cells.Murine gammaherpesvirus 68 (MHV-68 was used as a prototypic persistent model virus. A Cre expressing recombinant virus was constructed and characterised. The virus is attenuated both in lytic virus replication, producing ten-fold lower lung virus titres than wild type virus, and in the establishment of latency. However, despite this limitation, when the sEGFP7 mouse line containing a Cre-activated enhanced green fluorescent protein (EGFP was infected with the Cre expressing virus, sites of latent and persistent virus infection could be identified within B cells and macrophages of the lymphoid system on the basis of EGFP expression. Importantly, the use of the sEGFP7 mouse line which expresses high levels of EGFP allowed individual virus positive cells to be purified by FACSorting. Virus gene expression could be detected in these cells. Low numbers of EGFP positive cells could also be detected in the bone marrow.The use of this novel Cre-based virus/mouse system allowed identification of individual latently infected cells in vivo and may be useful for the study and long-term monitoring of other latent/persistent virus infections.

  3. Plerocercoids of the cestode Diphyllobothrium ditremum in brown trout Salmo trutta: substantial increase in infection after establishment of European minnow Phoxinus phoxinus.

    Science.gov (United States)

    Borgstrøm, R; Trømborg, J; Haugen, T O; Rosseland, B O

    2017-09-01

    This study focuses on plerocercoids of the cestode Diphyllobothrium ditremum in brown trout Salmo trutta from the subalpine lake Øvre Heimdalsvatn in south-central Norway. Salmo trutta was the only fish species in this lake until European minnow Phoxinus phoxinus was registered in 1969. The P. phoxinus population increased substantially in the following years. In contrast with the 1969-1972 period, when plerocercoids of D. ditremum were practically absent in S. trutta, there was a high prevalence and intensity of infection in the 2013 S. trutta samples. Because the life cycle of D. ditremum involves two larval stages, in copepods and salmonids and mature worms in piscivorous birds, such as mergansers and loons, a change in feeding ecology of S. trutta or changes in population densities of copepods, fish or birds might have influenced the infection pattern. No relationships between D. ditremum infection and muscle-tissue δ 15 N signature or Hg concentration were found, indicating that infection is not a result of piscivory or cannibalism. Furthermore, consumption of copepods by S. trutta during summer and autumn was low. On the other hand, the number of piscivorous birds has increased, probably due to the presence of P. phoxinus as a new and numerous prey. An increased number of final D. ditremum hosts may have produced a higher output of cestode eggs, resulting in more infected copepods that in turn are consumed by S. trutta. Indirectly, P. phoxinus may therefore have caused the observed increased infection in S. trutta and thereby imposed further negative effects on S. trutta in high mountain areas. © 2017 The Fisheries Society of the British Isles.

  4. A Novel Murine Model of Established Staphylococcal Bone Infection in the Presence of a Fracture Fixation Plate to Study Therapies Utilizing Antibiotic-laden Spacers after Revision Surgery

    Science.gov (United States)

    Inzana, Jason A.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

    2014-01-01

    Mice are the small animal model of choice in biomedical research due to the low cost and availability of genetically engineered lines. However, the devices utilized in current mouse models of implant-associated bone infection have been limited to intramedullary or trans-cortical pins, which are not amenable to treatments involving extensive debridement of a full-thickness bone loss and placement of a segmental antibiotic spacer. To overcome these limitations, we developed a clinically faithful model that utilizes a locking fracture fixation plate to enable debridement of an infected segmental bone defect (full-thickness osteotomy) during a revision surgery, and investigated the therapeutic effects of placing an antibiotic-laden spacer in the segmental bone defect. To first determine the ideal time point for revision following infection, a 0.7 mm osteotomy in the femoral mid-shaft was stabilized with a radiolucent PEEK fixation plate. The defect was inoculated with bioluminescent Staphylococcus aureus, and the infection was monitored over 14 days by bioluminescent imaging (BLI). Osteolysis and reactive bone formation were assessed by X-ray and micro-computed tomography (micro-CT). The active bacterial infection peaked by 5 days post-inoculation, however the stability of the implant fixation became compromised by 10–14 days post-inoculation due to osteolysis around the screws. Thus, day 7 was defined as the ideal time point to perform the revision surgery. During the revision surgery, the infected tissue was debrided and the osteotomy was widened to 3 mm to place a poly-methyl methacrylate spacer, with or without vancomycin. Half of the groups also received systemic vancomycin for the remaining 21 days of the study. The viable bacteria remaining at the end of the study were measured using colony forming unit assays. Volumetric bone changes (osteolysis and reactive bone formation) were directly measured using micro-CT image analysis. Mice that were treated with

  5. Towards an HIV-1 cure: measuring the latent reservoir.

    Science.gov (United States)

    Bruner, Katherine M; Hosmane, Nina N; Siliciano, Robert F

    2015-04-01

    The latent reservoir (LR) of HIV-1 in resting memory CD4(+) T cells serves as a major barrier to curing HIV-1 infection. While many PCR- and culture-based assays have been used to measure the size of the LR, correlation between results of different assays is poor and recent studies indicate that no available assay provides an accurate measurement of reservoir size. The discrepancies between assays are a hurdle to clinical trials that aim to measure the efficacy of HIV-1 eradication strategies. Here we describe the advantages and disadvantages of various approaches to measuring the LR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The Latent Class Model as a Measurement Model for Situational Judgment Tests

    Directory of Open Access Journals (Sweden)

    Frank Rijmen

    2011-11-01

    Full Text Available In a situational judgment test, it is often debatable what constitutes a correct answer to a situation. There is currently a multitude of scoring procedures. Establishing a measurement model can guide the selection of a scoring rule. It is argued that the latent class model is a good candidate for a measurement model. Two latent class models are applied to the Managing Emotions subtest of the Mayer, Salovey, Caruso Emotional Intelligence Test: a plain-vanilla latent class model, and a second-order latent class model that takes into account the clustering of several possible reactions within each hypothetical scenario of the situational judgment test. The results for both models indicated that there were three subgroups characterised by the degree to which differentiation occurred between possible reactions in terms of perceived effectiveness. Furthermore, the results for the second-order model indicated a moderate cluster effect.

  7. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

    NARCIS (Netherlands)

    Lee, Laurel Yong-Hwa; Anh, Ha Do Lien; Simmons, Cameron; de Jong, Menno D.; Chau, Nguyen Van Vinh; Schumacher, Reto; Peng, Yan Chun; McMichael, Andrew J.; Farrar, Jeremy J.; Smith, Geoffrey L.; Townsend, Alain R. M.; Askonas, Brigitte A.; Rowland-Jones, Sarah; Dong, Tao

    2008-01-01

    The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to

  8. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

    DEFF Research Database (Denmark)

    Krishna, B A; Spiess, K; Poole, E L

    2017-01-01

    Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV ...

  9. Histone deacetylase inhibitors for purging HIV-1 from the latent reservoir.

    NARCIS (Netherlands)

    Matalon, S.; Rasmussen, T.A.; Dinarello, C.A.

    2011-01-01

    A reservoir of latently infected memory CD4(+) T cells is believed to be the source of HIV-1 reemergence after discontinuation of antiretroviral therapy. HIV-1 eradication may depend on depletion of this reservoir. Integrated HIV-1 is inaccessible for expression, in part because of histone

  10. Establishing a successful HIV counseling and testing service. A blueprint for preventing pediatric HIV infections and translating research into clinical practice.

    Science.gov (United States)

    Rips, J

    1997-12-01

    The findings of ACTG 076 have already resulted in local, state, and federal legislative initiatives targeted at pregnant and post-partum women and their newborns. This article advises clinicians and administrations on setting up successful voluntary prenatal HIV counseling and testing programs for early detection of HIV infection, and complying with the burgeoning array of legislative directives. Over the past several years their have been attempts to optimize and evaluate testing programs--perinatal ZDV counseling and administration of ZDV--and to link HIV-infected women with care in academic, community, and municipal hospitals. The suggestions are, therefore, broad enough to be applicable to a full array of clinical practices, from a private single provider office to a large hospital-based prenatal clinic. It is hoped that the models presented in this article can be replicated in diverse settings, and that readers can avoid the pitfalls and barriers sometimes encountered.

  11. Latent lifestyle preferences and household location decisions

    Science.gov (United States)

    Walker, Joan L.; Li, Jieping

    2007-04-01

    Lifestyle, indicating preferences towards a particular way of living, is a key driver of the decision of where to live. We employ latent class choice models to represent this behavior, where the latent classes are the lifestyles and the choice model is the choice of residential location. Thus, we simultaneously estimate lifestyle groups and how lifestyle impacts location decisions. Empirical results indicate three latent lifestyle segments: suburban dwellers, urban dwellers, and transit-riders. The suggested lifestyle segments have intriguing policy implications. Lifecycle characteristics are used to predict lifestyle preferences, although there remain significant aspects that cannot be explained by observable variables.

  12. Extraction of latent images from printed media

    Science.gov (United States)

    Sergeyev, Vladislav; Fedoseev, Victor

    2015-12-01

    In this paper we propose an automatic technology for extraction of latent images from printed media such as documents, banknotes, financial securities, etc. This technology includes image processing by adaptively constructed Gabor filter bank for obtaining feature images, as well as subsequent stages of feature selection, grouping and multicomponent segmentation. The main advantage of the proposed technique is versatility: it allows to extract latent images made by different texture variations. Experimental results showing performance of the method over another known system for latent image extraction are given.

