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Sample records for acute ebv infection

  1. EBV Chronic Infections

    PubMed Central

    Eligio, Pizzigallo; Delia, Racciatti; Valeria, Gorgoretti

    2010-01-01

    these studies it was possibile to confirm the etiologic links between the syndrome and EBV or other herpesviruses or other persistent infectious agents. The mechanisms of EBV latency have been carefully examined both because they represent the virus strategy to elude the response of the immune system of the host, and because they are correlated with those oncologic conditions associated to the viral persistence, particularly lymphomas and lymphoproliferative disorders. Just these malignancies, for which a pathogenetic role of EBV is clearly documented, should represent the main clinical expression of a first group of chronic EBV infections characterized by a natural history where the neoplastic event aroused from the viral persistence in the resting B cells for all the life, from the genetic predisposition of the host and from the oncogenic potentialities of the virus that chronically persists and incurs reactivations. Really, these oncological diseases should be considered more complications than chronic forms of the illness, as well as other malignancies for which a viral – or even infectious - etiology is well recognized. The chronic diseases, in fact, should be linked in a pathogenetic and temporal way to the acute infection, from whom start the natural history of the following disease. So, as for the chronic liver diseases from HBV and HCV, it was conied the acronym of CAEBV (Chronic Active EBV infection), distinguishing within these pathologies the more severe forms (SCAEBV) mostly reported in Far East and among children or adolescents. Probably only these forms have to be considered expressions of a chronic EBV infection “sensu scrictu”, together with those forms of CFS where the etiopathogenetic and temporal link with the acute EBV infection is well documented. As for CFS, also for CAEBV the criteria for a case definition were defined, even on the basis of serological and virological findings. However, the lymphoproliferative disorders are excluded from

  2. An Epstein-Barr Virus Encoded Inhibitor of Colony Stimulating Factor-1 Signaling Is an Important Determinant for Acute and Persistent EBV Infection

    PubMed Central

    Ohashi, Makoto; Fogg, Mark H.; Orlova, Nina; Quink, Carol; Wang, Fred

    2012-01-01

    Acute Epstein-Barr virus (EBV) infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1) signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV), naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1). Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection. PMID:23300447

  3. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis

    PubMed Central

    Hadinoto, Vey; Shapiro, Michael; Greenough, Thomas C.; Sullivan, John L.; Luzuriaga, Katherine

    2008-01-01

    Memory B cells latently infected with Epstein-Barr virus (mBLats) in the blood disappear rapidly on presentation with acute symptomatic primary infection (acute infectious mononucleosis [AIM]). They undergo a simple exponential decay (average half-life: 7.5 ± 3.7 days) similar to that of normal memory B cells. The cytotoxic T lymphocyte (CTL) response to immediate early (IE) lytic antigens (CTLIEs) also decays over this time period, but no such correlation was observed for the CTL response to lytic or latent antigens or to the levels of virions shed into saliva. We have estimated the average half-life of CTLIEs to be 73 (± 23) days. We propose that cycles of infection and reactivation occur in the initial stages of infection that produce high levels of mBLats in the circulation. Eventually the immune response arises and minimizes these cycles leaving the high levels of mBLats in the blood to decay through simple memory B-cell homeostasis mechanisms. This triggers the cells to reactivate the virus whereupon most are killed by CTLIEs before they can release virus and infect new cells. The release of antigens caused by this large-scale destruction of infected cells may trigger the symptoms of AIM and be a cofactor in other AIM-associated diseases. PMID:17991806

  4. Quercetin-induced apoptosis prevents EBV infection

    PubMed Central

    Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

    2015-01-01

    Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma

  5. Simultaneous genital ulcer and meningitis: a case of EBV infection

    PubMed Central

    Nunes, Jairo Tavares; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2016-01-01

    The Epstein-Barr virus (EBV) is associated with a broad spectrum of diseases, mainly because of its genomic characteristics, which result in different latency patterns in immune cells and infective mechanisms. The patient described in this report is a previously healthy young man who presented to the emergency department with clinical features consistent with meningitis and genital ulcers, which raised concern that the herpes simplex virus was the causative agent. However, the polymerase chain reaction of cerebral spinal fluid was positive for EBV. The authors highlight the importance of this infection among the differential diagnosis of central nervous system involvement and genital ulceration. PMID:27547743

  6. Simultaneous genital ulcer and meningitis: a case of EBV infection.

    PubMed

    Rahhal, Hassan; Nunes, Jairo Tavares; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2016-01-01

    The Epstein-Barr virus (EBV) is associated with a broad spectrum of diseases, mainly because of its genomic characteristics, which result in different latency patterns in immune cells and infective mechanisms. The patient described in this report is a previously healthy young man who presented to the emergency department with clinical features consistent with meningitis and genital ulcers, which raised concern that the herpes simplex virus was the causative agent. However, the polymerase chain reaction of cerebral spinal fluid was positive for EBV. The authors highlight the importance of this infection among the differential diagnosis of central nervous system involvement and genital ulceration. PMID:27547743

  7. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells.

    PubMed

    Wang, Hong-Bo; Zhang, Hua; Zhang, Jing-Ping; Li, Yan; Zhao, Bo; Feng, Guo-Kai; Du, Yong; Xiong, Dan; Zhong, Qian; Liu, Wan-Li; Du, Huamao; Li, Man-Zhi; Huang, Wen-Lin; Tsao, Sai Wah; Hutt-Fletcher, Lindsey; Zeng, Yi-Xin; Kieff, Elliott; Zeng, Mu-Sheng

    2015-01-01

    Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB(23-431). Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. PMID:25670642

  8. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells

    PubMed Central

    Wang, Hong-Bo; Zhang, Hua; Zhang, Jing-Ping; Li, Yan; Zhao, Bo; Feng, Guo-Kai; Du, Yong; Xiong, Dan; Zhong, Qian; Liu, Wan-Li; Du, Huamao; Li, Man-Zhi; Huang, Wen-Lin; Tsao, Sai Wah; Hutt-Fletcher, Lindsey; Zeng, Yi-Xin; Kieff, Elliott; Zeng, Mu-Sheng

    2015-01-01

    Epstein–Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB23–431. Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. PMID:25670642

  9. EBV-associated B- and T-cell posttransplant lymphoproliferative disorders following primary EBV infection in a kidney transplant recipient.

    PubMed

    Yin, C Cameron; Medeiros, L Jeffrey; Abruzzo, Lynne V; Jones, Dan; Farhood, Anwar I; Thomazy, Vilmos A

    2005-02-01

    Posttransplant lymphoproliferative disorders (PTLDs) usually are of B-cell lineage and associated with Epstein-Barr virus (EBV). PTLDs of T-cell lineage are much less common and infrequently associated with EBV. We report a rare case of a girl in whom B-cell and T-cell PTLDs developed following 2 EBV-negative kidney transplants. Within 2 years of the second transplantation, the originally EBV-negative patient developed both an EBV-associated clonal B-cell PTLD involving lymph nodes and an EBV-positive T-cell PTLD involving bone marrow and liver. These proliferations occurred concurrently with evidence of primary EBV infection and high plasma viral load. The patient eventually died of multiorgan failure 5 years after the initial transplant (3 years after the second transplant). To our knowledge, only 4 cases of both B-cell and T-cell PTLDs have been reported. Only 2 cases have been proven to be monoclonal and EBV-associated, as in this case, the first following kidney transplantation. PMID:15842046

  10. Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth

    PubMed Central

    Noh, Ka-Won; Park, Jihyun; Kang, Myung-Soo

    2016-01-01

    Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt’s lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders. [BMB Reports 2016; 49(4): 226-231] PMID:26879316

  11. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

    PubMed

    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID:26687013

  12. Human Antibody Titers to Epstein-Barr Virus (EBV) gp350 Correlate with Neutralization of Infectivity Better than Antibody Titers to EBV gp42 Using a Rapid Flow Cytometry-Based EBV Neutralization Assay

    PubMed Central

    Sashihara, Junji; Burbelo, Peter D.; Savoldo, Barbara; Pierson, Theodore C.; Cohen, Jeffrey I.

    2009-01-01

    Measurement of neutralizing antibodies to Epstein-Barr virus (EBV) is important for evaluation of candidate vaccines. The current neutralization assay is based on antibody inhibition of EBV transformation of B cells and requires 6 weeks to perform. We developed a rapid, quantitative flow cytometry assay and show that neutralizing antibody titers measured by the new assay strongly correlate with antibody titers in the standard transformation-based assay. Antibodies to EBV gp350 and gp42 have been shown to block infection of B cells by EBV. Using new assays to quantify antibodies to these glycoproteins, we show for the first time that that human plasma contains high titers of antibody to gp42; these titers correlate with neutralization of EBV infectivity or transformation. Furthermore, we show that antibody titers to EBV gp350 correlate more strongly with neutralization than antibody titers to gp42. These assays should be useful in accessing antibody responses to candidate EBV vaccines. PMID:19584018

  13. Modeling EBV infection and pathogenesis in new-generation humanized mice

    PubMed Central

    Fujiwara, Shigeyoshi; Imadome, Ken-Ichi; Takei, Masami

    2015-01-01

    The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein–Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described. PMID:25613732

  14. Epstein-Barr Virus Infection with Acute Acalculous Cholecystitis

    PubMed Central

    Kim, Ahlee; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-01-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  15. Epstein-barr virus infection with acute acalculous cholecystitis.

    PubMed

    Kim, Ahlee; Yang, Hye Ran; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-03-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  16. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.

    PubMed Central

    Calender, A; Billaud, M; Aubry, J P; Banchereau, J; Vuillaume, M; Lenoir, G M

    1987-01-01

    A set of B-cell activation markers, including the EBV/C3d receptor [complement receptor type 2 (CR2) (CD21)], the 45-kDa lymphoblastoid cell-associated (Blast-2) antigen (CD23), and the B-cell restricted activation (Bac-1) antigen (which was recently identified as a potential B-cell growth factor receptor) can be turned on by infecting lymphoma cells that are genome negative for Epstein-Barr virus (EBV) with the B95-8 immortalizing strain of the virus. The nonimmortalizing EBV variant, strain P3HR-1, which possesses a deletion within the BamHI WYH region of the genome containing the coding sequence for the EBV-determined nuclear antigen 2, does not induce expression of these markers. Other lymphoblastoid cell-associated antigen markers can be activated by infection with either immortalizing or nonimmortalizing viruses. These results suggest that the immortalizing potential of EBV is correlated with its ability to induce expression of B-cell activation markers, which are suspected to play a major role in the physiological pathway leading to lymphoid cell proliferation. The viral genomic region deleted in the nonimmortalizing strain of EBV seems to be required for activation of some of these markers. Human lymphoma cell lines, such as those used in this study, can thus help identify the specific EBV genes involved in lymphoid B-cell proliferation and the mechanism of action of these genes. PMID:2825176

  17. Sensing of latent EBV infection through exosomal transfer of 5'pppRNA.

    PubMed

    Baglio, S Rubina; van Eijndhoven, Monique A J; Koppers-Lalic, Danijela; Berenguer, Jordi; Lougheed, Sinéad M; Gibbs, Susan; Léveillé, Nicolas; Rinkel, Rico N P M; Hopmans, Erik S; Swaminathan, Sankar; Verkuijlen, Sandra A W M; Scheffer, George L; van Kuppeveld, Frank J M; de Gruijl, Tanja D; Bultink, Irene E M; Jordanova, Ekaterina S; Hackenberg, Michael; Piersma, Sander R; Knol, Jaco C; Voskuyl, Alexandre E; Wurdinger, Thomas; Jiménez, Connie R; Middeldorp, Jaap M; Pegtel, D Michiel

    2016-02-01

    Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein-Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with the lupus antigen (La) ribonucleoprotein, avoiding cytoplasmic RNA sensors. However, in coculture experiments we observed that latent-infected cells trigger antiviral immunity in dendritic cells (DCs) through selective release and transfer of RNA via exosomes. In ex vivo tonsillar cultures, we observed that EBER1-loaded exosomes are preferentially captured and internalized by human plasmacytoid DCs (pDCs) that express the TIM1 phosphatidylserine receptor, a known viral- and exosomal target. Using an EBER-deficient EBV strain, enzymatic removal of 5'ppp, in vitro transcripts, and coculture experiments, we established that 5'pppEBER1 transfer via exosomes drives antiviral immunity in nonpermissive DCs. Lupus erythematosus patients suffer from elevated EBV load and activated antiviral immunity, in particular in skin lesions that are infiltrated with pDCs. We detected high levels of EBER1 RNA in such skin lesions, as well as EBV-microRNAs, but no intact EBV-DNA, linking non-cell-autonomous EBER1 presence with skin inflammation in predisposed individuals. Collectively, our studies indicate that virus-modified exosomes have a physiological role in the host-pathogen stand-off and may promote inflammatory disease. PMID:26768848

  18. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    SciTech Connect

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  19. Sensing of latent EBV infection through exosomal transfer of 5′pppRNA

    PubMed Central

    Baglio, S. Rubina; van Eijndhoven, Monique A. J.; Koppers-Lalic, Danijela; Berenguer, Jordi; Lougheed, Sinéad M.; Gibbs, Susan; Léveillé, Nicolas; Rinkel, Rico N. P. M.; Hopmans, Erik S.; Swaminathan, Sankar; Verkuijlen, Sandra A. W. M.; Scheffer, George L.; van Kuppeveld, Frank J. M.; de Gruijl, Tanja D.; Bultink, Irene E. M.; Jordanova, Ekaterina S.; Hackenberg, Michael; Piersma, Sander R.; Knol, Jaco C.; Voskuyl, Alexandre E.; Wurdinger, Thomas; Jiménez, Connie R.; Middeldorp, Jaap M.; Pegtel, D. Michiel

    2016-01-01

    Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein–Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with the lupus antigen (La) ribonucleoprotein, avoiding cytoplasmic RNA sensors. However, in coculture experiments we observed that latent-infected cells trigger antiviral immunity in dendritic cells (DCs) through selective release and transfer of RNA via exosomes. In ex vivo tonsillar cultures, we observed that EBER1-loaded exosomes are preferentially captured and internalized by human plasmacytoid DCs (pDCs) that express the TIM1 phosphatidylserine receptor, a known viral- and exosomal target. Using an EBER-deficient EBV strain, enzymatic removal of 5′ppp, in vitro transcripts, and coculture experiments, we established that 5′pppEBER1 transfer via exosomes drives antiviral immunity in nonpermissive DCs. Lupus erythematosus patients suffer from elevated EBV load and activated antiviral immunity, in particular in skin lesions that are infiltrated with pDCs. We detected high levels of EBER1 RNA in such skin lesions, as well as EBV-microRNAs, but no intact EBV-DNA, linking non–cell-autonomous EBER1 presence with skin inflammation in predisposed individuals. Collectively, our studies indicate that virus-modified exosomes have a physiological role in the host–pathogen stand-off and may promote inflammatory disease. PMID:26768848

  20. Epstein-Barr Virus (EBV)-Associated Haemophagocytic Syndrome

    PubMed Central

    Torti, Lorenza; Larocca, Luigi M.; Massini, Giuseppina; Cuccaro, Annarosa; Maiolo, Elena; Santangelo, Rosaria; Bianchi, Maria; Pennisi, Mariano Alberto; Hohaus, Stefan; Teofili, Luciana

    2012-01-01

    We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS) one month following acute infection caused by Epstein-Barr virus (EBV). Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection. PMID:22348190

  1. Ear infection - acute

    MedlinePlus

    Otitis media - acute; Infection - inner ear; Middle ear infection - acute ... Casselbrandt ML, Mandel EM. Acute otitis media and otitis media with effusion. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  2. Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice

    PubMed Central

    Gregorovic, Goran; Boulden, Elizabeth A.; Bosshard, Rachel; Elgueta Karstegl, Claudio; Skalsky, Rebecca; Cullen, Bryan R.; Gujer, Cornelia; Rämer, Patrick; Münz, Christian

    2015-01-01

    Functions of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were tested in lymphoblastoid cell lines containing EBER mutants of EBV. Binding of EBER1 to ribosomal protein L22 (RPL22) was confirmed. Deletion of EBER1 or EBER2 correlated with increased levels of cytoplasmic EBV LMP2 RNA and with small effects on specific cellular microRNA (miRNA) levels, but protein levels of LMP1 and LMP2A were not affected. Wild-type EBV and EBER deletion EBV had approximately equal abilities to infect immunodeficient mice reconstituted with a human hematopoietic system. PMID:26339045

  3. Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice.