  13. Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection

    DEFF Research Database (Denmark)

    Bélard, Erika; Semb, Synne; Ruhwald, Morten

    2011-01-01

    (TST). METHODS: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44). RESULTS: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54....../238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had =1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone.......0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P negative effect was found for long...

  14. Bayesian Latent Class Analysis Tutorial.

    Science.gov (United States)

    Li, Yuelin; Lord-Bessen, Jennifer; Shiyko, Mariya; Loeb, Rebecca

    2018-01-01

    This article is a how-to guide on Bayesian computation using Gibbs sampling, demonstrated in the context of Latent Class Analysis (LCA). It is written for students in quantitative psychology or related fields who have a working knowledge of Bayes Theorem and conditional probability and have experience in writing computer programs in the statistical language R . The overall goals are to provide an accessible and self-contained tutorial, along with a practical computation tool. We begin with how Bayesian computation is typically described in academic articles. Technical difficulties are addressed by a hypothetical, worked-out example. We show how Bayesian computation can be broken down into a series of simpler calculations, which can then be assembled together to complete a computationally more complex model. The details are described much more explicitly than what is typically available in elementary introductions to Bayesian modeling so that readers are not overwhelmed by the mathematics. Moreover, the provided computer program shows how Bayesian LCA can be implemented with relative ease. The computer program is then applied in a large, real-world data set and explained line-by-line. We outline the general steps in how to extend these considerations to other methodological applications. We conclude with suggestions for further readings.

  15. Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir

    OpenAIRE

    Wang, Zheng; Simonetti, Francesco R.; Siliciano, Robert F.; Laird, Gregory M.

    2018-01-01

    Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as it consists of a mosaic population of defective and intact proviruses that can shift from a state of latency to active HIV-1 transcription. Due to this complexity, most of the current assays detect multiple categories of persistent HIV-1, leading to an overestimate of the true size of th...

  16. [Quantitative assessment of fungal risk in the case of construction works in healthcare establishments: Proposed indicators for the determination of the impact of management precautions on the risk of fungal infection].

    Science.gov (United States)

    Gangneux, J-P; Adjidé, C-C; Bernard, L; Botterel, F; Carel, A; Castel, O; Derouin, F; Hoarau, G; Labussière, H; Lafaurie, M; Millon, L; Pottecher, B; Thiebaut, A; Turco, M; Baron, R

    2012-03-01

    Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used. Copyright © 2012. Published by Elsevier SAS.

  17. Prevalence of large endoparasites at necropsy in horses infected with Population B small strongyles in a herd established in Kentucky in 1966.

    Science.gov (United States)

    Lyons, E T; Tolliver, S C; Collins, S S

    2006-07-01

    Two closed horse herds (Old Lot 4 and Field 24), infected since 1966 with Population B small strongyles resistant to thiabendazole (TBZ) and phenothiazine (PTZ), were terminated in February, March, and May, 2005. At necropsy, only the large endoparasites were identified and counted. The number of horses on pasture was 14 (239 days of age to 23 years old) for Old Lot 4 and two (3 to 20 years old) for Field 24. The time of the last antiparasitic treatment, relative to the year (2005) of necropsy, was 26 years for Old Lot 4 and 9 years for Field 24 horses. Gasterophilus intestinalis third instars (three to 113 specimens/horse) were found in all 16 horses and second instars (one to two) in two horses. Gasterophilus nasalis third instars (one to three) were recovered from five horses. Parascaris equorum infections (23 to 144) were in four horses (239 days to 4 years old). Strongylus vulgaris were present in the large intestine (one to 155) of 13 horses from 239 days to 23 years old and in the cranial mesenteric artery (two to 79) in 10 horses from 239 days to 23 years old. Strongylus edentatus were in the large intestine (two to 101) of 12 horses, ranging in age from 2.5 to 23 years old and in the ventral abdominal wall (one to 53) of six horses from 239 days to 21 years old. Specimens (seven to 872) of Anoplocephala perfoliata were in all horses. Oxyuris equi (one to 129) were recovered from seven horses (330 days to 23 years old). Thelazia lacrymalis (one to 85) infected the eyes of five horses (317 days to 11 years old).

  18. Heteroscedastic Latent Trait Models for Dichotomous Data.

    Science.gov (United States)

    Molenaar, Dylan

    2015-09-01

    Effort has been devoted to account for heteroscedasticity with respect to observed or latent moderator variables in item or test scores. For instance, in the multi-group generalized linear latent trait model, it could be tested whether the observed (polychoric) covariance matrix differs across the levels of an observed moderator variable. In the case that heteroscedasticity arises across the latent trait itself, existing models commonly distinguish between heteroscedastic residuals and a skewed trait distribution. These models have valuable applications in intelligence, personality and psychopathology research. However, existing approaches are only limited to continuous and polytomous data, while dichotomous data are common in intelligence and psychopathology research. Therefore, in present paper, a heteroscedastic latent trait model is presented for dichotomous data. The model is studied in a simulation study, and applied to data pertaining alcohol use and cognitive ability.

  19. Latent Heat Storage Through Phase Change Materials

    Indian Academy of Sciences (India)

    IAS Admin

    reducing storage volume for different materials. The examples are numerous: ... Latent heat is an attractive way to store solar heat as it provides high energy storage density, .... Maintenance of the PCM treated fabric is easy. The melted PCM.

  20. Failure of PCR to Detect Treponema pallidum ssp. pertenue DNA in Blood in Latent Yaws.

    Directory of Open Access Journals (Sweden)

    Michael Marks

    Full Text Available Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA and Rapid Plasma Reagin (RPR tests and 7 controls (negative serology, all collected as part of a prospective study of yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active yaws whilst 128 were considered to have latent yaws. 43 children had high titre rapid plasma reagins (RPRs of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in yaws than in syphilis. As the goal of the yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool.

  1. Failure of PCR to Detect Treponema pallidum ssp. pertenue DNA in Blood in Latent Yaws.

    Science.gov (United States)

    Marks, Michael; Katz, Samantha; Chi, Kai-Hua; Vahi, Ventis; Sun, Yongcheng; Mabey, David C; Solomon, Anthony W; Chen, Cheng Y; Pillay, Allan

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA) and Rapid Plasma Reagin (RPR) tests and 7 controls (negative serology), all collected as part of a prospective study of yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active yaws whilst 128 were considered to have latent yaws. 43 children had high titre rapid plasma reagins (RPRs) of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in yaws than in syphilis. As the goal of the yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool.

  2. Latent variables and route choice behavior

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo; Bekhor, Shlomo; Pronello, Cristina

    2012-01-01

    In the last decade, a broad array of disciplines has shown a general interest in enhancing discrete choice models by considering the incorporation of psychological factors affecting decision making. This paper provides insight into the comprehension of the determinants of route choice behavior...... and bound algorithm. A hybrid model consists of measurement equations, which relate latent variables to measurement indicators and utilities to choice indicators, and structural equations, which link travelers’ observable characteristics to latent variables and explanatory variables to utilities. Estimation...

  3. UNSOLVED AND LATENT CRIME: DIFFERENCES AND SIMILARITIES

    Directory of Open Access Journals (Sweden)

    Mikhail Kleymenov

    2017-01-01

    Full Text Available УДК 343Purpose of the article is to study the specific legal and informational nature of the unsolved crime in comparison with the phenomenon of delinquency, special study and analysis to improve the efficiency of law enforcement.Methods of research are abstract-logical, systematic, statistical, study of documents. The main results of research. Unsolved crime has specific legal, statistical and informational na-ture as the crime phenomenon, which is expressed in cumulative statistical population of unsolved crimes. An array of unsolved crimes is the sum of the number of acts, things of which is suspended and not terminated. The fault of the perpetrator in these cases is not proven, they are not considered by the court, it is not a conviction. Unsolved crime must be registered. Latent crime has a different informational nature. The main symptom of latent crimes is the uncertainty for the subjects of law enforcement, which delegated functions of identification, registration and accounting. Latent crime is not recorded. At the same time, there is a "border" area between the latent and unsolved crimes, which includes covered from the account of the crime. In modern Russia the majority of crimes covered from accounting by passing the decision about refusal in excitation of criminal case. Unsolved crime on their criminogenic consequences represents a significant danger to the public is higher compared to latent crime.It is conducted in the article a special analysis of the differences and similarities in the unsolved latent crime for the first time in criminological literature.The analysis proves the need for radical changes in the current Russian assessment of the state of crime and law enforcement to solve crimes. The article argues that an unsolved crime is a separate and, in contrast to latent crime, poorly understood phenomenon. However unsolved latent crime and have common features and areas of interaction.

  4. Exposing Latent Information in Folksonomies for Reasoning

    Science.gov (United States)

    2010-01-14

    1.73 $.") http://www.w3.org/2006/07/SWD/ SKOS /reference/20081001/ Spiteri, L.F. (2007) "The structure and form of folksonomy tags: The road to the...Exposing Latent Information in Folksonomies for Reasoning January 14, 2010 Sponsored by Defense Advanced Research Projects Agency (DOD...DATES COVERED (From - To! 4/14/2009-12/23/2009 4. TITLE AND SUBTITLE Exposing Latent Information in Folksonomies for Reasoning Sa. CONTRACT

  5. Handbook of latent variable and related models

    CERN Document Server

    Lee, Sik-Yum

    2011-01-01

    This Handbook covers latent variable models, which are a flexible class of models for modeling multivariate data to explore relationships among observed and latent variables.- Covers a wide class of important models- Models and statistical methods described provide tools for analyzing a wide spectrum of complicated data- Includes illustrative examples with real data sets from business, education, medicine, public health and sociology.- Demonstrates the use of a wide variety of statistical, computational, and mathematical techniques.

  6. Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection.

    Science.gov (United States)

    Ma, Y; Gregorio, G; Gäken, J; Muratori, L; Bianchi, F B; Mieli-Vergani, G; Vergani, D

    1997-06-01

    Liver kidney microsomal type 1 antibody (LKM1) is the diagnostic marker of autoimmune hepatitis (AIH) type 2 and is also found in patients with hepatitis C virus (HCV) infection. Cytochrome P4502D6 (CYP2D6) is the documented target antigen of LKM1 in AIH, but not in HCV infection. To compare the reactivity in the two conditions, we established a radioligand assay using eukaryotically expressed CYP2D6 as target. A 1.2-kb human CYP2D6 cDNA was isolated from a human liver cDNA library and subcloned into an in vitro transcription vector pSP64 Poly(A). Recombinant CYP2D6 was then produced by in vitro transcription/translation, metabolically labelled with 35S methionine and used in the immunoprecipitation assay. Antibodies that bound radiolabelled CYP2D6 were immunoprecipitated and their levels assessed as cpm. Sera from 50 LKM1-positive patients (26 with AIH; 24 with HCV infection), 128 LKM1-negative patients and 57 normal controls were tested. Reactivity to 35S labelled CYP2D6 was observed in all LKM1-positive sera from patients with AIH and HCV infection, but in none of the controls. The cpm in both conditions were significantly higher than in normal controls (pLKM1 (r 0.87, p<0.001 and r=0.64, p<0.001 for AIH and HCV infection, respectively). Reactivity to 35S labelled CYP2D6 was inhibited by addition of an excess of eukaryotically expressed CYP2D6. CYP2D6 is a major target antigen of both AIH and HCV infection. The novel radioligand assay is highly sensitive and specific.

  7. Scintigraphy in detection of latent inflammatory foci in patients with pseudarthroses

    International Nuclear Information System (INIS)

    Woy-Wojciechowski, J.; Zawadzinski, S.

    1982-01-01

    Treatment of infected pseudarthroses is one of the most difficult problems in orthopaedic surgery. Presence of latent inflammatory foci may be a serious complication after bone grafting. In 14 cases of pseudarthroses radioisotope scanning demonstrated in 5 cases presence of additional latent inflammatory foci which gave cues as to the type and extent of surgical treatment. In all these cases evaluation of the local condition by X-ray examination was insufficient. Isotope scanning was useful for a radical surgical treatment making possible complete eradication of the inflammation and reducing thus the risk of inflammation recurrence at the site of the operation performed for achieving bone union or for implanting bone graft. (author)

  8. The Latent Structure of Dictionaries.

    Science.gov (United States)

    Vincent-Lamarre, Philippe; Massé, Alexandre Blondin; Lopes, Marcos; Lord, Mélanie; Marcotte, Odile; Harnad, Stevan

    2016-07-01

    How many words-and which ones-are sufficient to define all other words? When dictionaries are analyzed as directed graphs with links from defining words to defined words, they reveal a latent structure. Recursively removing all words that are reachable by definition but that do not define any further words reduces the dictionary to a Kernel of about 10% of its size. This is still not the smallest number of words that can define all the rest. About 75% of the Kernel turns out to be its Core, a "Strongly Connected Subset" of words with a definitional path to and from any pair of its words and no word's definition depending on a word outside the set. But the Core cannot define all the rest of the dictionary. The 25% of the Kernel surrounding the Core consists of small strongly connected subsets of words: the Satellites. The size of the smallest set of words that can define all the rest-the graph's "minimum feedback vertex set" or MinSet-is about 1% of the dictionary, about 15% of the Kernel, and part-Core/part-Satellite. But every dictionary has a huge number of MinSets. The Core words are learned earlier, more frequent, and less concrete than the Satellites, which are in turn learned earlier, more frequent, but more concrete than the rest of the Dictionary. In principle, only one MinSet's words would need to be grounded through the sensorimotor capacity to recognize and categorize their referents. In a dual-code sensorimotor/symbolic model of the mental lexicon, the symbolic code could do all the rest through recombinatory definition. Copyright © 2016 Cognitive Science Society, Inc.

  9. Latent-Trait Latent-Class Analysis of Self-disclosure in the Work Environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  10. Latent-trait latent-class analysis of selfdisclosure in the work environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2006-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  11. Latent-Trait Latent-Class Analysis of Self-Disclosure in the Work Environment

    Science.gov (United States)

    Maij-de Meij, Annette M.; Kelderman, Henk; van der Flier, Henk

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of self-disclosure. The model was used to analyze the data…

  12. Latent-trait latent-class analysis of selfdisclosure in the work environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  13. Establishment of reverse transcription loop-mediated isothermal amplification for rapid detection and differentiation of canine distemper virus infected and vaccinated animals.

    Science.gov (United States)

    Liu, Da-Fei; Liu, Chun-Guo; Tian, Jin; Jiang, Yi-Tong; Zhang, Xiao-Zhan; Chai, Hong-Liang; Yang, Tian-Kuo; Yin, Xiu-Chen; Zhang, Hong-Ying; Liu, Ming; Hua, Yu-Ping; Qu, Lian-Dong

    2015-06-01

    Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers-two internal and two external-were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water bath held at a constant temperature of 65°C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10(-1)TCID50ml(-1). The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Abalone viral ganglioneuritis: establishment and use of an experimental immersion challenge system for the study of abalone herpes virus infections in Australian abalone.

    Science.gov (United States)

    Corbeil, Serge; McColl, Kenneth A; Williams, Lynette M; Mohammad, Ilhan; Hyatt, Alexander D; Crameri, Sandra G; Fegan, Mark; Crane, Mark St J

    2012-05-01

    In late 2005, acute mortalities occurred in abalone on farms located in Victoria, Australia. Disease was associated with infection by an abalone herpes virus (AbHV). Subsequently, starting in 2006, the disease (abalone viral ganglioneuritis; AVG) was discovered in wild abalone in Victorian open waters. Currently, it continues to spread, albeit at a slow rate, along the Victorian coast-line. Here, we report on experimental transmission trials that were carried out by immersion using water into which diseased abalone had shed infectious viral particles. At various time points following exposure, naïve abalone were assessed by an AbHV-specific real-time PCR and histological analyses including in situ hybridization (ISH). Results demonstrated that while exposed abalone began displaying clinical signs of the disease from 60 hours post exposure (hpe), they tested positive for the presence of viral DNA at 36 hpe. Of further interest, the AbHV DNA probe used in the ISH assay detected the virus as early as 48 hpe. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  15. Reactivation of Latent Epstein-Barr Virus; A Comparison After Gamma Rays and Proton Treatment

    Science.gov (United States)

    Mehta, Satish K.; Plante, Ianik; Bloom, David C.; Stowe, Raymond; Renner, Ashlie; Wu, Honglu; Crucian, Brian; Pierson, Duane L.

    2017-01-01

    Among different unique stressors astronauts are exposed to during spaceflight, cosmic radiation constitutes an important one that leads to various health effects. In particular, space radiation may contribute to decreased immunity, which has been observed in astronauts during short and long duration missions, as evidenced by several changes in cellular immunity and plasma cytokines levels. Reactivation of latent herpes viruses, either directly from radiation or resulting from perturbation in the immune system, is also observed in astronauts. While EBV is one of the eight human herpes viruses known to infect more than 90% human adults and stays latent for the life of the host without normally causing adverse effects of reactivation, increased reactivation in astronauts is well-documented, though the mechanism of this increase is not understood. In this work, we have studied the effect of two different types of radiations, Cs-137 gamma and 150-MeV proton on the reactivation rates of the Epstein - Barr virus (EBV) in vitro in EBV latent cell lines at doses of 0.1, 0.5, 1.0 and 2.0 Gy. While we find that both types of radiations reactivated latent EBV in vitro, we observe that at equivalent doses, early response is stronger for protons but with time, the reactivation induced by gamma rays is more persistent. These differences between the protons and gamma rays curves in latent virus reactivation challenge the common paradigm that protons and gamma rays have similar biological effects.

  16. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis.

    Science.gov (United States)

    Clifford, Vanessa; Tebruegge, Marc; Zufferey, Christel; Germano, Susie; Forbes, Ben; Cosentino, Lucy; McBryde, Emma; Eisen, Damon; Robins-Browne, Roy; Street, Alan; Denholm, Justin; Curtis, Nigel

    2017-08-01

    A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. Latent Tuberculosis in Pregnancy: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Isabelle Malhamé

    Full Text Available In countries with low tuberculosis (TB incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI. The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial.In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection.A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1 Full text was not available (2 they were case series or case studies (3 they focused exclusively on prevalence, diagnosis and treatment of active TB (4 the study population was exclusively HIV-infected.Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07. There was a high level of adherence with both skin testing (between 90-100% and chest radiography (93-100%.. In three studies from low incidence settings, concordance between TST and an interferon

  18. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate.