    PubMed

    Gregorovic, Goran; Boulden, Elizabeth A; Bosshard, Rachel; Elgueta Karstegl, Claudio; Skalsky, Rebecca; Cullen, Bryan R; Gujer, Cornelia; Rämer, Patrick; Münz, Christian; Farrell, Paul J

    2015-11-01

    Functions of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were tested in lymphoblastoid cell lines containing EBER mutants of EBV. Binding of EBER1 to ribosomal protein L22 (RPL22) was confirmed. Deletion of EBER1 or EBER2 correlated with increased levels of cytoplasmic EBV LMP2 RNA and with small effects on specific cellular microRNA (miRNA) levels, but protein levels of LMP1 and LMP2A were not affected. Wild-type EBV and EBER deletion EBV had approximately equal abilities to infect immunodeficient mice reconstituted with a human hematopoietic system. PMID:26339045

  4. Invasive Fusobacterium necrophorum infections and Lemièrre's syndrome: the role of thrombophilia and EBV.

    PubMed

    Holm, K; Svensson, P J; Rasmussen, M

    2015-11-01

    The purpose of this investigation was to describe the clinical spectrum of invasive Fusobacterium necrophorum infections and Lemièrre's syndrome, to examine the role of underlying thrombophilia and concomitant mononucleosis in Lemièrre's syndrome, and to describe thromboembolic complications. Patients with invasive F. necrophorum infections were identified either prospectively or retrospectively through the regional database of clinical microbiology from 2000 to 2015. Patient records were reviewed and blood samples from patients with Lemièrre's syndrome were collected for Epstein-Barr virus (EBV) serology and screening for thrombophilia. Of the 65 patients included, 33 had Lemièrre's syndrome. Of the remaining 32 patients, other infections of the respiratory tract and abdominal or urogenital infections were most common. Patients with Lemièrre's syndrome or other tonsillar infections were younger than patients from the other groups. For Lemièrre's syndrome, the 26 patients with severe sepsis on admittance had longer duration of symptoms. Three of five patients who developed distant manifestations had more than 14 days of symptoms. Jugular vein thrombosis was verified in 14 patients, two of whom developed serious complications. Three of 26 patients tested had factor V Leiden mutation, corresponding to the background prevalence. One of 22 patients tested had a concomitant EBV infection. This study confirms earlier studies of the clinical spectrum caused by F. necrophorum. For Lemièrre's syndrome, the study adds to the knowledge on thromboembolic outcome, demonstrating that jugular vein thrombosis may cause severe complications. The time to treatment seems to be important for the risk of severe disease. In this study, concomitant EBV infection or underlying thrombophilia was uncommon. PMID:26272176

  5. Radiculoplexopathy with conduction block caused by acute Epstein-Barr virus infection.

    PubMed

    Vucic, Steve; Palmer, William; Cros, Didier

    2005-02-01

    The authors report a case of cervicobrachial radiculoplexopathy with proximal conduction block (CB), associated with acute Epstein-Barr virus (EBV) infection. The patient presented with pain, paresthesias, and monomelic weakness in the left C7-8, and T1 myotomes. The illness was monophasic with rapid recovery. Neurophysiologic studies demonstrated CB in the proximal left median and ulnar nerve segments. The authors conclude that this syndrome resulted from a postinfectious process following acute EBV infection. PMID:15699388

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

    PubMed

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

    1992-12-01

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

  7. Aggressive Peripheral CD70-positive T-cell Lymphoma Associated with Severe Chronic Active EBV Infection

    PubMed Central

    Shaffer, Donald R.; Sheehan, Andrea M.; Yi, Zhongzhen; Rodgers, Cheryl C; Bollard, Catherine M; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Gottschalk, Stephen

    2011-01-01

    Severe chronic active Epstein-Barr virus infection (CAEBV) in T or NK cells is a rare complication of latent EBV infection. CAEBV associated T-cell lymphoproliferative disease (LPD) consists of polyclonal lesions as well as aggressive lymphomas. Here we report such a patient. In addition, we show that this primary CAEBV associated T-cell lymphoma expresses CD70 and is sensitive to killing by CD70-specific T cells, identifying CD70 as a potential immunotherapeutic target for CAEBV-associated T-cell lymphoma. PMID:21994111

  8. Genipin as a novel chemical activator of EBV lytic cycle.

    PubMed

    Son, Myoungki; Lee, Minjung; Ryu, Eunhyun; Moon, Aree; Jeong, Choon-Sik; Jung, Yong Woo; Park, Gyu Hwan; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

    2015-02-01

    Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC. PMID:25626372

  9. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Morales-Sánchez, A.; Pompa-Mera, E. N.; Fajardo-Gutiérrez, A.; Alvarez-Rodríguez, F. J.; Bekker-Méndez, V. C.; Flores-Chapa, J. de Diego; Flores-Lujano, J.; Jiménez-Hernández, E.; Peñaloza-González, J. G.; Rodríguez-Zepeda, M. C.; Torres-Nava, J. R.; Velázquez-Aviña, M. M.; Amador-Sánchez, R.; Alvarado-Ibarra, M.; Reyes-Zepeda, N.; Espinosa-Elizondo, R. M.; Pérez-Saldivar, M. L.; Núñez-Enríquez, J. C.; Mejía-Aranguré, J. M.; Fuentes-Pananá, E. M.

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. PMID:25309913

  10. EBV-Positive Grey Zone Lymphoma in an HIV Infected Man from Kampala, Uganda: Case Report

    PubMed Central

    Tumwine, Lynette K.; Orem, Jackson; Ayers, Leona W.

    2014-01-01

    Aim We describe the clinical, histopathological and immunophenotypic characteristics of an HIV-infected adult man on antiretroviral therapy who presented with an EBV-positive grey zone lymphoma. Case presentation A 56-year-old HIV infected man from Uganda presented with a four month history of progressive abdominal swelling and B-symptoms. He was on highly active antiretroviral therapy (HAART) and cotrimoxazole. He was afebrile (36.9°C), severely wasted (BMI 14.8), and mildly anaemic. On physical examination, he had a 15 by 8 cm mass in the hypogastrium and umbilical region. The total white cell count was 8.3×103/μL; neutrophils, 5.72×103/μL; haemoglobin 11.1g/dL, platelets 528×103/μL, LDH 197 IU/L and CD4 367/μL. Abdominal ultrasound and CT scan showed a tumour involving the mesentery, jejunum and mid ileum. At laparotomy, a biopsy was taken, fixed, processed and stained with Haematoxylin & Eosin (H & E). Histopathology demonstrated large pleomorphic cells admixed with inflammatory smaller cells, Reed-Sternberg-like cell variants and frequent abnormal mitoses. Biomarkers CD20, PAX5, CD30 were positive but ALK negative (immunohistochemistry and strong EBER positivity in situ hybridization. The patient improved on modified CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Discussion The tumour had features intermediate between mediastinal large B cell lymphoma and classical Hodgkin lymphoma. Conclusion We present a case of EBV-positive grey zone lymphoma in an HIV-infected man on HAART therapy diagnosed and treated in a resource constrained medical setting. The histological features are unusual and represent a low incidence lymphoma that is recognized by mixed features reminiscent of Hodgkin’s lymphoma and mediastinal large B-cell lymphoma. PMID:25599090

  11. EBV Noncoding RNAs.

    PubMed

    Skalsky, Rebecca L; Cullen, Bryan R

    2015-01-01

    EBV expresses a number of viral noncoding RNAs (ncRNAs) during latent infection, many of which have known regulatory functions and can post-transcriptionally regulate viral and/or cellular gene expression. With recent advances in RNA sequencing technologies, the list of identified EBV ncRNAs continues to grow. EBV-encoded RNAs (EBERs) , the BamHI-A rightward transcripts (BARTs) , a small nucleolar RNA (snoRNA) , and viral microRNAs (miRNAs) are all expressed during EBV infection in a variety of cell types and tumors. Recently, additional novel EBV ncRNAs have been identified. Viral miRNAs, in particular, have been under extensive investigation since their initial identification over ten years ago. High-throughput studies to capture miRNA targets have revealed a number of miRNA-regulated viral and cellular transcripts that tie into important biological networks. Functions for many EBV ncRNAs are still unknown; however, roles for many EBV miRNAs in latency and in tumorigenesis have begun to emerge. Ongoing mechanistic studies to elucidate the functions of EBV ncRNAs should unravel additional roles for ncRNAs in the viral life cycle. In this chapter, we will discuss our current knowledge of the types of ncRNAs expressed by EBV, their potential roles in viral latency, and their potential involvement in viral pathogenesis. PMID:26428375

  12. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  13. EBV and Autoimmunity.

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2015-01-01

    Although a role of EBV in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been possible only for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE), whereas evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify the conclusion that EBV is a component cause of MS and SLE and possible mechanisms underlying these effects. PMID:26424654

  14. Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation.

    PubMed

    Germi, Raphaële; Guigue, Nicolas; Lupo, Julien; Semenova, Touyana; Grossi, Laurence; Vermeulen, Odile; Epaulard, Olivier; de Fraipont, Florence; Morand, Patrice

    2016-10-01

    During Epstein-Barr virus (EBV) latency, the EBV genome is largely silenced by methylation. This silencing is overturned during the switch to the lytic cycle. A key event is the production of the viral protein Zta which binds to three Zta-response elements (ZRE) from the Rta promoter (Rp), two of which (ZRE2 and ZRE3) include three CpG motifs methylated in the latent genome. The bisulphite pyrosequencing reaction was used to quantify the methylation of ZRE2, ZRE3a, and ZRE3b in EBV-positive cell lines and in ex vivo samples of EBV-related diseases, in order to assess whether the level of methylation in these ZREs could provide additional information to viral DNA load and serology in the characterization of EBV-associated diseases. In PBMC from two patients with infectious mononucleosis, over time Rp became increasingly methylated whereas EBV load decreased. In tonsil from patients with chronic tonsillitis, the methylation was less than in EBV-associated tumors, regardless of the viral load. This was even more striking when only the ZRE3a and ZRE3b were considered since some samples presented unbalanced profiles on ZRE2. EBV reactivation in cell culture showed that the reduction in the overall level of methylation was closely related to the production of unmethylated virions. Thus, an assessment of the level of methylation may help to better characterize EBV replication in PBMC and in biopsies with high EBV load, during infectious mononucleosis and EBV-associated cancers. J. Med. Virol. 88:1814-1820, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990870

  15. Identification of Epstein-Barr Virus (EBV) Nuclear Antigen 2 (EBNA2) Target Proteins by Proteome Analysis: Activation of EBNA2 in Conditionally Immortalized B Cells Reflects Early Events after Infection of Primary B Cells by EBV

    PubMed Central

    Schlee, Martin; Krug, Tanja; Gires, Olivier; Zeidler, Reinhard; Hammerschmidt, Wolfgang; Mailhammer, Reinhard; Laux, Gerhard; Sauer, Guido; Lovric, Josip; Bornkamm, Georg W.

    2004-01-01

    The Epstein-Barr virus (EBV) is a ubiquitous B-lymphotropic herpesvirus associated with several malignant tumors, e.g., Burkitt's lymphoma and Hodgkin's disease, and is able to efficiently immortalize primary B lymphocytes in vitro. The growth program of infected B cells is initiated and maintained by the viral transcription factor EBV nuclear antigen 2 (EBNA2), which regulates viral and cellular genes, including the proto-oncogene c-myc. In our study, patterns of protein expression in B cells with and without EBNA2 were analyzed by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. For this purpose, we used a conditional immortalization system for EBV, a B cell line (EREB2-5) that expresses an estrogen receptor-EBNA2 fusion protein. In order to discriminate downstream targets of c-Myc from c-Myc-independent EBNA2 targets, we used an EREB2-5-derived cell line, P493-6, in which c-Myc is expressed under the control of a tetracycline-regulated promoter. Of 20 identified EBNA2 target proteins, 11 were c-Myc dependent and therefore most probably associated with proliferation, and one of these proteins was a posttranslationally modified protein, i.e., hypusinylated eIF5a. Finally, to estimate the relevance of EBNA2 targets during early EBV infection, we analyzed the proteomes of primary B cells before and after infection with EBV. The protein expression pattern induced upon EBV infection was similar to that following EBNA2 activation. These findings underscore the value of EREB2-5 cells as an appropriate model system for the analysis of early events in the process of EBV-mediated B-cell immortalization. PMID:15047810

  16. Acute Acalculous Cholecystitis by Epstein-Barr Virus Infection: A Rare Association

    PubMed Central

    Vieira, Maria; Couto, Cristiana; Coelho, Maria D.; Laranjeira, Carla

    2015-01-01

    Acute acalculous cholecystitis (AAC) is a rare complication of Epstein Barr virus (EBV) infection, with only a few cases reported among pediatric population. This clinical condition is frequently associated with a favorable outcome and, usually, a surgical intervention is not required. We report a 16-year-old girl who presented with AAC following primary EBV infection. The diagnosis of AAC was documented by clinical and ultrasonographic examination, whereas EBV infection was confirmed serologically. A conservative treatment was performed, with a careful monitoring and serial ultrasonographic examinations, which led to the clinical improvement of the patient. Pediatricians should be aware of the possible association between EBV and AAC, in order to offer the patients an appropriate management strategy. PMID:26753086

  17. Detection and quantification of Epstein-Barr virus EBER1 in EBV-infected cells by fluorescent in situ hybridization and flow cytometry

    NASA Technical Reports Server (NTRS)

    Stowe, R. P.; Cubbage, M. L.; Sams, C. F.; Pierson, D. L.; Barrett, A. D.

    1998-01-01

    A rapid and highly sensitive fluorescent in situ hybridization (FISH) assay was developed to detect Epstein Barr virus (EBV)-infected cells in peripheral blood. Multiple fluorescein-labeled antisense oligonucleotide probes were designed to hybridize to the EBER1 transcript, which is highly expressed in latently infected cells. After a rapid (30 min) hybridization, the cells were analyzed by flow cytometry. EBER1 was detected in several positive control cell lines that have variable numbers of EBV genome copies. No EBER1 was detected in two known EBV-negative cell lines. Northern blot analyses confirmed the presence and quantity of EBER1 transcripts in each cell line. This method was used to quantify the number of EBV-infected cells in peripheral blood from a patient with chronic mononucleosis. These results indicate that EBV-infected cells can be detected at the single cell level, and that this assay can be used to quantify the number of EBV-infected cells in clinical samples.

  18. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia.

    PubMed

    Styczynski, J; Reusser, P; Einsele, H; de la Camara, R; Cordonnier, C; Ward, K N; Ljungman, P; Engelhard, D

    2009-05-01

    These guidelines on the management of HSV, VZV and EBV infection in patients with hematological malignancies and after SCT were prepared by the European Conference on Infections in Leukemia following a predefined methodology. A PubMed search was conducted using the appropriate key words to identify studies pertinent to management of HSV, VZV and EBV infections. References of relevant articles and abstracts from recent hematology and SCT scientific meetings were also reviewed. Prospective and retrospective studies identified from the data sources were evaluated, and all data deemed relevant were included in this analysis. The clinical and scientific background was described and discussed, and the quality of evidence and level of recommendation were graded according to the Centers for Disease Control criteria. PMID:19043458

  19. Effect of cell-derived growth factors and cytokines on the clonal outgrowth of EBV-infected B cells and established lymphoblastoid cell lines.

    PubMed

    Ifversen, P; Zhang, X M; Ohlin, M; Zeuthen, J; Borrebaeck, C A

    1993-07-01

    Epstein-Barr virus (EBV) is a potent inducer of polyclonal B lymphocyte proliferation and is widely used as a tool for the establishment of B cell lines producing human monoclonal antibodies. However, because of low transformability, low clonability, and the inherent instability of EBV-infected B cells, valuable antibody-producing B cells are often lost during this procedure. We have here examined various cell-derived cytokines for their ability to enhance both the cellular outgrowth of newly infected B cells and the clonability of infected B cells and lymphoblastoid cell lines. Our results show that the murine thymoma cell line EL-4 is superior to peripheral blood mononuclear cells in both cellular outgrowth and cloning experiments, whereas monocyte-derived factors and monocyte cell lines were less capable than peripheral blood mononuclear cells in enhancing cellular outgrowth and cloning. Furthermore, the human T cell hybridoma cell line MP6 that secretes a B cell growth and differentiation factor, recently identified as an isoform of thioredoxin, is also capable of stimulating EBV-infected B cells and lymphoblastoid cell lines. Co-cultivation of EBV-infected B cells with MP6 cells significantly enhanced the cloning efficiency at the 1 cell/well level. The present results also suggest that one potential role of the MP6-derived thioredoxin could be the up regulation of IL-6 receptor expression in EBV-infected B cells. PMID:8395232

  20. [Lifecycles of EBV and cancer].

    PubMed

    Murata, Takayuki

    2014-01-01

    Epstein-Barr virus (EBV) is a member of gamma-herpesvirus, which can cause various types of tumor. Coexisting with the host for a long period of time, it has evolved unique and sophisticated strategy for survival by taking complicated, tactical modes of infection. Such modes include latent and lytic infections, and latent state is further categorized into four types. Differences and transitions in such lifestyles are significantly associated not only with virus amplification, but also with pathology and advancement of the disorders. I here review oncogenesis and pathogenesis of EBV-related disorders, especially focusing on our recent results on the modes of EBV infection. PMID:25765985

  1. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.

    PubMed

    Otto, Carolin; Hofmann, Jörg; Ruprecht, Klemens

    2016-06-01

    Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our

  2. Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity: implications for possible immune adjuvant therapy.