    OpenAIRE

    Coen, D M; Kosz-Vnenchak, M; Jacobson, J G; Leib, D A; Bogard, C L; Schaffer, P A; Tyler, K L; Knipe, D M

    1989-01-01

    Herpes simplex virus infection of mammalian hosts involves lytic replication at a primary site, such as the cornea, translocation by axonal transport to sensory ganglia and replication, and latent infection at a secondary site, ganglionic neurons. The virus-encoded thymidine kinase, which is a target for antiviral drugs such as acyclovir, is not essential for lytic replication yet evidently is required at the secondary site for replication and some phase of latent infection. To determine the ...

  19. Latent Growth and Dynamic Structural Equation Models.

    Science.gov (United States)

    Grimm, Kevin J; Ram, Nilam

    2018-05-07

    Latent growth models make up a class of methods to study within-person change-how it progresses, how it differs across individuals, what are its determinants, and what are its consequences. Latent growth methods have been applied in many domains to examine average and differential responses to interventions and treatments. In this review, we introduce the growth modeling approach to studying change by presenting different models of change and interpretations of their model parameters. We then apply these methods to examining sex differences in the development of binge drinking behavior through adolescence and into adulthood. Advances in growth modeling methods are then discussed and include inherently nonlinear growth models, derivative specification of growth models, and latent change score models to study stochastic change processes. We conclude with relevant design issues of longitudinal studies and considerations for the analysis of longitudinal data.

  20. Learning Latent Structure in Complex Networks

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai

    such as the Modularity, it has recently been shown that latent structure in complex networks is learnable by Bayesian generative link distribution models (Airoldi et al., 2008, Hofman and Wiggins, 2008). In this paper we propose a new generative model that allows representation of latent community structure......Latent structure in complex networks, e.g., in the form of community structure, can help understand network dynamics, identify heterogeneities in network properties, and predict ‘missing’ links. While most community detection algorithms are based on optimizing heuristic clustering objectives...... as in the previous Bayesian approaches and in addition allows learning of node specific link properties similar to that in the modularity objective. We employ a new relaxation method for efficient inference in these generative models that allows us to learn the behavior of very large networks. We compare the link...

  1. Latent Microsporidial Infection in Immunocompetent Individuals – A Longitudinal Study

    Czech Academy of Sciences Publication Activity Database

    Sak, Bohumil; Kváč, Martin; Kučerová, Z.; Květoňová, Dana; Saková, Kamila

    2011-01-01

    Roč. 5, č. 5 (2011), e1162 ISSN 1935-2735 R&D Projects: GA AV ČR KJB500960701; GA ČR GP523/07/P117 Institutional research plan: CEZ:AV0Z60220518 Keywords : Microsporidia * AIDS * indirect immunofluorescence assay * Encephalitozoon * immunosupression Subject RIV: EC - Immunology Impact factor: 4.716, year: 2011

  2. Treatment: Latent TB Infection (LTBI) and TB Disease

    Science.gov (United States)

    ... Adverse Events TB Treatment of Persons Living with HIV TB Treatment and Pregnancy TB Treatment for Children Drug-Resistant TB Research TB Epidemiologic Studies Consortium Research Projects Publications TB Trials Consortium Study ...

  3. Detection of latent infection by Ralstonia solanacearum in potato ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... solanacearum in potato tuber seed certification schemes more so in screening for presence of R. solanacearum in seed ... Bacterial wilt is, after late blight, the most important ... with respect to tuber-borne diseases such as bacterial wilt and those ... The potato crop was preceded by maize. Bacterial wilt ...

  4. A Multinomial Probit Model with Latent Factors

    DEFF Research Database (Denmark)

    Piatek, Rémi; Gensowski, Miriam

    2017-01-01

    be meaningfully linked to an economic model. We provide sufficient conditions that make this structure identified and interpretable. For inference, we design a Markov chain Monte Carlo sampler based on marginal data augmentation. A simulation exercise shows the good numerical performance of our sampler......We develop a parametrization of the multinomial probit model that yields greater insight into the underlying decision-making process, by decomposing the error terms of the utilities into latent factors and noise. The latent factors are identified without a measurement system, and they can...

  5. Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

    Science.gov (United States)

    Choudhury, Vivek; Amin, Sanjiv B; Agarwal, Asha; Srivastava, L M; Soni, Arun; Saluja, Satish

    2015-11-01

    In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score 75 ng/mL) at birth. Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397. © 2015 American Society for Nutrition.

  6. PROBLEM OF OPTIMAL CONTROL OF EPIDEMIC IN VIEW OF LATENT PERIOD

    Directory of Open Access Journals (Sweden)

    2017-01-01

    Full Text Available The problem of optimal control of epidemic through vaccination and isolation, taking into account latent period is considered. The target function is minimized - functionality summarizing costs on epidemic prevention and treatment and also considering expenses on infected people left at the end of control T who may be a new source of epidemic. On the left endpoint of the integration segment initial data is given - quantity of infected and confirmed people at the moment t, the right endpoint is free. The dynamic constraints are written by way of a system of simple differential equations describing the speed of changes of number of subjected to infection and number of already infected. Besides the inhomogeneous communi- ty is considered, consisting of four age groups (babies, preschool children, school children and adults. The speed of vaccina- tion (number of vaccinated per a time unit and isolation speed are used as the control functions. There are some restrictions on control above and below. The latent period is described by the constant h and is part of the equation describing the con- tamination speed of people as a retarding in argument t, i.e. a person being in a latent period infects others not being aware of his disease. For problem solving Pontryagin maximum principle is used where it can be seen that the control is piecewise constant. The result of numerical implementation of discrete problem of optimal control is given. The conclusions are made that the latent period significantly influence the incidence rate and as consequence the costs on epidemic suppression. The programme based on the programming language Delphi gives an opportunity to estimate the scale of epidemic at different initial data and restrictions on control as well as to find an optimal control minimizing costs on epimedic suppression.

  7. A probabilistic transmission and population dynamic model to assess tuberculosis infection risk.

    Science.gov (United States)

    Liao, Chung-Min; Cheng, Yi-Hsien; Lin, Yi-Jun; Hsieh, Nan-Hung; Huang, Tang-Luen; Chio, Chia-Pin; Chen, Szu-Chieh; Ling, Min-Pei

    2012-08-01

    The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R₀) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R₀ estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality. © 2012 Society for Risk Analysis.

  8. Tratamento da tuberculose de infecção latente. As recomendações actuais

    Directory of Open Access Journals (Sweden)

    R. Duarte

    2010-09-01

    Full Text Available Resumo: O diagnóstico e tratamento da infecção latente por Mycobacterium tuberculosis reduz significativamente o risco de desenvolvimento de tuberculose activa e a transmissão da doença na comunidade. O rastreio da tuberculose infecção latente deve passar pela exclusão de doença activa (inquérito de sintomas e radiografia pulmonar e avaliação da resposta imunológica ao M. tuberculosis através dos testes actualmente ao dispor, como o teste tuberculínico e os testes IGRA (interferon-gamma release assay. A escolha do esquema de tratamento deve ter em linha de conta a eficácia, a adesão e os efeitos colaterais associados ao mesmo Este documento actualiza as recomendações sobre tratamento da tuberculose infecção latente. São apresentadas indicações sobre quem deve ser rastreado e revistos os esquemas de tratamento. Abstract: Diagnosis and treatment of latent infection with Mycobacterium tuberculosis (LTBI, significantly reduces the risk of developing active tuberculosis and the transmission of the disease in the community. LTBI screening must pass by the exclusion of active disease (symptoms enquiry and chest radiography and assessment of immune response to Mycobacterium tuberculosis testing with the tests currently available – tuberculin skin test and interferon-gamma release assay (IGRA. The choice of treatment must take into account the efficacy and side effects associated with the same. This document provides updated recommendations on latent tuberculosis infection treatment. Topics covered include whom to test for TB and reviewed LTBI treatment regimens. Palavras-chave: Tuberculose, tuberculose infeccao latente, tratamento, preventivo, Key words: Tuberculosis, latent tuberculosis infection, treatment, preventive

  9. Latent human error analysis and efficient improvement strategies by fuzzy TOPSIS in aviation maintenance tasks.

    Science.gov (United States)

    Chiu, Ming-Chuan; Hsieh, Min-Chih

    2016-05-01

    The purposes of this study were to develop a latent human error analysis process, to explore the factors of latent human error in aviation maintenance tasks, and to provide an efficient improvement strategy for addressing those errors. First, we used HFACS and RCA to define the error factors related to aviation maintenance tasks. Fuzzy TOPSIS with four criteria was applied to evaluate the error factors. Results show that 1) adverse physiological states, 2) physical/mental limitations, and 3) coordination, communication, and planning are the factors related to airline maintenance tasks that could be addressed easily and efficiently. This research establishes a new analytic process for investigating latent human error and provides a strategy for analyzing human error using fuzzy TOPSIS. Our analysis process complements shortages in existing methodologies by incorporating improvement efficiency, and it enhances the depth and broadness of human error analysis methodology. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Risk for latent and active tuberculosis in Germany.

    Science.gov (United States)

    Herzmann, Christian; Sotgiu, Giovanni; Bellinger, Oswald; Diel, Roland; Gerdes, Silke; Goetsch, Udo; Heykes-Uden, Helga; Schaberg, Tom; Lange, Christoph

    2017-06-01

    Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

  11. Variable importance in latent variable regression models

    NARCIS (Netherlands)

    Kvalheim, O.M.; Arneberg, R.; Bleie, O.; Rajalahti, T.; Smilde, A.K.; Westerhuis, J.A.