    PubMed

    Strong, Michael J; Xu, Guorong; Coco, Joseph; Baribault, Carl; Vinay, Dass S; Lacey, Michelle R; Strong, Amy L; Lehman, Teresa A; Seddon, Michael B; Lin, Zhen; Concha, Monica; Baddoo, Melody; Ferris, Marybeth; Swan, Kenneth F; Sullivan, Deborah E; Burow, Matthew E; Taylor, Christopher M; Flemington, Erik K

    2013-01-01

    Epstein-Barr virus (EBV) is associated with roughly 10% of gastric carcinomas worldwide (EBVaGC). Although previous investigations provide a strong link between EBV and gastric carcinomas, these studies were performed using selected EBV gene probes. Using a cohort of gastric carcinoma RNA-seq data sets from The Cancer Genome Atlas (TCGA), we performed a quantitative and global assessment of EBV gene expression in gastric carcinomas and assessed EBV associated cellular pathway alterations. EBV transcripts were detected in 17% of samples but these samples varied significantly in EBV coverage depth. In four samples with the highest EBV coverage (hiEBVaGC - high EBV associated gastric carcinoma), transcripts from the BamHI A region comprised the majority of EBV reads. Expression of LMP2, and to a lesser extent, LMP1 were also observed as was evidence of abortive lytic replication. Analysis of cellular gene expression indicated significant immune cell infiltration and a predominant IFNG response in samples expressing high levels of EBV transcripts relative to samples expressing low or no EBV transcripts. Despite the apparent immune cell infiltration, high levels of the cytotoxic T-cell (CTL) and natural killer (NK) cell inhibitor, IDO1, was observed in the hiEBVaGCs samples suggesting an active tolerance inducing pathway in this subgroup. These results were confirmed in a separate cohort of 21 Vietnamese gastric carcinoma samples using qRT-PCR and on tissue samples using in situ hybridization and immunohistochemistry. Lastly, a panel of tumor suppressors and candidate oncogenes were expressed at lower levels in hiEBVaGC versus EBV-low and EBV-negative gastric cancers suggesting the direct regulation of tumor pathways by EBV. PMID:23671415

  3. Theodore E. Woodward Award: development of novel, EBV-targeted therapies for EBV-positive tumors.

    PubMed

    Kenney, Shannon

    2006-01-01

    The near universal presence of EBV in certain tumors suggests that new EBV-based therapies could be developed for these malignancies. We have explored one EBV-based therapy that involves the purposeful induction of lytic EBV infection in tumors. Induction of lytic EBV infection in tumors activates expression of EBV-encoded kinases that convert the prodrug, ganciclovir, to its active cytotoxic form. In mouse models for EBV-positive tumors, the combination of lytic-inducing chemotherapy and ganciclovir is much more effective than either agent alone for treating tumors. Another potential EBV-based target is the cellular protein, CD70. EBV-positive tumors commonly express CD70, while CD70 expression in normal cells is restricted to a few highly activated B cells and T cells. Anti-CD70 monoclonal antibody inhibits the growth of CD70-positive (but not CD70-negative) Burkitt's lymphomas in SCID mice. Finally, while completely lytic EBV infection is clearly incompatible with tumor cell growth, we recently discovered that small numbers of lytically-infected cells actually promote the growth of EBV-immortalized lymphocytes in SCID mice, through the release of paracrine growth factors as well as angiogenic factors. Thus, agents that prevent the earliest stage of lytic EBV infection (such as fatty acid synthase inhibitors), rather than the later stage of viral replication, might also be useful in the treatment of early-stage EBV-positive tumors. PMID:18528464

  4. Theodore E. Woodward Award: Development of Novel, EBV-Targeted Therapies for EBV-Positive Tumors

    PubMed Central

    Kenney, Shannon

    2006-01-01

    The near universal presence of EBV in certain tumors suggests that new EBV-based therapies could be developed for these malignancies. We have explored one EBV-based therapy that involves the purposeful induction of lytic EBV infection in tumors. Induction of lytic EBV infection in tumors activates expression of EBV-encoded kinases that convert the prodrug, ganciclovir, to its active cytotoxic form. In mouse models for EBV-positive tumors, the combination of lytic-inducing chemotherapy and ganciclovir is much more effective than either agent alone for treating tumors. Another potential EBV-based target is the cellular protein, CD70. EBV-positive tumors commonly express CD70, while CD70 expression in normal cells is restricted to a few highly activated B cells and T cells. Anti-CD70 monoclonal antibody inhibits the growth of CD70-positive (but not CD70-negative) Burkitt’s lymphomas in SCID mice. Finally, while completely lytic EBV infection is clearly incompatible with tumor cell growth, we recently discovered that small numbers of lytically-infected cells actually promote the growth of EBV-immortalized lymphocytes in SCID mice, through the release of paracrine growth factors as well as angiogenic factors. Thus, agents that prevent the earliest stage of lytic EBV infection (such as fatty acid synthase inhibitors), rather than the later stage of viral replication, might also be useful in the treatment of early-stage EBV-positive tumors. PMID:18528464

  5. Acute acalculous cholecystitis in a Lebanese girl with primary Epstein-Barr viral infection.

    PubMed

    Majdalani, Marianne; Milad, Nadine; Sahli, Zeyad; Rizk, Sarah

    2016-01-01

    Acute acalculous cholecystitis (AAC) constitutes 5-10% of all cases of cholecystitis in adults, and is even less common in children. The recent literature has described an association between primary Epstein-Barr virus (EBV) infection and AAC, however, it still remains an uncommon presentation of the infection. Most authors advise that the management of AAC in patients with primary EBV infection should be supportive, since the use of antibiotics does not seem to alter the severity or prognosis of the illness. Furthermore, surgical intervention has not been described as necessary or indicated in the management of uncomplicated AAC associated with EBV infection. We report a case of a 16-year-old Lebanese girl with AAC associated with primary EBV infection. She presented to the emergency department, with high-grade fever, fatigue, vomiting and abdominal pain. Liver enzymes were elevated with a cholestatic pattern, and imaging confirmed the diagnosis of AAC. She was admitted to the regular floor, and initial management was conservative. Owing to persistence of fever, antibiotics were initiated on day 3 of admission. She had a smooth clinical course and was discharged home after a total of 9 days, with no complications. PMID:27090538

  6. Fusion of EBV with the surface of receptor-negative human hepatoma cell line Li7A permits virus penetration and infection.

    PubMed

    Lisi, A; Pozzi, D; Carloni, G; Da Villa, G; Iacovacci, S; Valli, M B; Grimaldi, S

    1995-01-01

    Our preliminary data suggest that Epstein-Barr virus (EBV) is able to bind to and fuse with the surface membranes of hepatoma cell line Li7A. In order to obtain further evidence, we utilized the relief of rhodamine fluorescence to monitor whether fusion would also take place when Li7A cells were exposed to experimental conditions such as neutral or low pH. It is well known that for some viruses, protonation in the endosomal compartment is needed to trigger the fusion. We show, furthermore, that the rate and extent of fusion are not affected by pretreatment of the cells with agents known to elevate the lysosomal and ensodomal pH, such as chloroquine or NH4Cl (lysosomotropic agent). By indirect immunofluorescence assay, in addition, we confirmed the binding of the EBV to the Li7A cell surface membrane. We attempted finally to correlate the above processes with successful infection of Li7A cells by EBV detected using the polymerase chain reaction technique. In spite of the apparent lack of viral receptor CD21, these nonlymphoid cells appeared susceptible to EBV penetration and infection through fusion with the plasma membrane at the surface of the cells. PMID:8539493

  7. Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Gibault-Genty, Geraldine; Khau, David; Monnier, Sebastien; Greder-Belan, Alix

    2012-01-01

    We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Still's disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed. PMID:23166163

  8. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    ... by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact Urine Most people come into contact with ... with another person. You should avoid kissing and sexual contact with an infected person. The virus may ...

  9. Proof for EBV's Sustaining Role in Burkitt's Lymphomas

    PubMed Central

    Vereide, David; Sugden, Bill

    2009-01-01

    We have found that not all Epstein-Barr viral (EBV) plasmids are duplicated each cell cycle. This inefficiency is intrinsic to EBV's mechanism of DNA synthesis in latently infected cells and necessarily leads to a loss of EBV plasmids from proliferating cells. If EBV provides its host cells advantages that allow those cells that retain EBV to outgrow those that lose it, then such proliferating populations will be EBV-positive. EBV-associated human tumors are EBV-positive. Thus the presence of EBV plasmids in most cells of a tumor demonstrates that EBV sustains these tumors in vivo. The virus can provide multiple selective advantages to tumor cells, including promoting cell proliferation and inhibiting cell death. In the case of Burkitt's lymphomas (BL), most current evidence indicates that the tumor requires the virus minimally to block apoptosis. PMID:19628040

  10. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  11. Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection.

    PubMed

    Saeed, Muhammad; Dabbagh, Omar; Al-Muhaizae, Muhammad; Dhalaan, Hesham; Chedrawi, Aziza

    2014-11-01

    Epstein-Barr Virus (EBV) causes a broad spectrum of disease in humans with several clinical syndromes and is ubiquitous, infecting more than 95% of the world's population. Central Nervous System (CNS) disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. Systemic viral illness in children and complications are rare, but may occur. In few cases, it is associated with a variety of CNS and hematological complications like acute disseminated encephalomyelitis, transverse myelitis, neuropsychiatric syndrome, GBS, autoimmune thrombocytopenia and hemolytic anemia and they usually respond to immunotherapy. We report previously healthy boy, who presented with left sided weakness, headache and thrombocytopenia following EBV infection. The thrombocytopenia was resistant to intravenous immunoglobulin and methylprednisolone but responded well to Rituximab. PMID:25518779

  12. EBV associated lymphomas in 2008 WHO classification.

    PubMed

    Zhang, Tiantian; Fu, Qianqian; Gao, Dalin; Ge, Liyan; Sun, Lin; Zhai, Qiongli

    2014-02-01

    Epstein-Barr virus (EBV) is a ubiquitous γ-herpes virus that asymptomatically infects more than 90% of the world's population. The exact mechanism of EBV in oncogenesis is an area of active debate. However, EBV has been implicated in the pathogenesis of several kinds of lymphomas and lymphoproliferative disorders, including B-, T- and NK-cell derived. Subsequent studies have proven that the EBV gene expression product plays an activating and/or promoting role on lymphomagenesis, and paves the way for novel cellular therapies of EBV-associated lymphomas. This review concentrates on the pathology, morphology, treatment and prognosis of EBV-associated lymphomas in the 2008 WHO classification of tumors of hematopoietic and lymphoma tissues. PMID:24355441

  13. EBV Lymphoproliferative Disease after Hematopoietic Stem Cell Transplant

    PubMed Central

    Rouce, Rayne H; Louis, Chrystal U; Heslop, Helen E

    2014-01-01

    PURPOSE OF REVIEW EBV reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (SCT). Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD. RECENT FINDINGS During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped to identify high-risk patients and to diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte (EBV-CTL) response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third party EBV-CTLs. Defining criteria for preemptive therapy and remains a challenge. SUMMARY EBV reactivation is a significant complication after SCT. Continued improvements in risk-stratification and treatment options are required to improve the morbidity and mortality caused by EBV associated diseases. Current approaches use Rituximab to deplete B cells or adoptive transfer of EBV-CTL to reconstitute immunity. The availability of rapid EBV specific T cell products offers the possibility of improved outcomes. PMID:25159713

  14. Retention of anergy and inhibition of antibody responses during acute γ herpesvirus 68 infection.

    PubMed

    Getahun, Andrew; Smith, Mia J; Kogut, Igor; van Dyk, Linda F; Cambier, John C

    2012-09-15

    The majority of the human population becomes infected early in life by the gammaherpesvirus EBV. Some findings suggest that there is an association between EBV infection and the appearance of pathogenic Abs found in lupus. Gammaherpesvirus 68 infection of adult mice (an EBV model) was shown to induce polyclonal B cell activation and hypergammaglobulinemia, as well as increased production of autoantibodies. In this study, we explored the possibility that this breach of tolerance reflects loss of B cell anergy. Our findings show that, although anergic B cells transiently acquire an activated phenotype early during infection, they do not become responsive to autoantigen, as measured by the ability to mobilize Ca2+ following AgR cross-linking or mount Ab responses following immunization. Indeed, naive B cells also acquire an activated phenotype during acute infection but are unable to mount Ab responses to either T cell-dependent or T cell-independent Ags. In acutely infected animals, Ag stimulation leads to upregulation of costimulatory molecules and relocalization of Ag-specific B cells to the B-T cell border; however, these cells do not proliferate or differentiate into Ab-secreting cells. Adoptive-transfer experiments show that the suppressed state is reversible and is dictated by the environment in the infected host. Finally, B cells in infected mice deficient of CD4+ T cells are not suppressed, suggesting a role for CD4+ T cells in enforcing unresponsiveness. Thus, rather than promoting loss of tolerance, gammaherpesvirus 68 infection induces an immunosuppressed state, reminiscent of compensatory anti-inflammatory response syndrome. PMID:22904300

  15. Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

    PubMed

    Zhang, Shuo; Feng, Juan; Shi, Yifang

    2016-01-01

    Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. PMID:26600186

  16. EBV-associated lymphomas in adults

    PubMed Central

    Roschewski, Mark

    2012-01-01

    Epstein-Barr virus (EBV) is a ubiquitous γ-herpes virus that infects most people but results in life-threatening diseases in only a small subset. Persons who are unable to maintain the virus in its latent state can develop uncontrolled EBV-driven lymphoproliferative disorders and lymphomas. EBV-associated lymphomas are well-characterized in patients with known defects in cellular immunity as occurs post-transplantation or HIV/AIDS but are increasingly recognized in patients without overt immunodeficiencies. Improved understanding of the biology of these lymphomas and the role EBV plays in lymphomagenesis offers the opportunity for improved therapies targeted at important signaling pathways and immunotherapy specific against EBV viral antigens. PMID:22409825

  17. The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

    PubMed

    Kanakry, Jennifer A; Hegde, Aparna M; Durand, Christine M; Massie, Allan B; Greer, Amy E; Ambinder, Richard F; Valsamakis, Alexandra

    2016-04-21

    Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV(+)disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV(+)disease. In patients with active, systemic EBV(+)diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV(+)disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV(+)lymphoma from EBV(+)lymphoma in remission and EBV(-)lymphoma, and also distinguished untreated, EBV(+)posttransplantation lymphoproliferative disorder (PTLD) from EBV(+)PTLD in remission and EBV(-)PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV(+)diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV(+)disease than PBMCs. PMID:26744460

  18. Transcriptional activation by EBV nuclear antigen 1 is essential for the expression of EBV's transforming genes

    PubMed Central

    Altmann, Markus; Pich, Dagmar; Ruiss, Romana; Wang, Jindong; Sugden, Bill; Hammerschmidt, Wolfgang

    2006-01-01

    EBV is a paradigm for human tumor viruses because, although it infects most people benignly, it also can cause a variety of cancers. Both in vivo and in vitro, EBV infects B lymphocytes in G0, induces them to become blasts, and can maintain their proliferation in cell culture or in vivo as tumors. How EBV succeeds in these contrasting cellular environments in expressing its genes that control the host has not been explained. We have genetically dissected the EBV nuclear antigen 1 (EBNA1) gene that is required for replication of the viral genome, to elucidate its possible role in the transcription of viral genes. Strikingly, EBNA1 is essential to drive transcription of EBV's transforming genes after infection of primary B lymphocytes. PMID:16966603

  19. EBNA3C Directs Recruitment of RBPJ (CBF1) to Chromatin during the Process of Gene Repression in EBV Infected B Cells

    PubMed Central

    Kalchschmidt, Jens S.; Gillman, Adam C. T.; Paschos, Kostas; Bazot, Quentin; Kempkes, Bettina; Allday, Martin J.

    2016-01-01

    It is well established that Epstein-Barr virus nuclear antigen 3C (EBNA3C) can act as a potent repressor of gene expression, but little is known about the sequence of events occurring during the repression process. To explore further the role of EBNA3C in gene repression–particularly in relation to histone modifications and cell factors involved–the three host genes previously reported as most robustly repressed by EBNA3C were investigated. COBLL1, a gene of unknown function, is regulated by EBNA3C alone and the two co-regulated disintegrin/metalloproteases, ADAM28 and ADAMDEC1 have been described previously as targets of both EBNA3A and EBNA3C. For the first time, EBNA3C was here shown to be the main regulator of all three genes early after infection of primary B cells. Using various EBV-recombinants, repression over orders of magnitude was seen only when EBNA3C was expressed. Unexpectedly, full repression was not achieved until 30 days after infection. This was accurately reproduced in established LCLs carrying EBV-recombinants conditional for EBNA3C function, demonstrating the utility of the conditional system to replicate events early after infection. Using this system, detailed chromatin immunoprecipitation analysis revealed that the initial repression was associated with loss of activation-associated histone modifications (H3K9ac, H3K27ac and H3K4me3) and was independent of recruitment of polycomb proteins and deposition of the repressive H3K27me3 modification, which were only observed later in repression. Most remarkable, and in contrast to current models of RBPJ in repression, was the observation that this DNA-binding factor accumulated at the EBNA3C-binding sites only when EBNA3C was functional. Transient reporter assays indicated that repression of these genes was dependent on the interaction between EBNA3C and RBPJ. This was confirmed with a novel EBV-recombinant encoding a mutant of EBNA3C unable to bind RBPJ, by showing this virus was incapable of

  20. EBNA3C Directs Recruitment of RBPJ (CBF1) to Chromatin during the Process of Gene Repression in EBV Infected B Cells.

    PubMed

    Kalchschmidt, Jens S; Gillman, Adam C T; Paschos, Kostas; Bazot, Quentin; Kempkes, Bettina; Allday, Martin J

    2016-01-01

    It is well established that Epstein-Barr virus nuclear antigen 3C (EBNA3C) can act as a potent repressor of gene expression, but little is known about the sequence of events occurring during the repression process. To explore further the role of EBNA3C in gene repression-particularly in relation to histone modifications and cell factors involved-the three host genes previously reported as most robustly repressed by EBNA3C were investigated. COBLL1, a gene of unknown function, is regulated by EBNA3C alone and the two co-regulated disintegrin/metalloproteases, ADAM28 and ADAMDEC1 have been described previously as targets of both EBNA3A and EBNA3C. For the first time, EBNA3C was here shown to be the main regulator of all three genes early after infection of primary B cells. Using various EBV-recombinants, repression over orders of magnitude was seen only when EBNA3C was expressed. Unexpectedly, full repression was not achieved until 30 days after infection. This was accurately reproduced in established LCLs carrying EBV-recombinants conditional for EBNA3C function, demonstrating the utility of the conditional system to replicate events early after infection. Using this system, detailed chromatin immunoprecipitation analysis revealed that the initial repression was associated with loss of activation-associated histone modifications (H3K9ac, H3K27ac and H3K4me3) and was independent of recruitment of polycomb proteins and deposition of the repressive H3K27me3 modification, which were only observed later in repression. Most remarkable, and in contrast to current models of RBPJ in repression, was the observation that this DNA-binding factor accumulated at the EBNA3C-binding sites only when EBNA3C was functional. Transient reporter assays indicated that repression of these genes was dependent on the interaction between EBNA3C and RBPJ. This was confirmed with a novel EBV-recombinant encoding a mutant of EBNA3C unable to bind RBPJ, by showing this virus was incapable of

  1. Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

    PubMed

    Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

    2003-10-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious

  2. [PHARMACOLOGICAL CORRECTION OF METABOLIC DISORDERS IN CHILDREN WITH ACUTE EPSTEIN--BARR VIRAL INFECTION].