    2014-01-01

    The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable

  12. Detection of latent prints by Raman imaging

    Science.gov (United States)

    Lewis, Linda Anne [Andersonville, TN; Connatser, Raynella Magdalene [Knoxville, TN; Lewis, Sr., Samuel Arthur

    2011-01-11

    The present invention relates to a method for detecting a print on a surface, the method comprising: (a) contacting the print with a Raman surface-enhancing agent to produce a Raman-enhanced print; and (b) detecting the Raman-enhanced print using a Raman spectroscopic method. The invention is particularly directed to the imaging of latent fingerprints.

  13. Statistical inference based on latent ability estimates

    NARCIS (Netherlands)

    Hoijtink, H.J.A.; Boomsma, A.

    The quality of approximations to first and second order moments (e.g., statistics like means, variances, regression coefficients) based on latent ability estimates is being discussed. The ability estimates are obtained using either the Rasch, oi the two-parameter logistic model. Straightforward use

  14. Residual Structures in Latent Growth Curve Modeling

    Science.gov (United States)

    Grimm, Kevin J.; Widaman, Keith F.

    2010-01-01

    Several alternatives are available for specifying the residual structure in latent growth curve modeling. Two specifications involve uncorrelated residuals and represent the most commonly used residual structures. The first, building on repeated measures analysis of variance and common specifications in multilevel models, forces residual variances…

  15. Forensic Chemistry: The Revelation of Latent Fingerprints

    Science.gov (United States)

    Friesen, J. Brent

    2015-01-01

    The visualization of latent fingerprints often involves the use of a chemical substance that creates a contrast between the fingerprint residues and the surface on which the print was deposited. The chemical-aided visualization techniques can be divided into two main categories: those that chemically react with the fingerprint residue and those…

  16. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

    2015-01-01

    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chr...

  17. Incorporating direct marketing activity into latent attrition models

    NARCIS (Netherlands)

    Schweidel, David A.; Knox, George

    2013-01-01

    When defection is unobserved, latent attrition models provide useful insights about customer behavior and accurate forecasts of customer value. Yet extant models ignore direct marketing efforts. Response models incorporate the effects of direct marketing, but because they ignore latent attrition,

  18. Generalized latent variable modeling multilevel, longitudinal, and structural equation models

    CERN Document Server

    Skrondal, Anders; Rabe-Hesketh, Sophia

    2004-01-01

    This book unifies and extends latent variable models, including multilevel or generalized linear mixed models, longitudinal or panel models, item response or factor models, latent class or finite mixture models, and structural equation models.

  19. Space Flight-Induced Reactivation of Latent Epstein-Barr Virus

    Science.gov (United States)

    Stowe, Raymond P.; Barrett, Alan D. T.; Pierson, Duane L.

    2001-01-01

    Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. We hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B-lymphocytes. If increased virus production and clonal expansion of infected B-lymphocytes are detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease. More importantly, we will begin to understand the basic mechanisms involved in stress-induced reactivation of EBV in circulating B-lymphocytes.

  20. Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir.

    Science.gov (United States)

    Wang, Zheng; Simonetti, Francesco R; Siliciano, Robert F; Laird, Gregory M

    2018-02-13

    Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as it consists of a mosaic population of defective and intact proviruses that can shift from a state of latency to active HIV-1 transcription. Due to this complexity, most of the current assays detect multiple categories of persistent HIV-1, leading to an overestimate of the true size of the latent reservoir. Here, we review the development of the viral outgrowth assay, the gold-standard quantification of replication-competent proviruses, and discuss the insights provided by full-length HIV-1 genome sequencing methods, which allowed us to unravel the composition of the proviral landscape. In this review, we provide a dissection of what defines HIV-1 persistence and we examine the unmet needs to measure the efficacy of interventions aimed at eliminating the HIV-1 reservoir.

  1. Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the Cytoskeleton

    Science.gov (United States)

    2018-01-01

    Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has the ability to infect and replicate within epithelial cells and neurons and establish a life-long latent infection in sensory neurons. HSV-1 depends on the host cellular cytoskeleton for entry, replication, and exit. Therefore, HSV-1 has adapted mechanisms to promote its survival by exploiting the microtubule and actin cytoskeletons to direct its active transport, infection, and spread between neurons and epithelial cells during primary and recurrent infections. This review will focus on the currently known mechanisms utilized by HSV-1 to harness the neuronal cytoskeleton, molecular motors, and the secretory and exocytic pathways for efficient virus entry, axonal transport, replication, assembly, and exit from the distinct functional compartments (cell body and axon) of the highly polarized sensory neurons. PMID:29473915

  2. Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.

    Science.gov (United States)

    Lee, Hyoin; Jung, Seungmoon; Lee, Peter; Jeong, Yong

    2017-10-01

    The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during

  3. Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV.

    Science.gov (United States)

    Kim, Youry; Anderson, Jenny L; Lewin, Sharon R

    2018-01-10

    Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival. Here, we review new approaches to induce death of latently infected cells through apoptosis and inhibition of pathways critical for cell survival, which are often hijacked by HIV proteins. Given advances in the commercial development of compounds that induce apoptosis in cancer chemotherapy, these agents could move rapidly into clinical trials, either alone or in combination with LRAs, to eliminate latent HIV infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA

    DEFF Research Database (Denmark)

    Greenaway, Christina; Pareek, Manish; Abou Chakra, Claire-Nour

    2018-01-01

    BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achie...

  5. Prevalence of latent tuberculosis and treatment adherence among patients with chronic kidney disease in Campo Grande, State of Mato Grosso do Sul

    Directory of Open Access Journals (Sweden)

    Aucely Corrêa Fernandes Chagas

    2014-04-01

    Full Text Available Introduction The primary strategy for tuberculosis control involves identifying individuals with latent tuberculosis. This study aimed to estimate the prevalence of latent tuberculosis in chronic kidney disease (CKD patients who were undergoing hemodialysis in Campo Grande, State of Mato Grosso do Sul, Brazil, to characterize the sociodemographic and clinical profiles of patients with latent tuberculosis, to verify the association between sociodemographic and clinical characteristics and the occurrence of latent tuberculosis, and to monitor patient adherence to latent tuberculosis treatment. Methods This epidemiological study involved 418 CKD patients who were undergoing hemodialysis and who underwent a tuberculin skin test. Results The prevalence of latent tuberculosis was 10.3%. The mean patient age was 53.43±14.97 years, and the patients were predominantly men (63.9%. The population was primarily Caucasian (58.6%; half (50% were married, and 49.8% had incomplete primary educations. Previous contact with tuberculosis patients was reported by 80% of the participants. Treatment adherence was 97.7%. Conclusions We conclude that the prevalence of latent tuberculosis in our study population was low. Previous contact with patients with active tuberculosis increased the occurrence of latent infection. Although treatment adherence was high in this study, it is crucial to monitor tuberculosis treatment administered to patients in health services to maintain this high rate.

  6. Establishment of HTLV-I-infected cell lines from peripheral blood mononuclear cells of Brazilian patients Estabelecimento de linhagens celulares infectadas por HTLV-I a partir de células mononucleares periféricas de pacientes brasileiros

    Directory of Open Access Journals (Sweden)

    Carolina V. Pannuti

    2004-08-01

    Full Text Available To investigate epidemiological and pathogenetic features of HTLV-I infection, a cohort of carriers has been followed at the USP Teaching Hospital since 1991. This study describes the establishment of cell lines from peripheral blood mononuclear cells (PBMC of infected subjects. Ex vivo PBMC were cultured with those from a seronegative donor and morphologic evidence of cell transformation was obtained after 90 days with detection of multinucleated cells exhibiting cerebriform nuclei. Integration of HTLV-I proviral DNA and expression of viral antigens was demonstrated in culture by PCR and immunofluorescence. Cell lines were maintained for 240 days, gradually weaned from exogenous IL-2. Immunophenotyping of cell lines on flow cytometry yielded evidence of cell activation. Establishment of HTLV-I-infected cell lines from ex vivo PBMC is feasible and may be useful for studies on lymphocyte phenotypic changes and on mechanisms of HTLV-induced cell proliferation. Moreover they may be used with diagnostic purposes in immunofluorescence tests.Para investigar a epidemiologia e patogênese da infecção por HTLV-I seguimos coorte de portadores dessa retrovirose no HC-FMUSP desde 1991. Este estudo descreve o estabelecimento de linhagens celulares a partir de células mononucleares periféricas (CMP de indivíduos infectados. As CMP foram cultivadas com as de doador soronegativo, verificando-se após 90 dias evidência morfológica de transformação celular com detecção de células multinucleadas com núcleos cerebriformes. Demonstrou-se integração do DNA proviral e expressão in vitro de antígenos virais pela PCR e imunofluorescência. As linhagens celulares transformadas foram mantidas por 240 dias, com retirada gradual de IL-2 exógena. A imunofenotipagem por citometria de fluxo revelou ativação celular. O estabelecimento de linhagens celulares infectadas por HTLV-I a partir de CMP ex-vivo é exeqüível e pode ser útil na investigação de

  7. Modeling Nonlinear Change via Latent Change and Latent Acceleration Frameworks: Examining Velocity and Acceleration of Growth Trajectories

    Science.gov (United States)

    Grimm, Kevin; Zhang, Zhiyong; Hamagami, Fumiaki; Mazzocco, Michele

    2013-01-01

    We propose the use of the latent change and latent acceleration frameworks for modeling nonlinear growth in structural equation models. Moving to these frameworks allows for the direct identification of "rates of change" and "acceleration" in latent growth curves--information available indirectly through traditional growth…

  8. Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1.