    PubMed

    Kasymova, E B; Bashkina, O A; Galimzyanov, Kh M; Engibaryan, K Zh; Rodina, L P; Chanpalova, L S; Kovalenko, A L

    2016-01-01

    The study was aimed to investigate the influence of drug reamberin inclusion in the treatment regimen of patients with acute Epstein-Barr virus (EBV) infection on the effectiveness of therapy. Treatment results were analyzed in a group of 70 children aged 4-15 with a diagnosis of moderate to severe EBV infection. By the method of random sampling distribution, patients were divided into two comparable groups of 35 children, which were representative with respect to gender, age, date of admission, and conducted basic therapy. Patients in the control group were treated by the conventional scheme, while the main group received basic therapy with antibacterial drug (according to indication) and symptomatic agents (antipyretics, desensitizing agents, and local antiseptics for the treatment of rotor and nasopharynx) and, in addition, obtained 1.5% reamberin solution intravenously, 10 mL/kg body weight once a day at a rate of 3-4 mL/min (the treatment course did not exceed 3 days). Treatment efficacy was assessed by a decrease in the duration of intoxication symptoms, relief of their clinical manifestations, and normalization of laboratory data (including, in addition to commonly accepted data, the levels of malonic dialdehyde, ferritin, transferrin and catalase before and after treatment).The inclusion of reamberin in the therapy of acute EBV infection in children favors (in comparison to conventional treatment regimen) more pronounced and rapid decrease the intensity of the oxidative process and improves the functioning of the antioxidant system. This was manifested by normalization of immunobiochemical indicators (reduction of malonic dialdehyde and ferritin and increase in the level of catalase) and decrease in the inflammatory response (leukocytosis, ESR, and the number of atypical mononuclear cells in the blood), This resulted in more rapid relief of the clinical manifestations of infection (sore throat, hyperthermia, lymphadenopathy, and hepatomegaly) and shortened

  3. Dengue infection presenting as acute hypokalemic quadriparesis.

    PubMed

    Gupta, N; Garg, A; Chhabra, P

    2014-01-01

    Dengue infection is one of the most common viral hemorrhagic fevers seen in the tropical countries, including India. Its presentation varies from an acute self-resolving febrile illness to life-threatening hemorrhagic shock and multiorgan dysfunction leading to death. Neurological presentations are uncommon and limited to case reports only. Most common neurological manifestations being encephalitis, acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting feature of dengue is extremely rare. Here, we report this case of a 33-year-old female, who presented with hypokalemic quadriparesis and was subsequently diagnosed as dengue infection. PMID:25121379

  4. Expression of EBV-encoded oncogenes and EBV-like virions in multiple canine tumors.

    PubMed

    Chiu, Hung-Chuan; Chow, Kuan-Chih; Fan, Yi-Hsin; Chang, Shih-Chieh; Chiou, Shiow-Her; Chiang, Shu-Fen; Chiou, Che-Hao; Wu, Guo-Hua; Yang, Hsiu-Ching; Ho, Shu-Peng; Chen, Yuh-Kun; Lee, Wei-Cheng; Sun, H Sunny

    2013-04-12

    Epstein-Barr virus (EBV) is a ubiquitous human oncovirus. Previous studies by us and others have indicated that pet dogs frequently encounter EBV or EBV-related viral infection. In this study, we explored whether EBV is involved in canine malignancies in dogs. EBV-specific BamHI W sequence was detected by polymerase chain reaction (PCR) in 10 of 12 canine tumor specimens, including 8 of 10 oral tumors. Using reverse transcription-PCR, gene expressions of latent membrane protein 1 (LMP 1) and BamHI H rightward reading frame 1 (BHRF1) were identified in 8 and 7 of 12 specimens, respectively. A novel LMP1 variant, T0905, was predominant in 5 canine tumor specimens and found to exist in EBV positive human BC-2 cells. Another LMP1 variant, T0902, was similar to human tumor variant JB7. The BHRF1 sequence identified from these canine tumors was identical to that of the B95-8 viral strain. LMP1 protein and EBV-encoded RNA (EBER) were detected by immunohistochemistry and fluorescent in situ hybridization, respectively, in several tumors, particularly in tumor nests of oral amelanotic melanomas. Furthermore, EBV-like virions adopting a herpesvirus egress pathway were detected in a canthal fibroblastic osteosarcoma and an oral amelanotic melanoma. In conclusion, we report the expressions of BHRF1 transcript (a viral anti-apoptotic protein), LMP1 (a viral oncoprotein) transcript and protein, EBER (a viral oncogenic RNA), and EBV-like virions in multiple canine tumors. The identity of BHRF1 and the resemblance of LMP1 variants between canine and human tumors indicate either a close evolutionary relationship between canine and human EBV, or the possibility of zoonotic transmission. PMID:23380461

  5. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation

    PubMed Central

    Doubrovina, Ekaterina; Oflaz-Sozmen, Banu; Prockop, Susan E.; Kernan, Nancy A.; Abramson, Sara; Teruya-Feldstein, Julie; Hedvat, Cyrus; Chou, Joanne F.; Heller, Glenn; Barker, Juliet N.; Boulad, Farid; Castro-Malaspina, Hugo; George, Diane; Jakubowski, Ann; Koehne, Guenther; Papadopoulos, Esperanza B.; Scaradavou, Andromachi; Small, Trudy N.; Khalaf, Ramzi; Young, James W.

    2012-01-01

    We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell transplantation recipients with biopsy-proven EBV-lymphoproliferative disease (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions in 73% and 68% of treated patients including 74% and 72% of patients surviving ≥ 8 days after infusion, respectively. Reversible acute GVHD occurred in recipients of DLIs (17%) but not EBV-CTLs. The probability of complete response was significantly lower among patients with multiorgan involvement. In responders, DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not increase and EBV viremia persisted. Treatment failures were correlated with impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the patient's blood or biopsied tumor or they failed to lyse their targets because they were selectively restricted by HLA alleles not shared by the EBV-LPD. Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to impaired T-cell recognition of tumor-associated viral antigens or their presenting HLA alleles. PMID:22138512

  6. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  7. [Associated infections in acute bronchopulmonary infections in children].

    PubMed

    Lykova, E A; Vorob'ev, A A; Bokovoĭ, A G; Karazhas, N V; Evseeva, L F

    2003-01-01

    A total of 189 children with bacterial complications of the acute respiratory viral infection (ARVI)--primarily with pneumonia and bronchitis--were dynamically examined for typical and atypical pneumotropic causative agents of the infection process (Mycoplasma pneumoniae, Chlamydia spp., Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis carini, and Citomegalovirus). A high frequency rate of the associative infection involving mycoplasmas and pneumocysts was registered (45-50%); it was lower in the cases involving Chlamydias, hemophilic bacteria, pneumococcus, and cytomegalovirus--up to 25-30%. No sharp difference was found between the indices of an infection degree and those of an active clinical infectious process involving the same pneumotropic agent: the biggest difference was observed in Chlamydia infections (9.4%) and the lowest one--in mycoplasma infections (3%). A dynamic comparison of different classes of immunoglobulins revealed that, in acute bronchitis and pneumonias, the Chlamydia and cytomegalovirus infections are, primarily, of the persistent nature; the hemophilic and pneumocystic infections are of a mixed nature; and the pneumococcus one is of the acute nature. The Mycoplasma infection, which is more often encountered in pre-school children, is of the primary type with a trend towards a prolonged clinical course. All pneumonias had a typical clinical course; the clinical picture was compared in 128 patients with the etiological factor (including a description of characteristic symptoms). PMID:12861708

  8. Nominal dysphasia and euphoria caused by EBV encephalitis.

    PubMed

    Carman, Kursat Bora; Yakut, Ayten; Ekici, Arzu; Isikay, Sedat

    2013-01-01

    Encephalitis is an uncommon neurological complication of Ebstein-Barr virus (EBV) infection and usually presents with confusion, decreased level of consciousness, fever, epileptic seizure, emotional instability and chorea. We present a patient with EBV encephalitis, characterised by nominal dysphasia, euphoria and personality changes. PMID:23307455

  9. Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertype-restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T lymphocytes.

    PubMed

    Khanna, R; Burrows, S R; Nicholls, J; Poulsen, L M

    1998-02-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) and latent membrane proteins (LMP) are the only antigens consistently expressed in malignancies such as nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). Since EBNA1 is not recognized by EBV-specific cytotoxic T lymphocytes (CTL), there is increasing interest in the identification of the potential target epitopes within LMP1. Although LMP1-specific CTL have been isolated from seropositive individuals, earlier attempts to identify the peptide epitopes recognized by these T cells have been unsuccessful. In the present report we used a novel protocol to identify CTL epitopes within LMP1 which can be recognized by both polyclonal and clonal CTL. Firstly, a computer-based program was employed to identify the potential HLA-binding peptides within LMP1. Polyclonal CD8+ CTL were then isolated from seropositive donors that recognized the peptide epitopes YLLEMLWRL and YLQQNWWTL from LMP1 in association with HLA A2. Limiting dilution analysis of the memory CTL response revealed that the LMP1-specific CTL response constitutes a minor component of the CTL response in healthy virus carriers. Interestingly, analysis of YLLEMLWRL-specific CTL revealed that these CTL were able to lyse EBV-infected B cells expressing different HLA A2 supertype alleles including A*0201, A*0202, A*0203, A*0204, A*0206, A*6802 and A*6901. These data strongly support the notion that HLA class I supertype-restricted CTL may be of significant use in the development of peptide-based immunotherapeutics against EBV-associated malignancies in different ethnic populations. PMID:9521052

  10. Kocuria kristinae infection associated with acute cholecystitis

    PubMed Central

    Ma, Edmond SK; Wong, Chris LP; Lai, Kristi TW; Chan, Edmond CH; Yam, WC; Chan, Angus CW

    2005-01-01

    Background Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. Case presentation We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Conclusion Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases. PMID:16029488

  11. 18F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma

    PubMed Central

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on 18F-FDG PET/CT mimicked malignant lymphoma. Follow-up 18F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting 18F-FDG PET/CT scans. PMID:27187482

  12. (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma.

    PubMed

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting (18)F-FDG PET/CT scans. PMID:27187482

  13. [Role of tumor-derived secretary small RNAs in EBV related lymphoma].

    PubMed

    Kotani, Ai

    2014-01-01

    EB virus (EBV) is associated with heterogeneous lymphomas. In these lymphomas EBV+ lymphoma cells are embedded in non-neoplastic bystanders: B and T cells, macrophages. Without these bystander cells, the lymphoma cells are incapable of being engrafted in immunodeficient mice. In this context, the bystanders are tumor-supportive "inflammatory niche". Recently, EBV-infected cells produce exosomes that contain EBV specifically encoded miRNAs (EBV-miRNAs). Accordingly, we hypothesized that exosomal EBV-miRNAs might redirect tumor surrounding immune cells from tumor reactive into tumor-supportive "inflammatory niche". The EBV-miRNAs in the exosome secreted from EBV positive lymphoma cells significantly influenced on monocyte/macrophage Mo/Mf in inducing CD69, IL-10, and TNF, suggesting that EBV-miRNAs might polarize Mo/Mf into tumor associated Mf (TAM). EBV-miRNAs were required to develop lymphoproliferative disease (LPD) in vivo mouse model. Moreover, when Mfs were depleted by clodronate liposome, EBV positive tumor cells disappeared. These results suggest that lymphoma-derived secretary EBV-miRNAs regulate Mo/Mf to support the lymphoma survival or development. Most importantly, exosomal EBV-miRNAs derived from the lymphoma cells were transferred to Mf in human EBV+ lymphoma samples, which showed correlation with prognosis. PMID:25765979

  14. [The Most Common Acute Gastrointestinal Infections].

    PubMed

    Greuter, Thomas; Magdeburg, Bernhard

    2015-10-14

    Acute gastrointestinal infections and diarrhea with vomiting as its main presentation are a frequently encountered entity in an outpatient setting. Due to a mostly self-limiting disease course a diagnostic work-up is often futile. Viral infections caused by Noro- or Rotavirus are most frequent, while bacterial infections are second line due to high hygienic standards in developed countries. In an inpatient setting and after a precedent antibiotic treatment one should think of clostridium difficile. Traveler’s diarrhea represents a special case, with most of the cases caused by enterovirulent E. coli. In this mini review we describe the most important pathogens in detail. PMID:26463905

  15. Infectivity of pestivirus following persistence of acute infection.

    PubMed

    Collins, Margaret E; Heaney, Judith; Thomas, Carole J; Brownlie, Joe

    2009-09-18

    Bovine viral diarrhoea virus (BVDV) is an endemic pathogen worldwide and eradication strategies focus on the identification and removal of persistently infected (PI) animals arising after in utero infection. Despite this, acute infections with BVDV can persist for months or years after the removal of the PI source despite repeated screening for PIs and tight biosecurity measures. Recent evidence for a prolonged duration of viraemia in the testicles of bulls following acute BVDV infection suggests the possibility of a form of chronic persistence that may more closely resemble the persistence strategies of hepatitis C virus (HCV). To investigate the potential for virus transmission from infected and recovered cattle to virus naïve hosts we established an acute infection of 5 BVDV-naïve calves and monitored animals over 129 days. Infectious BVDV was detected in white blood cells between days 3 and 7 post-challenge. The animals seroconverted by day 21 post-infection and subsequently were apparently immune and free from infectious virus and viral antigen. Animals were further monitored and purified white blood cells were stimulated in vitro with phytohaemagglutinin A (PHA) during which time BVDV RNA was detected intermittently. Ninety-eight days following challenge, blood was transferred from these apparently virus-free and actively immune animals to a further group of 5 BVDV-naïve calves and transmission of infection was achieved. This indicates that BVDV-infected, recovered and immune animals have the potential to remain infectious for BVDV-naïve cohorts for longer than previously demonstrated. PMID:19443139

  16. Pulmonary embolism and acute cytomegalovirus infection in an immunocompetent patient.

    PubMed

    Del Borgo, Cosmo; Gianfreda, Romina; Belvisi, Valeria; Citton, Rita; Soscia, Fabrizio; Notarianni, Ermanno; Tieghi, Tiziana; Mastroianni, Claudio Maria

    2010-12-01

    A case of an immunocompetent man with acute CMV infection associated with a pulmonary embolism is described. Acute CMV infection could be a risk factor for developing thromboembolism. Pulmonary embolism should be included in differential diagnosis in patients with acute CMV infections and pulmonary opacities. PMID:21196823

  17. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  18. Swaddling and acute respiratory infections.

    PubMed

    Yurdakok, K; Yavuz, T; Taylor, C E

    1990-07-01

    In Turkey and China the ancient practice of swaddling is still commonly practiced. Both countries have extremely high rates of pneumonia, especially during the neonatal period. Preliminary evidence on the possibility that swaddling may interfere with normal respiratory function and thereby predispose to pneumonia was gathered in a teaching health center in Ankara. Babies who had been swaddled for at least three months were four times more likely to have developed pneumonia (confirmed radiologically) and upper respiratory infections than babies who were unswaddled. These preliminary findings were highly significant and are being followed up by further studies. PMID:2356917

  19. Inhibition of autophagy in EBV-positive Burkitt's lymphoma cells enhances EBV lytic genes expression and replication.

    PubMed

    De Leo, A; Colavita, F; Ciccosanti, F; Fimia, G M; Lieberman, P M; Mattia, E

    2015-01-01

    Autophagy, an important degradation system involved in maintaining cellular homeostasis, serves also to eliminate pathogens and process their fragments for presentation to the immune system. Several viruses have been shown to interact with the host autophagic machinery to suppress or make use of this cellular catabolic pathway to enhance their survival and replication. Epstein Barr virus (EBV) is a γ-herpes virus associated with a number of malignancies of epithelial and lymphoid origin in which establishes a predominantly latent infection. Latent EBV can periodically reactivate to produce infectious particles that allow the virus to spread and can lead to the death of the infected cell. In this study, we analyzed the relationship between autophagy and EBV reactivation in Burkitt's lymphoma cells. By monitoring autophagy markers and EBV lytic genes expression, we demonstrate that autophagy is enhanced in the early phases of EBV lytic activation but decreases thereafter concomitantly with increased levels of EBV lytic proteins. In a cell line defective for late antigens expression, we found an inverse correlation between EBV early antigens expression and autophagosomes formation, suggesting that early after activation, the virus is able to suppress autophagy. We report here for the first time that inhibition of autophagy by Bafilomycin A1 or shRNA knockdown of Beclin1 gene, highly incremented EBV lytic genes expression as well as intracellular viral DNA and viral progeny yield. Taken together, these findings indicate that EBV activation induces the autophagic response, which is soon inhibited by the expression of EBV early lytic products. Moreover, our findings open the possibility that pharmacological inhibitors of autophagy may be used to enhance oncolytic viral therapy of EBV-related lymphomas. PMID:26335716

  20. Inhibition of autophagy in EBV-positive Burkitt's lymphoma cells enhances EBV lytic genes expression and replication

    PubMed Central

    De Leo, A; Colavita, F; Ciccosanti, F; Fimia, G M; Lieberman, P M; Mattia, E

    2015-01-01

    Autophagy, an important degradation system involved in maintaining cellular homeostasis, serves also to eliminate pathogens and process their fragments for presentation to the immune system. Several viruses have been shown to interact with the host autophagic machinery to suppress or make use of this cellular catabolic pathway to enhance their survival and replication. Epstein Barr virus (EBV) is a γ-herpes virus associated with a number of malignancies of epithelial and lymphoid origin in which establishes a predominantly latent infection. Latent EBV can periodically reactivate to produce infectious particles that allow the virus to spread and can lead to the death of the infected cell. In this study, we analyzed the relationship between autophagy and EBV reactivation in Burkitt's lymphoma cells. By monitoring autophagy markers and EBV lytic genes expression, we demonstrate that autophagy is enhanced in the early phases of EBV lytic activation but decreases thereafter concomitantly with increased levels of EBV lytic proteins. In a cell line defective for late antigens expression, we found an inverse correlation between EBV early antigens expression and autophagosomes formation, suggesting that early after activation, the virus is able to suppress autophagy. We report here for the first time that inhibition of autophagy by Bafilomycin A1 or shRNA knockdown of Beclin1 gene, highly incremented EBV lytic genes expression as well as intracellular viral DNA and viral progeny yield. Taken together, these findings indicate that EBV activation induces the autophagic response, which is soon inhibited by the expression of EBV early lytic products. Moreover, our findings open the possibility that pharmacological inhibitors of autophagy may be used to enhance oncolytic viral therapy of EBV-related lymphomas. PMID:26335716

  1. Innate Immune Recognition of EBV.

    PubMed

    Lünemann, Anna; Rowe, Martin; Nadal, David

    2015-01-01

    The ability of Epstein-Barr virus (EBV) to establish latency despite specific immune responses and to successfully persist lifelong in the human host shows that EBV has developed powerful strategies and mechanisms to exploit, evade, abolish, or downsize otherwise effective immune responses to ensure its own survival. This chapter focuses on current knowledge on innate immune responses against EBV and its evasion strategies for own benefit and summarizes the questions that remain to be tackled. Innate immune reactions against EBV originate both from the main target cells of EBV and from nontarget cells, which are elements of the innate immune system. Thus, we structured our review accordingly but with a particular focus on the innate recognition of EBV in its two stages in its life cycle, latent state and lytic replication. Specifically, we discuss (I) innate sensing and resulting innate immune responses against EBV by its main target cells, focusing on (i) EBV transmission between epithelial cells and B cells and their life cycle stages; and (ii) elements of innate immunity in EBV's target cells. Further, we debate (II) the innate recognition and resulting innate immune responses against EBV by cells other than the main target cells, focusing on (iii) myeloid cells: dendritic cells, monocytes, macrophages, and neutrophil granulocytes; and (iv) natural killer cells. Finally, we address (III) how EBV counteracts or exploits innate immunity in its latent and lytic life cycle stages, concentrating on (v) TLRs; (vi) EBERs; and (vii) microRNAs. PMID:26428378

  2. Associations between Burkitt Lymphoma among Children in Malawi and Infection with HIV, EBV and Malaria: Results from a Case-Control Study

    PubMed Central

    Mutalima, Nora; Molyneux, Elizabeth; Jaffe, Harold; Kamiza, Steve; Borgstein, Eric; Mkandawire, Nyengo; Liomba, George; Batumba, Mkume; Lagos, Dimitrios; Gratrix, Fiona; Boshoff, Chris; Casabonne, Delphine; Carpenter, Lucy M.; Newton, Robert

    2008-01-01

    Background Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) is not clear. Methodology/Principal Findings We conducted a case-control study of Burkitt lymphoma among children (aged ≤15 years) admitted to the pediatric oncology unit in Blantyre, Malawi between July 2005 and July 2006. Cases were 148 children diagnosed with Burkitt lymphoma and controls were 104 children admitted with non-malignant conditions or cancers other than hematological malignancies and Kaposi sarcoma. Interviews were conducted and serological samples tested for antibodies against HIV, EBV and malaria. Odds ratios for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, and residential district. Cases had a mean age of 7.1 years and 60% were male. Cases were more likely than controls to be HIV positive (Odds ratio (OR))  = 12.4, 95% Confidence Interval (CI) 1.3 to 116.2, p = 0.03). ORs for Burkitt lymphoma increased with increasing antibody titers against EBV (p = 0.001) and malaria (p = 0.01). Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 13.2; 95% CI 3.8 to 46.6; p = 0.001). Reported use of mosquito nets was associated with a lower risk of Burkitt lymphoma (OR =  0.2, 95% CI, 0.03 to 0.9, p = 0.04). Conclusions Our findings support prior evidence that EBV and malaria act jointly in the pathogenesis of Burkitt lymphoma, suggesting that malaria prevention may decrease the risk of Burkitt lymphoma. HIV may also play a role in the etiology of this childhood tumor. PMID:18560562

  3. EBV latency types adopt alternative chromatin conformations.

    PubMed

    Tempera, Italo; Klichinsky, Michael; Lieberman, Paul M

    2011-07-01

    Epstein-Barr Virus (EBV) can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C) assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp) or type III (Cp) gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer. PMID:21829357

  4. A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult.

    PubMed

    Singh, Sukhchain; Khosla, Pam

    2016-01-01

    Epstein-Barr virus (EBV) is a common infection that affects 95% of adults worldwide at some point during life. It is usually asymptomatic or causes a self-limiting clinical syndrome known as infectious mononucleosis. It rarely causes complications. Here, we present a case of a healthy 21-year-old female college student who suffered from severe pancreatitis and life-threatening autoimmune hemolytic anemia in association with EBV infection, and we also discuss the common presentation of EBV infection and the diagnosis and treatment of simple and complicated EBV infection. PMID:26190854

  5. Management of infection in acute pancreatitis.

    PubMed

    Hartwig, Werner; Werner, Jens; Uhl, Waldemar; Büchler, Markus W

    2002-01-01

    The clinical course of acute pancreatitis varies from a mild, transitory illness to a severe, rapidly fatal disease. In about 80% to 90% of cases pancreatitis presents as a mild, self-limiting disease with low morbidity and mortality. Unlike mild pancreatitis, necrotizing pancreatitis develops in about 15% of patients, with infection of pancreatic and peripancreatic necrosis representing the single most important risk factor for a fatal outcome. Infection of pancreatic necrosis in the natural course develops in the second and third week after onset of the disease and is reported in 40% to 70% of patients with necrotizing pancreatitis. Just recently, prevention of infection by prophylactic antibiotic treatment and assessment of the infection status of pancreatic necrosis by fine-needle aspiration have been established in the management of severe pancreatitis. Because medical treatment alone will result in a mortality rate of almost 100% in patients with signs of local and systemic septic complications, patients with infected necrosis must undergo surgical intervention, which consists of an organ-preserving necrosectomy combined with a postoperative closed lavage concept that maximizes further evacuation of infected debris and exudate. However, intensive care treatment, including prophylactic antibiotics, reduces the infection rate and delays the need for surgery in most patients until the third or fourth week after the onset of symptoms. At that time, debridement of necrosis is technically easier to perform, due to better demarcation between viable and necrotic tissue compared with necrosectomy earlier in the disease. In contrast, surgery is rarely needed in the presence of sterile pancreatic necrosis. In those patients the conservative approach is supported by the present data. PMID:12483263

  6. Acute encephalitis as initial presentation of primary HIV infection.

    PubMed

    Nzwalo, Hipólito; Añón, Rosário Pazos; Àguas, Maria João

    2012-01-01

    Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis. PMID:22761210

  7. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  8. New strategies and patent therapeutics in EBV-associated diseases.

    PubMed

    Villegas, E; Santiago, O; Sorlózano, A; Gutierrez, J

    2010-09-01

    Epstein-Barr virus (EBV) is a virus present all throughout the world that causes infectious mononucleosis (IM) and is highly associated with certain malignancies. This study is a review of current knowledge concerning the pathogenic mechanisms of EBV in tumor and auto-immune diseases and the different new strategies to treat EBV associated pathologies. Phenomena surrounding the proliferation and immortalization of B lymphocytes, the mechanisms of immune escape and the role of CD8+ and CD4+ T cells in the infection by EBV are explained. An analysis is made of the role of EBV proteins during the biological events that take place in primary infection, persistent chronic infection together with an update of the approaches of novel patented therapeutics. Currently there is no vaccine protecting against EBV-associated disorders and no treatment that may inhibit or eliminate their progression. Thus, it is crucial to obtain additional information on the function and importance of genes that play a role on the development of those diseases with which it is associated, as well as on the humoral and cellular immune processes involved in them. PMID:21034415

  9. Epstein-Barr Virus (EBV) DNA in plasma is not encapsidated in patients with EBV-related malignancies.

    PubMed

    Ryan, Julie L; Fan, Hongxin; Swinnen, Lode J; Schichman, Steven A; Raab-Traub, Nancy; Covington, Mary; Elmore, Sandra; Gulley, Margaret L

    2004-06-01

    Epstein-Barr Virus (EBV), a ubiquitous gamma herpes virus, infects more than 95% of the human population before adulthood. Life-long persistence, usually without adverse health consequences, relies on a balance between viral latency, viral replication, and host immune response. Patients with EBV-related disease often have high levels of EBV DNA in their plasma. This study addresses whether this circulating, cell-free EBV DNA is encapsidated in virions or exists as naked genomes. First, an assay was developed, combining DNase I and quantitative real-time PCR, to discriminate encapsidated from naked EBV DNA. EBV DNA was almost always naked in the plasma of AIDS-related lymphoma patients (n = 11) and immunosuppressed/posttransplantation patients (n = 8). In contrast, infectious mononucleosis patients (n = 30) often had a mixture of encapsidated and naked EBV DNA. These findings may be important in understanding how viral load relates to disease status and in predicting response to nucleoside analogs and other antiviral therapies. PMID:15167006

  10. Methylation status and AP1 elements are involved in EBV-mediated miR-155 expression in EBV positive lymphoma cells.

    PubMed

    Yin, Qinyan; Wang, Xia; Roberts, Claire; Flemington, Erik K; Lasky, Joseph A

    2016-07-01

    The relationship between Epstein Barr Virus (EBV) and miR-155 is well established. EBV infection induces miR-155 expression, which is expressed at higher levels in EBV latency type III cells compared to EBV latency type I cells. However, the mechanism by which EBV latency genes activate miR-155 expression is still unclear. Here we present data showing that DNA methylation regulates miR-155 expression. We also provide evidence that the AP1 signaling pathway is involved in EBV-mediated miR-155 activation, and that Bay11 influences signaling of the miR-155 promoter AP1 element. Lastly, we show that LMP2A, LMP1 and EBNAs cannot activate miR-155 expression alone, indicating that the regulation of miR-155 by EBV is dependent on more than one EBV gene or cell signaling pathway. We conclude that the regulation of miR-155 in EBV-positive cells occurs through multiple cell signaling processes involving EBV-mediated chromatin remodeling, cell signaling regulation and transcription factor activation. PMID:27110708

  11. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection. PMID:26310309

  12. Helicobacter pylori infection and acute myocardial infarction.

    PubMed

    Nakić, Dario; Vcev, Aleksandar; Jović, Albino; Patrk, Jogen; Zekanović, Drazen; Klarin, Ivo; Ivanac, Kresimir; Mrden, Anamarija; Balen, Sanja

    2011-09-01

    The aim of this investigation was to determine whether H. pylori infection is an independent risk factor for acute myocardial infarction (AMI), determine is there a link between H. pylori infection and severity of disease. In this prospective, single centre study, were enrolled 100 patients with AMI and control group was consisted 93 healthy individuals. The results of this study showed no difference between H. pylori seropositivity distribution in the investigate and control group (29 vs. 26 %) and there was no significant difference on the severity of the disease. There was significant association in the patients with three and more risk factors, where the patients with lower blood pressure (124.4/77.4 vs. 145.9/87.7 mmHg) and better controlled diabetes (HbA1c 6.1% vs. 6.9%) had greater risk for AMI if they are H. pylori seropositive. The large multicentric trials would be needed to define a precise role of H. pylori infection on the developement of AMI. PMID:22053556

  13. EBV and HIV-Related Lymphoma

    PubMed Central

    Bibas, Michele; Antinori, Andrea

    2009-01-01

    HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART) (1). Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV), a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL), Hodgkin disease (HD), systemic non Hodgkin lymphoma (NHL), primary central nervous system lymphoma (PCNSL), nasopharyngeal carcinoma (NC). Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein. PMID:21416008

  14. Suppressor T cell clones from patients with acute Epstein-Barr virus-induced infectious mononucleosis.

    PubMed Central

    Wang, F; Blaese, R M; Zoon, K C; Tosato, G

    1987-01-01

    Suppression and/or cytotoxicity are believed to play an important role in the defense against Epstein-Barr virus (EBV) infection. To analyze the role of suppressor T cells in relation to EBV, we sought to clone and study these T cells. Analysis of 152 T cell clones derived from the peripheral blood of two patients with acute EBV-induced infectious mononucleosis (IM) yielded 11 highly suppressive clones that had no cytotoxic activity for the natural killer sensitive K562 cell line, an autologous EBV-infected cell line, or an allogeneic EBV-infected B cell line. Four of six suppressor T cell clones also profoundly inhibited EBV-induced immunoglobulin production, and five of five clones delayed the outgrowth of immortalized cells. These results indicate that during acute IM, suppressor T cells capable of inhibiting B cell activation in the absence of cytotoxicity can be identified, and may play a key role in the control of EBV infection. Images PMID:3025263

  15. Acute HIV infection - New York City, 2008.

    PubMed

    2009-11-27

    Acute human immunodeficiency virus (HIV) infection (AHI) is a highly infectious phase of disease that lasts approximately 2 months and is characterized by nonspecific clinical symptoms. AHI contributes disproportionately to HIV transmission because it is associated with a high level of viremia, despite negative or indeterminate antibody (Ab) tests. Diagnosis of AHI with individual or pooled nucleic acid amplification tests (p-NAAT) can enable infected persons to adopt behaviors that reduce HIV transmission, facilitate partner referral for counseling and testing, and identify social networks of persons with elevated rates of HIV transmission. The national HIV surveillance case definition does not distinguish AHI from other stages of HIV infection, and the frequency of AHI among reported HIV cases is unknown. In 2008, to increase detection of AHI and demonstrate the feasibility of AHI surveillance, the New York City Department of Health and Mental Hygiene (NYC DOHMH) initiated p-NAAT screening at four sexually transmitted disease (STD) clinics and enhanced citywide HIV surveillance (using a standard case definition) to differentiate AHI among newly reported cases. Seventy cases of AHI (representing 1.9% of all 3,635 HIV diagnoses reported in New York City) were identified: 53 cases from enhanced surveillance and 17 cases from p-NAAT screening (representing 9% of 198 HIV diagnoses at the four clinics). Men who have sex with men (MSM) constituted 81% of AHI cases. Screening STD clinic patients, especially MSM, with p-NAAT can identify additional cases of HIV infection. Surveillance for AHI is feasible and can identify circumstances in which HIV prevention efforts should be intensified. PMID:19940835

  16. 5-hydroxymethylation of the EBV genome regulates the latent to lytic switch

    PubMed Central

    Wille, Coral K.; Nawandar, Dhananjay M.; Henning, Amanda N.; Ma, Shidong; Oetting, Kayla M.; Lee, Dennis; Lambert, Paul; Johannsen, Eric C.; Kenney, Shannon C.

    2015-01-01

    Latent Epstein–Barr virus (EBV) infection and cellular hypermethylation are hallmarks of undifferentiated nasopharyngeal carcinoma (NPC). However, EBV infection of normal oral epithelial cells is confined to differentiated cells and is lytic. Here we demonstrate that the EBV genome can become 5-hydroxymethylated and that this DNA modification affects EBV lytic reactivation. We show that global 5-hydroxymethylcytosine (5hmC)-modified DNA accumulates during normal epithelial-cell differentiation, whereas EBV+ NPCs have little if any 5hmC-modified DNA. Furthermore, we find that increasing cellular ten–eleven translocation (TET) activity [which converts methylated cytosine (5mC) to 5hmC] decreases methylation, and increases 5hmC modification, of lytic EBV promoters in EBV-infected cell lines containing highly methylated viral genomes. Conversely, inhibition of endogenous TET activity increases lytic EBV promoter methylation in an EBV-infected telomerase-immortalized normal oral keratinocyte (NOKs) cell line where lytic viral promoters are largely unmethylated. We demonstrate that these cytosine modifications differentially affect the ability of the two EBV immediate-early proteins, BZLF1 (Z) and BRLF1 (R), to induce the lytic form of viral infection. Although methylation of lytic EBV promoters increases Z-mediated and inhibits R-mediated lytic reactivation, 5hmC modification of lytic EBV promoters has the opposite effect. We also identify a specific CpG-containing Z-binding site on the BRLF1 promoter that must be methylated for Z-mediated viral reactivation and show that TET-mediated 5hmC modification of this site in NOKs prevents Z-mediated viral reactivation. Decreased 5-hydroxymethylation of cellular and viral genes may contribute to NPC formation. PMID:26663912

  17. 5-hydroxymethylation of the EBV genome regulates the latent to lytic switch.

    PubMed

    Wille, Coral K; Nawandar, Dhananjay M; Henning, Amanda N; Ma, Shidong; Oetting, Kayla M; Lee, Dennis; Lambert, Paul; Johannsen, Eric C; Kenney, Shannon C

    2015-12-29

    Latent Epstein-Barr virus (EBV) infection and cellular hypermethylation are hallmarks of undifferentiated nasopharyngeal carcinoma (NPC). However, EBV infection of normal oral epithelial cells is confined to differentiated cells and is lytic. Here we demonstrate that the EBV genome can become 5-hydroxymethylated and that this DNA modification affects EBV lytic reactivation. We show that global 5-hydroxymethylcytosine (5hmC)-modified DNA accumulates during normal epithelial-cell differentiation, whereas EBV+ NPCs have little if any 5hmC-modified DNA. Furthermore, we find that increasing cellular ten-eleven translocation (TET) activity [which converts methylated cytosine (5mC) to 5hmC] decreases methylation, and increases 5hmC modification, of lytic EBV promoters in EBV-infected cell lines containing highly methylated viral genomes. Conversely, inhibition of endogenous TET activity increases lytic EBV promoter methylation in an EBV-infected telomerase-immortalized normal oral keratinocyte (NOKs) cell line where lytic viral promoters are largely unmethylated. We demonstrate that these cytosine modifications differentially affect the ability of the two EBV immediate-early proteins, BZLF1 (Z) and BRLF1 (R), to induce the lytic form of viral infection. Although methylation of lytic EBV promoters increases Z-mediated and inhibits R-mediated lytic reactivation, 5hmC modification of lytic EBV promoters has the opposite effect. We also identify a specific CpG-containing Z-binding site on the BRLF1 promoter that must be methylated for Z-mediated viral reactivation and show that TET-mediated 5hmC modification of this site in NOKs prevents Z-mediated viral reactivation. Decreased 5-hydroxymethylation of cellular and viral genes may contribute to NPC formation. PMID:26663912

  18. Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies.

    PubMed

    Little, Susan J

    Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T-cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID:27398768

  19. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

    PubMed

    Theochari, Evangelia; Vincent-Smith, Lisa; Ellis, Cathy

    2015-01-01

    Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis. PMID:25739795

  20. Effect of high dose vitamin C on Epstein-Barr viral infection

    PubMed Central

    Mikirova, Nina A.; Hunninghake, Ronald

    2014-01-01

    Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection. Material/Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D. Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro. PMID:24793092

  1. Epstein-Barr virus (EBV) association and latency profile in pediatric Burkitt's lymphoma: experience of a single institution in Argentina.