    Directory of Open Access Journals (Sweden)

    Geneviève Doyon

    Full Text Available Combination antiretroviral therapy (cART can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4(+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704 which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2. 57704 also increased HIV-1 expression in 3 of 4 CD8(+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110α isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency.

  9. Latent factors and route choice behaviour

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo

    . A reliable dataset was prepared through measures of internal consistency and sampling adequacy, and data were analyzed with a proper application of factor analysis to the route choice context. For the dataset obtained from the survey, six latent constructs affecting driver behaviour were extracted and scores...... on each factor for each survey participant were calculated. Path generation algorithms were examined with respect to observed behaviour, through a measure of reproduction with deterministic techniques of the routes indicated in the answers to the survey. Results presented evidence that the majority...... and Link Nested Logit. Estimates were produced from model specifications that considered level-of-service, label and facility dummy variables. Moreover, a modelling framework was designed to represent drivers’ choices as affected by the latent constructs extracted with factor analysis. Previous experience...

  10. Latent class models in financial data analysis

    Directory of Open Access Journals (Sweden)

    Attilio Gardini

    2007-10-01

    Full Text Available This paper deals with optimal international portfolio choice by developing a latent class approach based on the distinction between international and non-international investors. On the basis of micro data, we analyze the effects of many social, demographic, economic and financial characteristics on the probability to be an international investor. Traditional measures of equity home bias do not allow for the existence of international investment rationing operators. On the contrary, by resorting to latent class analysis it is possible to detect the unobservable distinction between international investors and investors who are precluded from operating into international financial markets and, therefore, to evaluate the role of these unobservable constraints on equity home bias.

  11. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    Science.gov (United States)

    Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

    2016-01-01

    The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  12. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    Directory of Open Access Journals (Sweden)

    Pedro Perdigão

    Full Text Available The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  13. Exploring galaxy evolution with latent space walks

    Science.gov (United States)

    Schawinski, Kevin; Turp, Dennis; Zhang, Ce

    2018-01-01

    We present a new approach using artificial intelligence to perform data-driven forward models of astrophysical phenomena. We describe how a variational autoencoder can be used to encode galaxies to latent space, independently manipulate properties such as the specific star formation rate, and return it to real space. Such transformations can be used for forward modeling phenomena using data as the only constraints. We demonstrate the utility of this approach using the question of the quenching of star formation in galaxies.

  14. Barcelona - Talent Latent 09 / Ahto Sooaru

    Index Scriptorium Estoniae

    Sooaru, Ahto

    2010-01-01

    Fotonäitusest "Talent Latent 09" Barcelonas Arts Santa Monica kunstikeskuses. Loetletud näitusel eksponeeritud fotode autorid. Pikemalt Rafael Milach'i (sünd. 1978), Lucia Ganieva, Javier Marquerie Thomas'i (sünd. 1986), Amaury da Cunha (sünd. 1976) töödest. Lühidalt ka teistest näitustest Arts Santa Monica kunstikeskuses

  15. Tuberculosis Screening and Active Tuberculosis among HIV-Infected Persons in a Canadian Tertiary Care Centre

    Directory of Open Access Journals (Sweden)

    Paul Brassard

    2009-01-01

    Full Text Available RATIONALE: HIV infection increases the risk of reactivation of latent tuberculosis (TB. The present study evaluates how latent TB is detected and treated to determine the effectiveness of screening in HIV-infected patients with diverse risk profiles.

  16. Identification of a new class of small molecules that efficiently reactivate latent Epstein-Barr virus

    Science.gov (United States)

    Tikhmyanova, Nadezhda; Schultz, David C.; Lee, Theresa; Salvino, Joseph M.; Lieberman, Paul M.

    2014-01-01

    Epstein-Barr Virus (EBV) persists as a latent infection in many lymphoid and epithelial malignancies, including Burkitt's lymphomas, nasopharyngeal carcinomas, and gastric carcinomas. Current chemotherapeutic treatments of EBV-positive cancers include broad- spectrum cytotoxic drugs that ignore the EBV-positive status of tumors. An alternative strategy, referred to as oncolytic therapy, utilizes drugs that stimulate reactivation of latent EBV to enhance the selective killing of EBV positive tumors, especially in combination with existing inhibitors of herpesvirus lytic replication, like Ganciclovir (GCV). At present, no small molecule, including histone deacetylase (HDAC) inhibitors, have proven safe or effective in clinical trials for treatment of EBV positive cancers. Aiming to identify new chemical entities that induce EBV lytic cycle, we have developed a robust high throughput cell-based assay to screen 66,840 small molecule compounds. Five structurally related tetrahydrocarboline derivatives were identified, two of which had EC50 measurements in the range of 150-170 nM. We show that these compounds reactivate EBV lytic markers ZTA and EA-D in all EBV-positive cell lines we have tested independent of the type of latency. The compounds reactivate a higher percentage of latently infected cells than HDAC inhibitors or phorbol esters in many cell types. The most active compounds showed low toxicity to EBV-negative cells, but were highly effective at selective cell killing of EBV-positive cells when combined with GCV. We conclude that we have identified a class of small molecule compounds that are highly effective at reactivating latent EBV infection in a variety of cell types, and show promise for lytic therapy in combination with GCV. PMID:24028149

  17. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells.

    Science.gov (United States)

    Huang, Szu-Han; Ren, Yanqin; Thomas, Allison S; Chan, Dora; Mueller, Stefanie; Ward, Adam R; Patel, Shabnum; Bollard, Catherine M; Cruz, Conrad Russell; Karandish, Sara; Truong, Ronald; Macedo, Amanda B; Bosque, Alberto; Kovacs, Colin; Benko, Erika; Piechocka-Trocha, Alicja; Wong, Hing; Jeng, Emily; Nixon, Douglas F; Ho, Ya-Chi; Siliciano, Robert F; Walker, Bruce D; Jones, R Brad

    2018-02-01

    The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells. Here, we have shown that treating CD4+ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8+ T cells recognized and potently eliminated CD4+ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8+ T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to CD8+ T cells that may need to be addressed to cure infection.

  18. Construction and Antiapoptosis Activities of Recombinant Adenoviral Expression Vector Carrying EBV Latent Membrane Protein 2A

    Directory of Open Access Journals (Sweden)

    Xishuang Liu

    2011-01-01

    Full Text Available To evaluate the possible effects of LMP2A (EBV latent membrane protein 2A on human gastric cancer cell line SGC-7901, LMP2A coding gene was subcloned into shuttle plasmid pAdTrackCMV to form transfer plasmid pAdTrackCMV-2A, which was linearized with PmeI and cotransformed into E.coli BJ5183 with adenovirus genomic plasmid of pAdeasy-1. The identified recombinant adenovirus plasmid DNA was digested with PacI and transfected into 293 cells to package recombinant adenovirus particles named vAd-2A. Then the expression and antiapoptosis activities of LMP2A on SGC-7901 infected with vAd-2A were analyzed. The vAd-2A was successfully constructed and identified by PCR, restriction digestion, and sequencing. LMP2A expression in SGC was identified by strong green fluorescence expression with fluorescence microscopic photograph and Southern blotting. The growth of LMP2A expressing SGC cells was apparently improved. Both cyclin E expression and S phase ratio in LMP2A expressing SGC cells were upregulated by cell cycle analysis and confocal microscopic analysis respectively. The replication-deficient recombinant adenovirus vector can express LMP2A antigen in SGC cells and inhibit their apoptosis. The results indicate that LMP2A might play an important role in pathogenesis of EBV-associated gastric cancer (EBVaGC. This study establishes a foundation for further study on EBVaGC and its gene therapy.

  19. Immune response to mycobacterial infection: lessons from flow cytometry.

    Science.gov (United States)

    Rovina, Nikoletta; Panagiotou, Marios; Pontikis, Konstantinos; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Koutsoukou, Antonia

    2013-01-01

    Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date.

  20. Immune Response to Mycobacterial Infection: Lessons from Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Nikoletta Rovina

    2013-01-01

    Full Text Available Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb at certain stages of infection as revealed by flow cytometry to date.

  1. Mental toughness latent profiles in endurance athletes.

    Directory of Open Access Journals (Sweden)

    Joanna S Zeiger

    Full Text Available Mental toughness in endurance athletes, while an important factor for success, has been scarcely studied. An online survey was used to examine eight mental toughness factors in endurance athletes. The study aim was to determine mental toughness profiles via latent profile analysis in endurance athletes and whether associations exist between the latent profiles and demographics and sports characteristics. Endurance athletes >18 years of age were recruited via social media outlets (n = 1245, 53% female. Mental toughness was measured using the Sports Mental Toughness Questionnaire (SMTQ, Psychological Performance Inventory-Alternative (PPI-A, and self-esteem was measured using the Rosenberg Self-Esteem Scale (RSE. A three-class solution emerged, designated as high mental toughness (High MT, moderate mental toughness (Moderate MT and low mental toughness (Low MT. ANOVA tests showed significant differences between all three classes on all 8 factors derived from the SMTQ, PPI-A and the RSE. There was an increased odds of being in the High MT class compared to the Low MT class for males (OR = 1.99; 95% CI, 1.39, 2.83; P<0.001, athletes who were over 55 compared to those who were 18-34 (OR = 2.52; 95% CI, 1.37, 4.62; P<0.01, high sports satisfaction (OR = 8.17; 95% CI, 5.63, 11.87; P<0.001, and high division placement (OR = 2.18; 95% CI, 1.46,3.26; P<0.001. The data showed that mental toughness latent profiles exist in endurance athletes. High MT is associated with demographics and sports characteristics. Mental toughness screening in athletes may help direct practitioners with mental skills training.