    PubMed

    Lara, Julia; Cohen, Melina; De Matteo, Elena; Aversa, Luis; Preciado, Maria Victoria; Chabay, Paola

    2014-05-01

    The aim of this study is to characterize EBV expression and latency pattern in pediatric Burkitt's lymphoma in a single institution in Argentina. EBV-encoded RNA or protein was analyzed in 27 patients. EBERs was expressed in 37% of patients (29% of immunocompetent and 100% of immunosuppressed patients). EBV-positive cases were observed exclusively in patients younger than 5 years old. EBV association with immunocompetent patients exhibits the sporadic pattern in region under study, while its presence in patients infected with HIV was higher than described previously. EBV latency I profile was present in most of the patients, except for two immunosuppressed patients who displayed LMP1 expression. PMID:24027016

  2. Meditation or Exercise May Help Acute Respiratory Infections

    MedlinePlus

    ... U V W X Y Z Meditation or Exercise May Help Acute Respiratory Infections, Study Finds Share: © ... of three groups: a mindfulness meditation group, an exercise group, or a wait-list control group. Participants ...

  3. EBV-Infection in Cardiac and Non-Cardiac Gastric Adenocarcinomas is Associated with Promoter Methylation of p16, p14 and APC, but not hMLH1

    PubMed Central

    Geddert, Helene; zur Hausen, Axel; Gabbert, Helmut E.; Sarbia, Mario

    2010-01-01

    Background: Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV. Methods: One hundred GC were tested by RNA-in situ hybridization for the presence of EBV by EBV-encoded small RNA (EBER). Aberrant promoter methylation was investigated by methylation-specific real-time PCR for p16, p14, APC and hMLH1. P16 protein expression was assessed by immunohistochemistry. Results: In our selected study cohort, EBER-transcripts were detected in 19.6% (18/92) of GC. EBV-positive GC revealed significantly more often gene hypermethylation of p16, p14 and APC (p < 0.0001, p < 0.0001 and p = 0.02, respectively) than EBV-negative GC. The majority of GC with p16 hypermethylation showed a p16 protein loss (22/28). In contrast, no correlation between the presence of EBV and hMLH1 hypermethylation was found (p = 0.7). EBV-positive GC showed a trend towards non-cardiac location (p = 0.06) and lower stages (I/II) according to the WHO (p = 0.05). Conclusion: Hypermethylation of tumor suppressor genes is significantly more frequent in EBV-associated GC compared to EBV-negative GC. Our data add new insights to the role of EBV in gastric carcinogenesis and underline that EBV-associated GC comprise a distinct molecular-pathologic as well as a distinct clinicopathological entity of GC. PMID:20978327

  4. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion. PMID:25745498

  5. Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature.

    PubMed

    Ramos-Casals, Manuel; Cuadrado, María José; Alba, Paula; Sanna, Giovanni; Brito-Zerón, Pilar; Bertolaccini, Laura; Babini, Alejandra; Moreno, Asunción; D'Cruz, David; Khamashta, Munther A

    2008-11-01

    Few studies have evaluated the impact of viral infections on the daily management of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and clinical features of acute viral infections arising in patients with SLE and their influence on the diagnosis, prognosis, and treatment of SLE. Cases occurring within the last 5 years were selected from the databases of 3 large teaching hospitals. Acute viral infections were confirmed by the identification of specific antiviral IgM antibodies and subsequent seroconversion with detection of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive of viral infection were confirmed by direct identification of the virus or viruses in tissue samples. We performed a MEDLINE search for additional cases reported between January 1985 and March 2008. We included 88 cases (23 from our clinics and 65 from the literature review) of acute viral infections in patients with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of the 1997 SLE criteria) associated with infection by human parvovirus B19 (n = 15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis A virus (n = 1). The remaining 63 cases of acute viral infections arose in patients already diagnosed with SLE: in 18 patients, symptoms related to infection mimicked a lupus flare, 36 patients, including 1 patient from the former group who presented with both conditions, presented organ-specific viral infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10 patients presented a severe, multiorgan process similar to that described in catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n = 2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients and disclosed disseminated herpetic

  6. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication.

    PubMed

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  7. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

    PubMed Central

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-01

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

  8. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    SciTech Connect

    Klein, George; Klein, Eva; Kashuba, Elena

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  9. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  10. Acute intestinal infections of non-dysenteric etiology*

    PubMed Central

    Linetskaya-Novgorodskaya, E. M.

    1959-01-01

    Recent work on the epidemiology and microbiology of acute intestinal infections has brought about a revision of long-held views as to many of their characteristics and as to their grouping. This paper deals with these infections in the light of this recent work, with particular reference to findings made in Leningrad. PMID:14417237

  11. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. Acute Cytomegalovirus Infection as a Cause of Venous Thromboembolism

    PubMed Central

    Rinaldi, Francesca; Lissandrin, Raffaella; Mojoli, Francesco; Baldanti, Fausto; Brunetti, Enrico; Pascarella, Michela; Giordani, Maria Teresa

    2014-01-01

    Acute Human Cytomegalovirus (HCMV) infection is an unusual cause of venous thromboembolism, a potentially life-threatening condition. Thrombus formation can occur at the onset of the disease or later during the recovery and may also occur in the absence of acute HCMV hepatitis. It is likely due to both vascular endothelium damage caused by HCMV and impairment of the clotting balance caused by the virus itself. Here we report on two immunocompetent women with splanchnic thrombosis that occurred during the course of acute HCMV infection. Although the prevalence of venous thrombosis in patients with acute HCMV infection is unknown, physicians should be aware of its occurrence, particularly in immunocompetent patients presenting with fever and unexplained abdominal pain. PMID:24959338

  13. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  14. Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

    PubMed Central

    Wang, Jianguo; Lyu, Xiaoming; Chen, Yuxiang; Liu, Jinkun; Cai, Hongbing; Wang, Ying; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy. PMID:25691053

  15. Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations.

    PubMed

    Glaser, Sally L; Gulley, Margaret L; Clarke, Christina A; Keegan, Theresa H; Chang, Ellen T; Shema, Sarah J; Craig, Fiona E; Digiuseppe, Joseph A; Dorfman, Ronald F; Mann, Risa B; Anton-Culver, Hoda; Ambinder, Richard F

    2008-10-01

    Epstein-Barr virus (EBV) is detected in the tumor cells of some but not all Hodgkin lymphoma (HL) patients, and evidence indicates that EBV-positive and -negative HL are distinct entities. Racial/ethnic variation in EBV-positive HL in international comparisons suggests etiologic roles for environmental and genetic factors, but these studies used clinical series and evaluated EBV presence by differing protocols. Therefore, we evaluated EBV presence in the tumors of a large (n = 1,032), racially and sociodemographically diverse series of California incident classical HL cases with uniform pathology re-review and EBV detection methods. Tumor EBV-positivity was associated with Hispanic and Asian/Pacific Islander (API) but not black race/ethnicity, irrespective of demographic and clinical factors. Complex race-specific associations were observed between EBV-positive HL and age, sex, histology, stage, neighborhood socioeconomic status (SES), and birth place. In Hispanics, EBV-positive HL was associated not only with young and older age, male sex, and mixed cellularity histology, but also with foreign birth and lower SES in females, suggesting immune function responses to correlates of early childhood experience and later environmental exposures, respectively, as well as of pregnancy. For APIs, a lack of association with birth place may reflect the higher SES of API than Hispanic immigrants. In blacks, EBV-positive HL was associated with later-stage disease, consistent with racial/ethnic variation in certain cytokine polymorphisms. The racial/ethnic variation in our findings suggests that EBV-positive HL results from an intricate interplay of early- and later-life environmental, hormonal, and genetic factors leading to depressed immune function and poorly controlled EBV infection. PMID:18646185

  16. [A Case of Severe Chronic Active Epstein-Barr Virus Infection with Aplastic Anemia and Hepatitis].

    PubMed

    Lee, Ja In; Lee, Sung Won; Han, Nam Ik; Ro, Sang Mi; Noh, Yong-Sun; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2016-01-25

    Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV-related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/μg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis. PMID:26809631

  17. The cytokines effect on EBV-immortalized human B cells producing antisperm antibody.

    PubMed

    Fiszer, D; Niedbała, W; Fernandez, N; Kurpisz, M

    1992-01-01

    We have analyzed the antisperm antibody production of autoimmunized male subjects using Epstein-Barr virus (EBV) immortalization of B lymphocytes. We evaluated the influence of several in vitro culture variants applied prior to EBV infection on the frequence of antibody-producing cells and affinity of secreted antibodies. The following variants were applied: a) polyclonal antigenic stimulation of lymphocytes with PWM, b) PWM (pokeweed mitogen) + IL-2 + interferon gamma and c) PWM + IL-2 + interferon gamma + sperm antigenic extract. The variants where the cytokines were added did not increase the frequency of EBV-infected antibody-producing cells as comparing to EBV infection previously amplified by the use of polyclonal activator. Furthermore the cytokine activation either in combination with mitogen or in vitro secondary antigenic sensitization (prior to EBV transformation) did not seem to have beneficial effect on affinity of antibodies produced by EBV-infected cells in comparison to straight EBV infection. On the other hand, the attempt to promote an immunoglobulin secretion (IgM) by previously obtained human-human antisperm hybridomas by adding of IL-2 was quite successful. PMID:1338684

  18. About Epstein-Barr Virus (EBV)

    MedlinePlus

    ... Providers Laboratory Testing References & Resources About Epstein-Barr Virus (EBV) Recommend on Facebook Tweet Share Compartir On ... Page Symptoms Transmission Diagnosis Prevention & Treatment Epstein-Barr virus (EBV), also known as human herpesvirus 4, is ...

  19. Differential expression of EBV proteins LMP1 and BHFR1 in EBV-associated gastric and nasopharyngeal cancer tissues

    PubMed Central

    WANG, AILIANG; ZHANG, WEI; JIN, MENG; ZHANG, JIANBO; LI, SHENG; TONG, FENG; ZHOU, YANBING

    2016-01-01

    Epstein-Barr virus (EBV) infection is associated with the development of T cell lymphoma, nasopharyngeal cancer (NPC), and EBV-associated gastric cancer (EBVaGC). This study assessed the expression of the EBV-associated proteins latent membrane protein 1 (LMP1) and BamHI-A rightward frame 1 (BARF1) in NPC and EBVaGC tissue specimens and determined their association with clinicopathological data, microvessel density (MVD) and micro-lymphatic vessel density (MLVD). This study collected 600 gastric cancer and 75 NPC tissue samples. EBV infection was assessed using in situ hybridization, and LMP1 and BARF1 expression was assessed using immunohistochemistry. The levels of MVD and MLVD were assessed using immunostaining of vascular endothelial growth factor (VEGF)-C, CD34, and lymphatic vessel endothelial receptor 1 (LYVE-1). Among the 600 gastric cancer cases, 30 were positive for EBV infection, which was shown to be associated with the age of patients (P=0.073), tumor differentiation (P<0.0001), tumor location (P<0.0001) and lymph node metastasis (P<0.0001). In these 30 EBVaGC cases, only one case was weakly positive for LMP1, but 17 cases were BARF1 positive. BARF1 expression was associated with lymph node metastasis of EBVaGC and the level of MLVD. Furthermore, 61 (81%) of 75 NPC patients were EBV positive, among which 38 cases were LMP-1 positive (62.3%) and LMP1 expression was associated with tumor-node-metastasis stage (P=0.011) and lymph node metastasis (P=0.041). MLVD was significantly higher in LMP1-positive cases than LMP1-negative cases. There were only 8 (13.3%) cases positive for BARF1 expression. In conclusion, EBV infection exhibits a role in gastric cancer and NPC development; however, expression of EBV-associated proteins LMP1 and BARF1 have differential functions during tumorigenesis of these two types of cancer. PMID:27052804

  20. Human bocavirus in children with acute respiratory infections in Vietnam.

    PubMed

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. PMID:24123072

  1. Comprehensive profiling of EBV gene expression in nasopharyngeal carcinoma through paired-end transcriptome sequencing.

    PubMed

    Hu, Lijuan; Lin, Zhirui; Wu, Yanheng; Dong, Juqin; Zhao, Bo; Cheng, Yanbing; Huang, Peiyu; Xu, Lihua; Xia, Tianliang; Xiong, Dan; Wang, Hongbo; Li, Manzhi; Guo, Ling; Kieff, Elliott; Zeng, Yixin; Zhong, Qian; Zeng, Musheng

    2016-03-01

    The latent expression pattern of Epstein-Barr Virus (EBV) genes in nasopharyngeal carcinoma (NPC) has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type III latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through realtime PCR.We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type III latency and lytic genes. This study provided further insights into the potential role of EBV in the development of NPC. PMID:26969667

  2. Epstein–Barr virus-associated acute cholecystitis in a teenager

    PubMed Central

    De Alwis, Y; Saleem, M

    2013-01-01

    A 14-year-old girl was admitted to hospital with fever, headache, sore throat and abdominal pain. Her blood lymphocyte count and inflammatory markers were raised. Acute Epstein–Barr virus (EBV) infection was suspected and confirmed serologically and by measuring the viral load. On day 7, she developed jaundice with abnormal liver function tests. An abdominal ultrasound scan revealed thickening of the gallbladder and bile duct walls without calculi suggesting acute acalculous cholecystitis. The patient improved slowly with symptomatic treatment, and a repeat ultrasound scan six months later was normal. Acalculous cholecystitis is a rare complication of EBV infection and usually has a good prognosis.

  3. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection.

    PubMed

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  4. Acute hantavirus infection induces galectin-3-binding protein.

    PubMed

    Hepojoki, Jussi; Strandin, Tomas; Hetzel, Udo; Sironen, Tarja; Klingström, Jonas; Sane, Jussi; Mäkelä, Satu; Mustonen, Jukka; Meri, Seppo; Lundkvist, Ake; Vapalahti, Olli; Lankinen, Hilkka; Vaheri, Antti

    2014-11-01

    Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. PMID:25013204

  5. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed. PMID:27018033

  6. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  7. Human peripheral blood and bone marrow Epstein-Barr virus-specific T-cell repertoire in latent infection reveals distinct memory T-cell subsets.

    PubMed

    Guerreiro, Manuel; Na, Il-Kang; Letsch, Anne; Haase, Doreen; Bauer, Sandra; Meisel, Christian; Roemhild, Andy; Reinke, Petra; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2010-06-01

    EBV infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-gamma-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN-gamma alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy virus carriers are indeed IL-2- and/or TNF-producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV-specific CD4(+) and CD8(+) T cells retained a CC-chemokine receptor 7 (CCR7)-positive memory phenotype. Based on their cytokine profiles, six different EBV-specific T-cell subsets could be distinguished with TNF-single or TNF/IL-2-double producing cells expressing the highest CCR7 levels resembling early-differentiated memory T cells. Our study delineates the memory T-cell profile of a protective immune response and provides a basis for analyzing T-cell responses in EBV-associated diseases. PMID:20232341

  8. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  9. Role of EBNA-3 Family Proteins in EBV Associated B-cell Lymphomagenesis

    PubMed Central

    Bhattacharjee, Shaoni; Ghosh Roy, Shatadru; Bose, Priyanka; Saha, Abhik

    2016-01-01

    Epstein-Barr virus (EBV) is highly ubiquitous in human population and establishes a lifelong asymptomatic infection within the infected host unless the immune system is compromised. Following initial infection in the oropharyngeal epithelial cells, EBV primarily infects naive B-lymphocytes and develops a number of B-cell lymphomas particularly in immune-deficient individuals. In vitro, EBV can also infect and subsequently transform quiescent B-lymphocytes into continuously proliferating lymphoblastoid cell lines (LCLs) resembling EBV-induced lymphoproliferative disorders in which a subset of latent transcripts are detected. Genetic studies revealed that EBNA-3 family comprising of three adjacent genes in the viral genome—EBNA-3A and -3C, but not -3B, are critical for B-cell transformation. Nevertheless, all three proteins appear to significantly contribute to maintain the overall proliferation and viability of transformed cells, suggesting a critical role in lymphoma development. Apart from functioning as important viral transcriptional regulators, EBNA-3 proteins associate with many cellular proteins in different signaling networks, providing a suitable platform for lifelong survival of the virus and concurrent lymphoma development in the infected host. The chapter describes the function of each these EBV nuclear antigen 3 proteins employed by the virus as a means to understand viral pathogenesis of several EBV-associated B-cell malignancies. PMID:27092119

  10. CTCF prevents the epigenetic drift of EBV latency promoter Qp.

    PubMed

    Tempera, Italo; Wiedmer, Andreas; Dheekollu, Jayaraju; Lieberman, Paul M

    2010-01-01

    The establishment and maintenance of Epstein-Barr Virus (EBV) latent infection requires distinct viral gene expression programs. These gene expression programs, termed latency types, are determined largely by promoter selection, and controlled through the interplay between cell-type specific transcription factors, chromatin structure, and epigenetic modifications. We used a genome-wide chromatin-immunoprecipitation (ChIP) assay to identify epigenetic modifications that correlate with different latency types. We found that the chromatin insulator protein CTCF binds at several key regulatory nodes in the EBV genome and may compartmentalize epigenetic modifications across the viral genome. Highly enriched CTCF binding sites were identified at the promoter regions upstream of Cp, Wp, EBERs, and Qp. Since Qp is essential for long-term maintenance of viral genomes in type I latency and epithelial cell infections, we focused on the role of CTCF in regulating Qp. Purified CTCF bound approximately 40 bp upstream of the EBNA1 binding sites located at +10 bp relative to the transcriptional initiation site at Qp. Mutagenesis of the CTCF binding site in EBV bacmids resulted in a decrease in the recovery of stable hygromycin-resistant episomes in 293 cells. EBV lacking the Qp CTCF site showed a decrease in Qp transcription initiation and a corresponding increase in Cp and Fp promoter utilization at 8 weeks post-transfection. However, by 16 weeks post-transfection, bacmids lacking CTCF sites had no detectable Qp transcription and showed high levels of histone H3 K9 methylation and CpG DNA methylation at the Qp initiation site. These findings provide direct genetic evidence that CTCF functions as a chromatin insulator that prevents the promiscuous transcription of surrounding genes and blocks the epigenetic silencing of an essential promoter, Qp, during EBV latent infection. PMID:20730088

  11. Increased Frequency of EBV-Specific Effector Memory CD8+ T Cells Correlates with Higher Viral Load in Rheumatoid Arthritis1

    PubMed Central

    Lünemann, Jan D.; Frey, Oliver; Eidner, Thorsten; Baier, Michael; Roberts, Susanne; Sashihara, Junji; Volkmer, Rudolf; Cohen, Jeffrey I.; Hein, Gert; Kamradt, Thomas; Münz, Christian

    2008-01-01

    EBV is a candidate trigger of rheumatoid arthritis (RA). We determined both EBV-specific T cell and B cell responses and cell-associated EBV DNA copies in patients with RA and demographically matched healthy virus carriers. Patients with RA showed increased and broadened IgG responses to lytic and latent EBV-encoded Ags and 7-fold higher levels of EBV copy numbers in circulating blood cells. Additionally, patients with RA exhibited substantial expansions of CD8+ T cells specific for pooled EBV Ags expressed during both B cell transformation and productive viral replication and the frequency of CD8+ T cells specific for these Ags correlated with cellular EBV copy numbers. In contrast, CD4+ T cell responses to EBV and T cell responses to human CMV Ags were unchanged, altogether arguing against a defective control of latent EBV infection in RA. Our data show that the regulation of EBV infection is perturbed in RA and suggest that increased EBV-specific effector T cell and Ab responses are driven by an elevated EBV load in RA. PMID:18606650

  12. Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

    PubMed Central

    Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

    2013-01-01

    Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

  13. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

    PubMed Central

    Burns, David M.; Tierney, Rose; Shannon-Lowe, Claire; Croudace, Jo; Inman, Charlotte; Abbotts, Ben; Nagra, Sandeep; Fox, Christopher P.; Chaganti, Sridhar; Craddock, Charles F.; Moss, Paul; Rickinson, Alan B.; Rowe, Martin

    2015-01-01

    Allogeneic stem cell transplantation (allo-HSCT) provides a unique opportunity to track Epstein-Barr virus (EBV) infection in the context of the reconstituting B-cell system. Although many allo-HSCT recipients maintain low or undetectable levels of EBV DNA posttransplant, a significant proportion exhibit elevated and rapidly increasing EBV loads which, if left untreated, may lead to potentially fatal EBV-associated posttransplant lymphoproliferative disease. Intriguingly, this high-level EBV reactivation typically arises in the first 3 months posttransplant, at a time when the peripheral blood contains low numbers of CD27+ memory cells which are the site of EBV persistence in healthy immunocompetent donors. To investigate this apparent paradox, we prospectively monitored EBV levels and B-cell reconstitution in a cohort of allo-HSCT patients for up to 12 months posttransplant. In patients with low or undetectable levels of EBV, the circulating B-cell pool consisted predominantly of transitional and naive cells, with a marked deficiency of CD27+ memory cells which lasted >12 months. However, among patients with high EBV loads, there was a significant increase in both the proportion and number of CD27+ memory B cells. Analysis of sorted CD27+ memory B cells from these patients revealed that this population was preferentially infected with EBV, expressed EBV latent transcripts associated with B-cell growth transformation, had a plasmablastic phenotype, and frequently expressed the proliferation marker Ki-67. These findings suggest that high-level EBV reactivation following allo-HSCT may drive the expansion of latently infected CD27+ B lymphoblasts in the peripheral blood. PMID:26450987

  14. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event.

    PubMed

    Burns, David M; Tierney, Rose; Shannon-Lowe, Claire; Croudace, Jo; Inman, Charlotte; Abbotts, Ben; Nagra, Sandeep; Fox, Christopher P; Chaganti, Sridhar; Craddock, Charles F; Moss, Paul; Rickinson, Alan B; Rowe, Martin; Bell, Andrew I

    2015-12-17

    Allogeneic stem cell transplantation (allo-HSCT) provides a unique opportunity to track Epstein-Barr virus (EBV) infection in the context of the reconstituting B-cell system. Although many allo-HSCT recipients maintain low or undetectable levels of EBV DNA posttransplant, a significant proportion exhibit elevated and rapidly increasing EBV loads which, if left untreated, may lead to potentially fatal EBV-associated posttransplant lymphoproliferative disease. Intriguingly, this high-level EBV reactivation typically arises in the first 3 months posttransplant, at a time when the peripheral blood contains low numbers of CD27+ memory cells which are the site of EBV persistence in healthy immunocompetent donors. To investigate this apparent paradox, we prospectively monitored EBV levels and B-cell reconstitution in a cohort of allo-HSCT patients for up to 12 months posttransplant. In patients with low or undetectable levels of EBV, the circulating B-cell pool consisted predominantly of transitional and naive cells, with a marked deficiency of CD27+ memory cells which lasted >12 months. However, among patients with high EBV loads, there was a significant increase in both the proportion and number of CD27+ memory B cells. Analysis of sorted CD27+ memory B cells from these patients revealed that this population was preferentially infected with EBV, expressed EBV latent transcripts associated with B-cell growth transformation, had a plasmablastic phenotype, and frequently expressed the proliferation marker Ki-67. These findings suggest that high-level EBV reactivation following allo-HSCT may drive the expansion of latently infected CD27+ B lymphoblasts in the peripheral blood. PMID:26450987

  15. Repeated detection of gas in the portal vein after liver transplantation: A sign of EBV-associated post-transplant lymphoproliferation?

    PubMed

    Wallot, Michael A; Klepper, Jörg; Clapuyt, Philippe; Dirsch, Olaf; Malagó, Max; Reding, Raymond; Otte, Jean Bernard; Sokal, Etienne M

    2002-08-01

    A 1-yr-old child presented with intractable right sided pleural effusion and progressive clinical deterioration 3 weeks after liver transplantation for Alagille Syndrome. He had been treated successfully for severe acute rejection before. Ultrasound and Doppler mode studies repeatedly demonstrated air in the portal vein. Intra-abdominal and intra-thoracic lymphoproliferation was detected, and EBV virus load and serology were suggestive of primary EBV infection. Liver biopsy revealed blast-like infiltrates of B-cells, considered diagnostic for post-transplant lymphoproliferative disease. The disease resolved upon reduction of immunosuppression. We suggest that the detection of portal vein gas in pediatric liver transplant recipients beyond the early post-operative period may be a sign of intra-abdominal post-transplant lymphoproliferative disease. PMID:12234275

  16. Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.

    PubMed

    Vashishtha, Vipin M; Thacker, Sandeep; Namjoshi, Gajanan Sudhir

    2016-07-01

    Documentation of rotavirus diarrhea in a rural, resource-poor setting is a difficult task. We analyzed stool samples of 103 children admitted for acute diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside immunochromatography kit. Rotavirus infection was detected in 47 out of total of 103 children (45.6%). PMID:27508549

  17. Acute Borrelia infection inducing an APMPPE-like picture.

    PubMed

    Al Mousa, Munjid; Koch, Frank

    2016-12-01

    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection. PMID:27294731

  18. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  19. Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers.

    PubMed

    Elgui de Oliveira, Deilson; Müller-Coan, Bárbara G; Pagano, Joseph S

    2016-08-01

    Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein-Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial-mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers. PMID:27068530

  20. Studies of EBV-lymphoid cell interactions in two patients with the X-linked lymphoproliferative syndrome: normal EBV-specific HLA-restricted cytotoxicity.

    PubMed

    Rousset, F; Souillet, G; Roncarolo, M G; Lamelin, J P

    1986-02-01

    Two X-linked lymphoproliferative syndrome (XLP) patients with the hypogammaglobulinemia phenotype were investigated at a time remote from their primary infection with the Epstein-Barr virus (EBV). The lymphoblastoid cell lines derived from these patients expressed the phenotypic markers characteristic of normal mature B lymphocytes and produced normal levels of immunoglobulins (Ig). These observations imply that at least some of their B cells are phenotypically normal. The natural killer (NK) activity of the two patients was low. In one patient, activated lymphocyte killer (ALK) activity was inefficient. These two XLP patients expressed a normal EBV-specific, HLA-restricted cytotoxic activity. It thus appears, from the present findings and those in cases published previously (6/11 patients expressing normal EBV-specific cytotoxic activity), that the notion of poor specific T cell memory for EBV may not be as pivotal ass suggested or, alternatively, that this defect may not be common in hypogammaglobulinemic survivors. PMID:3009061

  1. [Anaerobic-aerobic infection in acute appendicitis].

    PubMed

    Mamchich, V I; Ulitovskiĭ, I V; Savich, E I; Znamenskiĭ, V A; Beliaeva, O A

    1998-01-01

    362 patients with acute appendicitis (AA) were examined. For microbiological diagnosis of aerobic and anaerobic nonclostridial microflora we used complex accelerated methods (including evaluation of gram-negative microorganisms in comparison with tinctorial-fermentative method of differential staining according to oxygen sensitivity of catalasopositive together with aerobic and cathalasonegative anaerobic microorganisms) as well as complete bacteriologic examination with determination of sensitivity of the above microorganism to antimicrobial remedies. High rate of aerobic-anaerobic microbial associations and substantial identity of microflora from appendicis and exudate from abdominal cavity was revealed, which evidenced the leading role of endogenous microorganisms in etiology and pathogenesis of AA and peritonitis i. e. autoinfection. In patients with destructive forms of AA, complicated by peritonitis it is recommended to use the accelerated method of examination of pathologic material as well as the complete scheme of examination with the identification of the isolated microorganisms and the correction of antibiotic treatment. PMID:9511291

  2. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  3. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment

    PubMed Central

    Gru, A. A.; Haverkos, B. H.; Freud, A. G.; Hastings, J.; Nowacki, N. B.; Barrionuevo, C.; Vigil, C. E.; Rochford, R.; Natkunam, Y.; Baiocchi, R. A.

    2015-01-01

    While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes. PMID:26449716

  4. Current Perspectives of Prophylaxis and Management of Acute Infective Endophthalmitis.

    PubMed

    Tranos, Paris; Dervenis, Nikolaos; Vakalis, Athanasios N; Asteriadis, Solon; Stavrakas, Panagiotis; Konstas, Anastasios G P

    2016-05-01

    Endophthalmitis is an intraocular inflammatory condition which may or may not be caused by infective agents. Noninfectious (sterile) endophthalmitis may be attributable to various causes including postoperative retained soft lens matter or toxicity following introduction of other agents into the eye. Infectious endophthalmitis is further subdivided into endogenous and exogenous. In endogenous endophthalmitis there is hematogenous spread of organisms from a distant source of infection whereas in exogenous endophthalmitis direct microbial inoculation may occur usually following ocular surgery or penetrating eye injury with or without intraocular foreign bodies. Acute infective endophthalmitis is usually exogenous induced by inoculation of pathogens following ocular surgery, open-globe injury and intravitreal injections. More infrequently the infective source is internal and septicemia spreads to the eye resulting in endogenous endophthalmitis. Several risk factors have been implicated including immunosuppression, ocular surface abnormalities, poor surgical wound construction, complicated cataract surgery with vitreous loss and certain types of intraocular lens. Comprehensive guidelines and recommendations on prophylaxis and monitoring of surgical cases have been proposed to minimize the risk of acute endophthalmitis. Early diagnosis and prompt management of infective endophthalmitis employing appropriately selected intravitreal antibiotics are essential to optimize visual outcome. PMID:26935830

  5. ANA testing in the presence of acute and chronic infections.

    PubMed

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings. PMID:27050929

  6. Expression of HSV-1 Receptors in EBV-Associated Lymphoproliferative Disease Determines Susceptibility to Oncolytic HSV

    PubMed Central

    Wang, Pin-Yi; Currier, Mark A; Hansford, Loen; Kaplan, David; Chiocca, E. Antonio; Uchida, Hiroaki; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C.; van Kuppevelt, Toin H.; Mo, Xiaokui; Cripe, Timothy P

    2012-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. Because PKR is a major cellular defense against Herpes simplex virus, and oncolytic HSV-1 (oHSV) mutants have shown promising anti-tumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was most susceptible, NB122R was intermediate, and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas down-regulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a neuroblastoma cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases due to low virus receptor expression but also due to intact anti-viral PKR signaling. PMID:23254370

  7. Whole blood EBV-DNA predicts outcome in diffuse large B-cell lymphoma.

    PubMed

    Tisi, Maria Chiara; Cupelli, Elisa; Santangelo, Rosaria; Maiolo, Elena; Alma, Eleonora; Giachelia, Manuela; Martini, Maurizio; Bellesi, Silvia; D'Alò, Francesco; Voso, Maria Teresa; Pompili, Maurizio; Leone, Giuseppe; Larocca, Luigi Maria; Hohaus, Stefan

    2016-03-01

    An association between Epstein-Barr Virus (EBV) infection and lymphoproliferative diseases has been reported with EBV + diffuse large B cell-lymphoma (DLBCL) of the elderly described as a distinct entity. In a cohort of 218 human immunodeficiency virus (HIV)-negative patients with diffuse large B-cell lymphomas, we detected EBV-DNA in 25% of whole blood (WB) samples at diagnosis. Presence and viral load in WB, mononuclear cells or plasma did not predict the presence of EBV in the tumor biopsy. Positive Hepatitis C virus (HCV) serology was associated with a higher frequency of EBV in WB. Patients with EBV-DNA in WB had a significantly shorter progression-free (p = 0.02) and overall survival (p = 0.05) after immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone). We conclude that detection of EBV in WB is not a surrogate marker for EBV-association in diffuse large B-cell lymphoma, however it associates with worse outcome. PMID:26458141

  8. Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. PMID:26790932

  9. Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection

    PubMed Central

    Rai, Birendra; Ali, Muhammad; Kumar, Varun; Krebit, Ibraheem

    2014-01-01

    We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients. PMID:24928932

  10. Pteropine orthoreovirus infection among out-patients with acute upper respiratory tract infection in Malaysia.

    PubMed

    Voon, Kenny; Tan, Yeh Fong; Leong, Pooi Pooi; Teng, Cheong Lieng; Gunnasekaran, Rajasekaran; Ujang, Kamsiah; Chua, Kaw Bing; Wang, Lin-Fa

    2015-12-01

    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes. PMID:26106066

  11. Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia.

    PubMed

    Liang, Jin-Hua; Gao, Rui; Xia, Yi; Gale, Robert Peter; Chen, Rui-Ze; Yang, Yu-Qiong; Wang, Li; Qu, Xiao-Yan; Qiu, Hai-Rong; Cao, Lei; Hong, Min; Wang, Rong; Wang, Yan; Fan, Lei; Chen, Yao-Yu; Hu, Zhi-Bin; Li, Jian-Yong; Xu, Wei

    2016-01-12

    Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems. PMID:26539641

  12. Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia

    PubMed Central

    Xia, Yi; Gale, Robert Peter; Chen, Rui-Ze; Yang, Yu-Qiong; Wang, Li; Qu, Xiao-Yan; Qiu, Hai-Rong; Cao, Lei; Hong, Min; Wang, Rong; Wang, Yan; Fan, Lei; Chen, Yao-Yu; Hu, Zhi-Bin; Li, Jian-Yong; Xu, Wei

    2016-01-01

    Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems. PMID:26539641

  13. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE. PMID:25883930

  14. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  15. Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV) Lytic Cycle in EBV-Positive Epithelial Malignancies

    PubMed Central

    Choi, Chung King; Ho, Dona N.; Hui, Kwai Fung; Kao, Richard Y.; Chiang, Alan K. S.