  2. LATENT STRUCTURE OF MOTOR ABILITIES AND SKILLS OF DEAF CHILDREN

    Directory of Open Access Journals (Sweden)

    Husnija Hasanbegović

    2012-04-01

    Full Text Available In this work surveys of latent motility abilities and skills of school children are shown. The sample for this survey was consisted of two subsamples. First one has consisted of deaf children N=29, and the second one has consisted hearing children of same age N=69. Subsamples of deaf is chosen according to model of applied sample, and subsample is chosen randomly, so two stages group sample N=90 has been created. After quantitative differences have been discovered between subsamples, hearing pupils have shown statistically better results at motility skills and techniques than deaf children and cumulative results have been subjected to inter correlation of variables. The target of using this method was determination of saturation of common variability through saturation of variables and their correlation by Ortoblique rotation for determination of latent information that are going to serve as practical guides at education and deaf children treatment, because of improvement of their motility abilities and skills according to hearing children. Three factors have been singled out as main preview of measurement on manifest variables. According to first review of measuring it has been established that at deaf children is needed to work on improving of physical abilities and mobility and then developed motility abilities and skills. Their information has been gained most probably by non system fluctuations as information about ability of balance maintaining which is most probably non dependable of motility abilities and skills as at deaf and hearing children too. According to this survey by entering the structure of measuring instrument it is possible to create programs for improving motility abilities and skills at deaf children.

  3. Using existing questionnaires in latent class analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Molgaard; Vach, Werner; Kent, Peter

    2016-01-01

    BACKGROUND: Latent class analysis (LCA) is increasingly being used in health research, but optimal approaches to handling complex clinical data are unclear. One issue is that commonly used questionnaires are multidimensional, but expressed as summary scores. Using the example of low back pain (LBP......), the aim of this study was to explore and descriptively compare the application of LCA when using questionnaire summary scores and when using single items to subgrouping of patients based on multidimensional data. MATERIALS AND METHODS: Baseline data from 928 LBP patients in an observational study were...

  4. Aspects of physicochemical methods for the detection of latent fingerprints

    International Nuclear Information System (INIS)

    Knowles, A.M.

    1978-01-01

    This paper reviews physicochemical methods of detecting latent finger-prints on a wide range of materials commonly found at the scene of a crime, with particular emphasis placed on the newer autoradiographic techniques. This is set against a description of studies on the fundamental nature of the latent fingerprint and its host substrate, with a brief review of the history of reagents used in latent fingerprint examination. (author)

  5. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

    Directory of Open Access Journals (Sweden)

    Caline G Matar

    2015-05-01

    Full Text Available Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68 infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission.

  6. A Framework for Reproducible Latent Fingerprint Enhancements.

    Science.gov (United States)

    Carasso, Alfred S

    2014-01-01

    Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

  7. Mental toughness latent profiles in endurance athletes.

    Science.gov (United States)

    Zeiger, Joanna S; Zeiger, Robert S

    2018-01-01

    Mental toughness in endurance athletes, while an important factor for success, has been scarcely studied. An online survey was used to examine eight mental toughness factors in endurance athletes. The study aim was to determine mental toughness profiles via latent profile analysis in endurance athletes and whether associations exist between the latent profiles and demographics and sports characteristics. Endurance athletes >18 years of age were recruited via social media outlets (n = 1245, 53% female). Mental toughness was measured using the Sports Mental Toughness Questionnaire (SMTQ), Psychological Performance Inventory-Alternative (PPI-A), and self-esteem was measured using the Rosenberg Self-Esteem Scale (RSE). A three-class solution emerged, designated as high mental toughness (High MT), moderate mental toughness (Moderate MT) and low mental toughness (Low MT). ANOVA tests showed significant differences between all three classes on all 8 factors derived from the SMTQ, PPI-A and the RSE. There was an increased odds of being in the High MT class compared to the Low MT class for males (OR = 1.99; 95% CI, 1.39, 2.83; Pathletes who were over 55 compared to those who were 18-34 (OR = 2.52; 95% CI, 1.37, 4.62; Pathletes. High MT is associated with demographics and sports characteristics. Mental toughness screening in athletes may help direct practitioners with mental skills training.

  8. Latent heat of traffic moving from rest

    Science.gov (United States)

    Farzad Ahmadi, S.; Berrier, Austin S.; Doty, William M.; Greer, Pat G.; Habibi, Mohammad; Morgan, Hunter A.; Waterman, Josam H. C.; Abaid, Nicole; Boreyko, Jonathan B.

    2017-11-01

    Contrary to traditional thinking and driver intuition, here we show that there is no benefit to ground vehicles increasing their packing density at stoppages. By systematically controlling the packing density of vehicles queued at a traffic light on a Smart Road, drone footage revealed that the benefit of an initial increase in displacement for close-packed vehicles is completely offset by the lag time inherent to changing back into a ‘liquid phase’ when flow resumes. This lag is analogous to the thermodynamic concept of the latent heat of fusion, as the ‘temperature’ (kinetic energy) of the vehicles cannot increase until the traffic ‘melts’ into the liquid phase. These findings suggest that in situations where gridlock is not an issue, drivers should not decrease their spacing during stoppages in order to lessen the likelihood of collisions with no loss in flow efficiency. In contrast, motion capture experiments of a line of people walking from rest showed higher flow efficiency with increased packing densities, indicating that the importance of latent heat becomes trivial for slower moving systems.

  9. Is there any role of latent toxoplasmosis in schizophrenia disease?

    Science.gov (United States)

    Karabulut, Nuran; Bilgiç, Serkan; Gürok, Mehmet Gürkan; Karaboğa, Fatih

    2015-09-01

    A large number of studies have hypothesized that Toxoplasma gondii is a potentially relevant etiological factor in some cases of schizophrenia. By contrast, some studies have disproved this association. The aim of this study was to investigate whether latent toxoplasmosis has any role in schizophrenia disease. Additionally, the association between T. gondii and subtypes of schizophrenia, and the impacts of toxoplasmosis on psychopathology were examined in the study. A total of 85 patients with schizophrenia and 60 healthy volunteers were included in this prospective study. Immunoglobulin G (IgG) antibody to T. gondii was examined by enzyme-linked immune-sorbent assay method. Seropositivity rates were 43.5% for the patients with schizophrenia and 43.3% for the healthy controls (odds ratio: 1.008, 95% confidence interval: 0.517-1.964, p = 0.981).There was no significant difference in T. gondii IgG positivity between the schizophrenia and control groups with respect to sex and age. The difference in seroprevalence of T. gondii IgG antibodies among the schizophrenia subtypes was not statistically significant (p = 0.934). No significant difference was found in Positive and Negative Syndrome Subscales between Toxoplasma-infected and Toxoplasma-free patients. In the study area with a high prevalence of T. gondii, no association between toxoplasmosis and schizophrenia was detected. These findings showed that toxoplasmosis has no role in the risk of schizophrenia disease. Copyright © 2015. Published by Elsevier Taiwan.

  10. A Latent Class Approach to Estimating Test-Score Reliability

    Science.gov (United States)

    van der Ark, L. Andries; van der Palm, Daniel W.; Sijtsma, Klaas

    2011-01-01

    This study presents a general framework for single-administration reliability methods, such as Cronbach's alpha, Guttman's lambda-2, and method MS. This general framework was used to derive a new approach to estimating test-score reliability by means of the unrestricted latent class model. This new approach is the latent class reliability…

  11. Intercept Centering and Time Coding in Latent Difference Score Models

    Science.gov (United States)

    Grimm, Kevin J.

    2012-01-01

    Latent difference score (LDS) models combine benefits derived from autoregressive and latent growth curve models allowing for time-dependent influences and systematic change. The specification and descriptions of LDS models include an initial level of ability or trait plus an accumulation of changes. A limitation of this specification is that the…

  12. A Review of the Latent and Manifest Benefits (LAMB) Scale

    Science.gov (United States)

    Muller, Juanita; Waters, Lea

    2012-01-01

    The latent and manifest benefits (LAMB) scale (Muller, Creed, Waters & Machin, 2005) was designed to measure the latent and manifest benefits of employment and provide a single scale to test Jahoda's (1981) and Fryer's (1986) theories of unemployment. Since its publication in 2005 there have been 13 studies that have used the scale with 5692…

  13. Prevalence and risk factors of latent Tuberculosis among ...

    African Journals Online (AJOL)

    Background: Latent Tuberculosis treatment is a key tuberculosis control intervention. Adolescents are a high risk group that is not routinely treated in low income countries. Knowledge of latent Tuberculosis (TB) burden among adolescents may influence policy. Objectives: We determined the prevalence and risk factors of ...

  14. Gene Variants Associated with Antisocial Behaviour: A Latent Variable Approach

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V.; Lee, Maria; Yrigollen, Carolyn M.; Pakstis, Andrew J.; Katsovich, Liliya; Olds, David L.; Grigorenko, Elena L.; Leckman, James F.

    2013-01-01

    Objective: The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods: Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a…

  15. Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells

    Science.gov (United States)

    Rac, Jürgen; Haas, Florian; Schumacher, Andrina; Middeldorp, Jaap M.; Delecluse, Henri-Jacques; Speck, Roberto F.

    2015-01-01

    The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is associated with epithelial malignancies including nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform epithelial cells in vitro where it is rapidly lost from infected primary epithelial cells or epithelial tumor cells. Long-term infection by EBV, however, can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here, we hypothesized that increased telomerase activity in epithelial cells enhances their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we generated epithelial model cell lines with increased or suppressed telomerase activity by stable ectopic expression of hTERT or of a catalytically inactive, dominant negative hTERT mutant. Infection experiments with recombinant prototypic EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able to undergo lytic replication, revealed that infection frequencies positively correlate with telomerase activity in AGS cells but also partly depend on the cellular background. AGS cells with increased telomerase activity showed increased expression mainly of latent EBV genes, suggesting that increased telomerase activity directly acts on the EBV infection of epithelial cells by facilitating latent EBV gene expression early upon virus inoculation. Thus, our results indicate that infection of epithelial cells by EBV is a very selective process involving, among others, telomerase activity and cellular background to allow for optimized host-to-host transmission via saliva. PMID:25856387

  16. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Dhananjay M Nawandar

    2015-10-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL in immunosuppressed patients. However, the cellular mechanism(s that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1 promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells.

  17. Tweets clustering using latent semantic analysis

    Science.gov (United States)

    Rasidi, Norsuhaili Mahamed; Bakar, Sakhinah Abu; Razak, Fatimah Abdul

    2017-04-01

    Social media are becoming overloaded with information due to the increasing number of information feeds. Unlike other social media, Twitter users are allowed to broadcast a short message called as `tweet". In this study, we extract tweets related to MH370 for certain of time. In this paper, we present overview of our approach for tweets clustering to analyze the users' responses toward tragedy of MH370. The tweets were clustered based on the frequency of terms obtained from the classification process. The method we used for the text classification is Latent Semantic Analysis. As a result, there are two types of tweets that response to MH370 tragedy which is emotional and non-emotional. We show some of our initial results to demonstrate the effectiveness of our approach.

  18. Iron appetite and latent learning in rats.

    Science.gov (United States)

    Woods, S C; Vasselli, J R; Milam, K M

    1977-11-01

    Two experiments are reported which show that rats are capable of forming an association between the presence of iron in a solution when it is not specifically needed and a subsequent state of iron deficiency. Specifically, rats were trained to lever press for water while thirsty. One group received ferrous ions in addition to the water. When these rats were subsequently rendered iron deficient, they lever pressed more under extinction conditions as a graded function of lower hemoglobin levels. Controls that either did not receive ferrous ions during training or received solutions other than ferrous solutions during training did not respond this way under extinction conditions. This is therefore a type of latent learning previously demonstrated only for sodium appetite.

  19. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study

    Directory of Open Access Journals (Sweden)

    Malý Marek

    2002-07-01

    Full Text Available Abstract Background The parasite Toxoplasma gondii infects 30–60% of humans worldwide. Latent toxoplasmosis, i.e., the life-long presence of Toxoplasma cysts in neural and muscular tissues, leads to prolongation of reaction times in infected subjects. It is not known, however, whether the changes observed in the laboratory influence the performance of subjects in real-life situations. Methods The seroprevalence of latent toxoplasmosis in subjects involved in traffic accidents (N = 146 and in the general population living in the same area (N = 446 was compared by a Mantel-Haenszel test for age-stratified data. Correlation between relative risk of traffic accidents and level of anti-Toxoplasma antibody titre was evaluated with the Cochran-Armitage test for trends. Results A higher seroprevalence was found in the traffic accident set than in the general population (Chi2MH = 21.45, p 95= 1.76–4.01 times higher risk of an accident than the toxoplasmosis-negative subjects. The OR significantly increased with level of anti-Toxoplasma antibody titre (p 95 = 1.14–3.03 for the 99 subjects with low antibody titres (8 and 16, higher (OR = 4.78, C.I.95 = 2.39–9.59 for the 37 subjects with moderate titres (32 and 64, and very high (OR = 16.03, C.I.95 = 1.89–135.66 for the 6 subjects with titres higher than 64. Conclusion The subjects with latent toxoplasmosis have significantly increased risk of traffic accidents than the noninfected subjects. Relative risk of traffic accidents decreases with the duration of infection. These results suggest that 'asymptomatic' acquired toxoplasmosis might in fact represent a serious and highly underestimated public health problem, as well as an economic problem.

  20. Latent Virus Reactivation in Space Shuttle Astronauts

    Science.gov (United States)

    Mehta, S. K.; Crucian, B. E.; Stowe, R. P.; Sams, C.; Castro, V. A.; Pierson, D. L.

    2011-01-01

    Latent virus reactivation was measured in 17 astronauts (16 male and 1 female) before, during, and after short-duration Space Shuttle missions. Blood, urine, and saliva samples were collected 2-4 months before launch, 10 days before launch (L-10), 2-3 hours after landing (R+0), 3 days after landing (R+14), and 120 days after landing (R+120). Epstein-Barr virus (EBV) DNA was measured in these samples by quantitative polymerase chain reaction. Varicella-zoster virus (VZV) DNA was measured in the 381 saliva samples and cytomegalovirus (CMV) DNA in the 66 urine samples collected from these subjects. Fourteen astronauts shed EBV DNA in 21% of their saliva samples before, during, and after flight, and 7 astronauts shed VZV in 7.4% of their samples during and after flight. It was interesting that shedding of both EBV and VZV increased during the flight phase relative to before or after flight. In the case of CMV, 32% of urine samples from 8 subjects contained DNA of this virus. In normal healthy control subjects, EBV shedding was found in 3% and VZV and CMV were found in less than 1% of the samples. The circadian rhythm of salivary cortisol measured before, during, and after space flight did not show any significant difference between flight phases. These data show that increased reactivation of latent herpes viruses may be associated with decreased immune system function, which has been reported in earlier studies as well as in these same subjects (data not reported here).

  1. Laser interrogation of latent vehicle registration number

    Energy Technology Data Exchange (ETDEWEB)

    Russo, R.E. [Lawrence Berkeley Lab., CA (United States). Energy and Environment Div.]|[Lawrence Livermore National Lab., CA (United States). Forensic Science Center; Pelkey, G.E. [City of Livermore Police Dept., CA (United States); Grant, P.; Whipple, R.E.; Andresen, B.D. [Lawrence Livermore National Lab., CA (United States). Forensic Science Center

    1994-09-01

    A recent investigation involved automobile registration numbers as important evidentiary specimens. In California, as in most states, small, thin metallic decals are issued to owners of vehicles each year as the registration is renewed. The decals are applied directly to the license plate of the vehicle and typically on top of the previous year`s expired decal. To afford some degree of security, the individual registration decals have been designed to tear easily; they cannot be separated from each other, but can be carefully removed intact from the metal license plate by using a razor blade. In September 1993, the City of Livermore Police Department obtained a blue 1993 California decal that had been placed over an orange 1992 decal. The two decals were being investigated as possible evidence in a case involving vehicle registration fraud. To confirm the suspicion and implicate a suspect, the department needed to known the registration number on the bottom (completely covered) 1992 decal. The authors attempted to use intense and directed light to interrogate the colored stickers. Optical illumination using a filtered white-light source partially identified the latent number. However, the most successful technique used a tunable dye laser pumped by a pulsed Nd:YAG laser. By selectively tuning the wavelength and intensity of the dye laser, backlit illumination of the decals permitted visualization of the underlying registration number through the surface of the top sticker. With optimally-tuned wavelength and intensity, 100% accuracy was obtained in identifying the sequence of latent characters. The advantage of optical techniques is their completely nondestructive nature, thus preserving the evidence for further interrogation or courtroom presentation.

  2. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

    Science.gov (United States)

    Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

    1982-11-01

    Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.

  3. Tratamento da tuberculose de infecção latente. As recomendações actuais

    Directory of Open Access Journals (Sweden)

    R. Duarte

    2010-09-01

    Full Text Available Resumo: O diagnóstico e tratamento da infecção latente por Mycobacterium tuberculosis reduz significativamente o risco de desenvolvimento de tuberculose activa e a transmissão da doença na comunidade. O rastreio da tuberculose infecção latente deve passar pela exclusão de doença activa (inquérito de sintomas e radiografia pulmonar e avaliação da resposta imunológica ao M. tuberculosis através dos testes actualmente ao dispor, como o teste tuberculínico e os testes IGRA (interferon-gamma release assay. A escolha do esquema de tratamento deve ter em linha de conta a eficácia, a adesão e os efeitos colaterais associados ao mesmo Este documento actualiza as recomendações sobre tratamento da tuberculose infecção latente. São apresentadas indicações sobre quem deve ser rastreado e revistos os esquemas de tratamento.Rev Port Pneumol 2010; XVI (5: 809-814 Abstract: Diagnosis and tr