    2015-01-01

    Phorbol esters, which are protein kinase C (PKC) activators, and histone deacetylase (HDAC) inhibitors, which cause enhanced acetylation of cellular proteins, are the main classes of chemical inducers of Epstein-Barr virus (EBV) lytic cycle in latently EBV-infected cells acting through the PKC pathway. Chemical inducers which induce EBV lytic cycle through alternative cellular pathways may aid in defining the mechanisms leading to lytic cycle reactivation and improve cells’ responsiveness towards lytic induction. We performed a phenotypic screening on a chemical library of 50,240 novel small organic compounds to identify novel class(es) of strong inducer(s) of EBV lytic cycle in gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC) cells. Five hit compounds were selected after three successive rounds of increasingly stringent screening. All five compounds are structurally diverse from each other and distinct from phorbol esters or HDAC inhibitors. They neither cause hyperacetylation of histone proteins nor significant PKC activation at their working concentrations, suggesting that their biological mode of action are distinct from that of the known chemical inducers. Two of the five compounds with rapid lytic-inducing action were further studied for their mechanisms of induction of EBV lytic cycle. Unlike HDAC inhibitors, lytic induction by both compounds was not inhibited by rottlerin, a specific inhibitor of PKCδ. Interestingly, both compounds could cooperate with HDAC inhibitors to enhance EBV lytic cycle induction in EBV-positive epithelial cancer cells, paving way for the development of strategies to increase cells’ responsiveness towards lytic reactivation. One of the two compounds bears structural resemblance to iron chelators and the other strongly activates the MAPK pathways. These structurally diverse novel organic compounds may represent potential new classes of chemicals that can be used to investigate any alternative mechanism(s) leading to EBV

  16. The requirements of protein & amino acid during acute & chronic infections.

    PubMed

    Kurpad, Anura V

    2006-08-01

    Nutrition and infection interact with each other in a synergistic vicious cycle, leading to an adverse nutritional status and increased susceptibility to infection. Infectious episodes result in hypermetabolism and a negative nitrogen balance which is modulated by hormones, cytokines and other pro-inflammatory mediators, and is compounded by a reduced food intake. The extent of the negative nitrogen balance varies with the type of infection and its duration; however, it is reasonable to suggest that the loss of body protein could be minimized by the provision of dietary nitrogen, although anorexia will limit this. Further, distinctions need to be made about the provision of nutrients or protein during the catabolic and anabolic or recovery phase of the infection, since the capacity of the body to retain protein is enhanced in the anabolic recovery phase. Meeting the increased requirement for protein (and other nutrients) in infection does not imply a complete therapeutic strategy. Infections need to be treated appropriately, with nutrition as an adjunct to the treatment. Prior undernutrition could also impair the body's response to infection, although the weight of the evidence would suggest that this happens more particularly in oedematous undernutrition. In general, the amount of extra protein that would appear to be needed is of the order of 20-25 per cent of the recommended intake, for most infections. In acute infections, this is particularly relevant during the convalescence period. Community trials have suggested that lysine supplementation to the level required for normal daily nutriture, in predominantly wheat eating or potentially lysine deficient communities, improves immune function among other functional nutritional parameters; however, there is as yet insufficient evidence to suggest a specific requirement for amino acids in infections over and above the normal daily requirement as based on recent evidence. Some clinical studies that have showed

  17. Latent Expression of the Epstein-Barr Virus (EBV)-Encoded Major Histocompatibility Complex Class I TAP Inhibitor, BNLF2a, in EBV-Positive Gastric Carcinomas

    PubMed Central

    Strong, Michael J.; Laskow, Thomas; Nakhoul, Hani; Blanchard, Eugene; Liu, Yaozhong; Wang, Xia; Baddoo, Melody; Lin, Zhen; Yin, Qinyan

    2015-01-01

    The Epstein-Barr virus (EBV) BNLF2a gene product provides immune evasion properties to infected cells through inhibition of transporter associated with antigen processing (TAP)-mediated transport of antigen peptides. Although BNLF2a is considered to be a lytic gene, we demonstrate that it is expressed in nearly half of the EBV-associated gastric carcinomas analyzed. Further, we show that BNLF2a expression is dissociated from lytic gene expression. BNLF2a is therefore expressed in this latency setting, potentially helping protect the infected tumor cells from immunosurveillance. PMID:26178981

  18. Pivmecillinam for the treatment of acute uncomplicated urinary infection.

    PubMed

    Nicolle, L E

    1999-12-01

    Pivmecillinam is a beta-lactam antimicrobial marketed almost two decades ago. It has been used widely for the treatment of acute cystitis in selected areas of the world, particularly in Scandinavia. With increasing resistance of community Escherichia coli isolates to trimethoprim and trimethoprim/sulphamethoxazole, as previously observed for ampicillin and sulphonamides, reassessment of empiric antimicrobial regimens for acute uncomplicated urinary infection is necessary. Thus, it is timely to revisit the role of pivmecillinam for the treatment of acute cystitis. Clinical studies document the efficacy of this antimicrobial with short course therapy for acute cystitis, and clinical practice in countries where it has been used for many years confirms its efficacy and tolerability. If this agent were more widely used for empiric treatment for acute cystitis, use of antimicrobials such as the quinolones might be avoided. Further trials to define the comparative efficacy of pivmecillinam with other antimicrobials, and further studies of community resistance in E. coli isolates to this agent are needed. PMID:10692756

  19. Bone and Joint Infections in Children: Acute Hematogenous Osteomyelitis.

    PubMed

    Agarwal, Anil; Aggarwal, Aditya N

    2016-08-01

    Acute hematogenous osteomyelitis (AHO) is one of the commonest bone infection in childhood. Staphylococcus aureus is the commonest organism causing AHO. With use of advanced diagnostic methods, fastidious Kingella kingae is increasingly becoming an important organism in etiology of osteoarticular infections in children under the age of 3 y. The diagnosis of AHO is primarily clinical. The main clinical symptom and sign in AHO is pain and tenderness over the affected bone especially in the metaphyseal region. However, in a neonate the clinical presentation may be subtle and misleading. Laboratory and radiological investigations supplement the clinical findings. The acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently elevated. Ultrasonography and MRI are key imaging modalities for early detection of AHO. Determination of infecting organism in AHO is the key to the correct antibiotic choice, treatment duration and overall management and therefore, organism isolation using blood cultures and site aspiration should be attempted. Several effective antibiotics regimes are available for managing AHO in children. The choice of antibiotic and its duration and mode of delivery requires individualization depending upon severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and child's presentation and the clinical and laboratory response to the treatment. If pus has been evidenced in the soft tissues or bone region, surgical decompression of abscess is mandatory. PMID:26096866

  20. Host-microbiome interactions in acute and chronic respiratory infections.

    PubMed

    Taylor, Steven L; Wesselingh, Steve; Rogers, Geraint B

    2016-05-01

    Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host-microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross-talk between the gastrointestinal and respiratory compartments to microbe-mucosa interactions. PMID:26972325

  1. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  2. Interpreting the Epstein-Barr Virus (EBV) epigenome using high-throughput data.

    PubMed

    Arvey, Aaron; Tempera, Italo; Lieberman, Paul M

    2013-04-01

    The Epstein-Barr virus (EBV) double-stranded DNA genome is subject to extensive epigenetic regulation. Large consortiums and individual labs have generated a vast number of genome-wide data sets on human lymphoblastoid and other cell lines latently infected with EBV. Analysis of these data sets reveals important new information on the properties of the host and viral chromosome structure organization and epigenetic modifications. We discuss the mapping of these data sets and the subsequent insights into the chromatin structure and transcription factor binding patterns on latent EBV genomes. Colocalization of multiple histone modifications and transcription factors at regulatory loci are considered in the context of the biology and regulation of EBV. PMID:23549386

  3. A novel mouse xenotransplantation model of EBV-T/NK-LPD and the application of the mouse model.

    PubMed

    Imadome, Ken-Ichi

    2013-01-01

    Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by proliferation of EBV-infected T or NK cells, is a disease of unknown pathogenesis and requires hematopoietic stem cell transplantation for curative treatment. Here we show that intravenous injection of peripheral blood mononuclear cells (PBMCs) isolated from patients with CAEBV to NOD/Shi-scid/IL-2R γ(null) (NOG) mice leads to engraftment of EBV-infected T or NK cells. Analysis of TCR repertoire identified an identical predominant EBV-infected T-cell clone both in a patient and a mouse transplanted with his PBMCs. EBV-infected T or NK cells infiltrated to most major organs including the liver, spleen, lungs, kidneys, adrenal glands, and intestine, showing histological characteristics of CAEBV. Expression of EBNA1, LMP1, and LMP2A, but not EBNA2, in these cells indicated the latency II program of EBV gene characteristic to CAEBV. High levels of TNF-α, IFN-γ, and RANTES were detected in the peripheral blood of these mice. EBV-containing fractions of either CD8(+), γδT, or NK cell lineages failed to engraft, once they were isolated from PBMCs ; they could engraft only when CD4(+) cell fraction was transplanted in parallel. Isolated EBV-containing CD4(+) T cells, in contrast, did engraft on their own. This is the first report of an animal model of CAEBV and suggest that EBV-infected T or NK cells in CAEBV are not truly neoplastic but are dependent on CD4(+) T cells for their proliferation in vivo. PMID:24390103

  4. Comparing the Bacterial Diversity of Acute and Chronic Dental Root Canal Infections

    PubMed Central

    Santos, Adriana L.; Siqueira, José F.; Rôças, Isabela N.; Jesus, Ederson C.; Rosado, Alexandre S.; Tiedje, James M.

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  5. Comparing the bacterial diversity of acute and chronic dental root canal infections.

    PubMed

    Santos, Adriana L; Siqueira, José F; Rôças, Isabela N; Jesus, Ederson C; Rosado, Alexandre S; Tiedje, James M

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  6. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  7. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection.

    PubMed

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  8. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

    PubMed Central

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M.; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  9. Actinomyces infection causing acute right iliac fossa pain

    PubMed Central

    Govindarajah, Narendranath; Hameed, Waseem; Middleton, Simon; Booth, Michael

    2014-01-01

    This is a case of a 75-year-old man being admitted to the on-call surgical department with acute abdominal pain. On arrival he was clinically dehydrated and shocked with localised pain over McBurney's point and examination findings were suggestive of appendiceal or other colonic pathology. Full blood testing revealed a white cell count of 38×109/L and a C reactive protein (CRP) of 278 mg/L. A CT scan revealed a gallbladder empyema that extended into the right iliac fossa. This case highlights the potential for a hyperdistended gallbladder empyema to present as acute right iliac fossa pain with blood tests suggestive of complicated disease. Further analysis confirmed Actinomyces infection as the underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case serves to remind clinicians of this as a rare potential cause of atypical gallbladder pathology. PMID:24872493

  10. Ataxia and Encephalitis in a Young Adult with EBV Mononucleosis: A Case Report.

    PubMed

    Hussain, Rashid S; Hussain, Naaz A

    2013-01-01

    Neurological manifestations of mononucleosis are extremely rare, occurring in about 1% of all cases. However, when they occur, appropriate treatment must be undertaken to ensure appropriate symptomatic management and reduce morbidity. We present the case of a 25-year-old graduate student with weeklong complaints of fever, sore throat, fatigue, nausea, and "dizziness." She later developed increased sleep requirements, ataxia, vertigo, and nystagmus with a positive EBV IgM titer confirming acute infectious mononucleosis. The patient was clinically diagnosed with EBV-associated cerebellitis and encephalitis, displaying neurological and psychiatric impairment commonly seen in postconcussion syndrome. MRI showed no acute changes. She was started on valacyclovir and a prednisone taper, recovering by the end of twelve weeks. Though corticosteroids and acyclovir are not recommended therapy in patients presenting with EBV-associated ataxia, clinicians may want to keep a low threshold to start these medications in case more serious neurological sequelae develop. PMID:23781357

  11. Microbial transformation from normal oral microbiota to acute endodontic infections

    PubMed Central

    2012-01-01

    Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections). Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals. PMID:22839737

  12. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  13. Acute prevertebral abscess secondary to infected pancreatic pseudocyst

    PubMed Central

    Bhandarkar, Ajay M; Pillai, Suresh; Venkitachalam, Shruti; Anand, Aishwarya

    2014-01-01

    We report a case of a middle aged, man with diabetes who presented with dysphagia and odynophagia. On evaluation, he was diagnosed to have an acute prevertebral abscess with an unusual aetiology, an infected pseudocyst of pancreas. Contrast-enhanced CT revealed an enhancing collection in the prevertebral space extending to the retrogastric space and communicating with the body of the pancreas via the oesophageal hiatus. Transoral incision and drainage of the prevertebral abscess were performed. Nasogastric tube was placed in the prevertebral space for continuous drainage and daily irrigation. Supportive intravenous broad spectrum antibiotic therapy along with the surgical intervention led to the resolution of the prevertebral abscess and the infected pancreatic pseudocyst. PMID:24408943

  14. Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy

    PubMed Central

    Prakash, Gaurav; Thulkar, Sanjay; Arava, Sudheer Kumar; Bakhshi, Sameer

    2012-01-01

    Angioinvasive pulmonary infection from filamentous fungi is not an uncommon occurrence in immunocompromised patients like acute lymphoblastic leukemia (ALL). Rarely, these lesions can spread via the hematogenous route and involve multiple visceral organs. We report a case of a 14-year-old boy with ALL who developed angioinvasive pulmonary aspergillosis early in the course of induction therapy, which was followed by hematogenous dissemination and formation of multiple brain abscesses. The patient was treated with intravenous amphotericin B. There was no response to the therapy and the patient succumbed to disseminated infection. Postmortem lung biopsy confirmed angioinvasive pulmonary aspergillosis. Poor penetration of amphotericin B across the blood-brain barrier could be one of the contributory factors for poor response to antifungal therapy. We discuss the various antifungal agents with respect to their penetration in brain. PMID:23580827

  15. Frequency of Epstein - Barr Virus in Patients Presenting with Acute Febrile Illness in Kenya

    PubMed Central

    Masakhwe, Clement; Ochanda, Horace; Nyakoe, Nancy; Ochiel, Daniel; Waitumbi, John

    2016-01-01

    Background Most acute febrile illnesses (AFI) are usually not associated with a specific diagnosis because of limitations of available diagnostics. This study reports on the frequency of EBV viremia and viral load in children and adults presenting with febrile illness in hospitals in Kenya. Methodology/Principal Findings A pathogen surveillance study was conducted on patients presenting with AFI (N = 796) at outpatient departments in 8 hospitals located in diverse regions of Kenya. Enrollment criterion to the study was fever without a readily diagnosable infection. All the patients had AFI not attributable to the common causes of fever in Kenyan hospitals, such as malaria or rickettsiae, leptospira, brucella and salmonella and they were hence categorized as having AFI of unknown etiology. EBV was detected in blood using quantitative TaqMan-based qPCR targeting a highly conserved BALF5 gene. The overall frequency of EBV viremia in this population was 29.2%, with significantly higher proportion in younger children of <5years (33.8%, p = 0.039) compared to patients aged ≥5 years (26.3% for 5–15 years or 18.8% for >15 years). With respect to geographical localities, the frequency of EBV viremia was higher in the Lake Victoria region (36.4%), compared to Kisii highland (24.6%), Coastal region (22.2%) and Semi-Arid region (25%). Furthermore, patients from the malaria endemic coastal region and the Lake Victoria region presented with significantly higher viremia than individuals from other regions of Kenya. Conclusions/Significance This study provides profiles of EBV in patients with AFI from diverse eco-regions of Kenya. Of significant interest is the high frequency of EBV viremia in younger children. The observed high frequencies of EBV viremia and elevated viral loads in residents of high malaria transmission areas are probably related to malaria induced immune activation and resultant expansion of EBV infected B-cells. PMID:27163791

  16. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    SciTech Connect

    Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  17. EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1

    SciTech Connect

    Chen, Ya-Lin; Tsai, Hsing-Lyn; Peng, Chih-Wen

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Two cell-based reporter platforms were established for screening of EBNA1 inhibitors. Black-Right-Pointing-Pointer EGCG acts as an inhibitor to block EBNA1 binding with the cognate oriP sequence. Black-Right-Pointing-Pointer EGCG debilitates EBNA1-dependent transcription enhancement and episome maintenance. Black-Right-Pointing-Pointer EGCG impairs persistence of EBV latency. Black-Right-Pointing-Pointer EGCG is a potent anti-EBV agent for targeting the latent cascade of EBV. -- Abstract: Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Luc mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 {mu}M EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.

  18. [Circulating immune complexes in acute and prolonged hepatitis A infection].

    PubMed

    Dautović-Krkić, Sajma; Gribajcević, Mehmed

    2002-01-01

    Level and dynamics activity of circulating immune complexes (CiC) and persistence CiC in the sera in the acute and prolonged HAV-infection was examined. In the same time we explored the relation of level and dynamics CiC compared with level, dynamics and persistence length ALT and IgM anti-HAV in sera, longitude excretion HAV Ag in stool and intensity patohistological damage in liver. Research have been undertaken in the prospected study on two groups with 90 patients in total: 60 patients with prolonged form of the hepatitis A, and 30 patients with HAV-infection with normal development. CiC was prescribe with fotometer in sediment of poliethilenglicol, and IgM anti HAV with ELISA technique. Ag-HAV in stool was prescribe with methodImmuno/electro/osmophoresis. Results of examination showed that high level values of CiC had present in all patients with HAV-infection, bat yet middle values of CiC had significantly higher in prolonged forms (p < 0.01). In a case of patients with PTHA CiC persistence almost three times longer than in HAV infection with normal development. The highest value of CiC have been found from one to two weeks after e peak ALT in HAV and in PTHA 4-6 weeks later. Persistence of elevated values CiC responded to the middle length persistence of Igm anti HAV-in the sera. PMID:12378858

  19. Finding those at risk: Acute HIV infection in Newark, NJ

    PubMed Central

    Martin, Eugene G.; Salaru, Gratian; Mohammed, Debbie; Coombs, Robert W.; Paul, Sindy M.; Cadoff, Evan M.

    2014-01-01

    Background A screening strategy combining rapid HIV-1/2 (HIV) antibody testing with pooled HIV-1 RNA testing increases identification of HIV infections, but may have other limitations that restrict its usefulness to all but the highest incidence populations. Objective By combining rapid antibody detection and pooled nucleic acid amplification testing (NAAT) testing, we sought to improve detection of early HIV-1 infections in an urban Newark, NJ hospital setting. Study design Pooled NAAT HIV-1 RNA testing was offered to emergency department patients and out-patients being screened for HIV antibodies by fingerstick-rapid HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled plasma samples were prepared and sent to the University of Washington where real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification was performed. Results Of 13,226 individuals screened, 6381 had rapid antibody testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all samples that screened positive for HIV-1 RNA were obtained from men. Conclusion HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits identification of recent infections. In Newark, pooled NAAT increased HIV-1 case detection and provided an opportunity to focus on treatment and prevention messages for those most at risk of transmitting infection. Although constrained by client willingness to participate in testing associated with a need to return to receive further results, use of pooled NAAT improved early infection sensitivity. PMID:23953941

  20. Humoral response to EBV is associated with cortical atrophy and lesion burden in patients with MS

    PubMed Central

    Cerza, Nicole; Hagemeier, Jesper; Carl, Ellen; Badgett, Darlene; Ramasamy, Deepa P.; Weinstock-Guttman, Bianca; Ramanathan, Murali

    2016-01-01

    Objective: Because dysregulated Epstein-Barr virus (EBV)-infected B cells may induce meningeal inflammation, which contributes to cortical pathology in multiple sclerosis (MS), we investigated associations between antibody responses to EBV and development of cortical pathology in MS. Methods: We included 539 patients with MS (369 with relapsing-remitting MS, 135 with secondary progressive MS, and 35 with primary progressive MS), 66 patients with clinically isolated syndrome (CIS), 63 patients with other neurologic diseases (OND), and 178 age- and sex-matched healthy controls (HC). All participants were scanned on 3T MRI. Serum samples were analyzed for IgG antibodies against EBV viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1), and their quartiles were determined on the whole study sample. Differences between the study groups were assessed using analysis of covariance adjusted for multiple comparisons. Results: More than 30% of patients with MS and CIS presented with the highest quartile of anti-EBV-VCA and -EBNA-1 status compared to ≤10% of HC (p < 0.001). The figures were 9 (14.3%) and 7 (12.3%) for patients with OND. Patients with MS with the highest quartile of anti-EBV-VCA showed significantly increased T2 lesion volume (p = 0.001), T1 lesion number (p = 0.002), and T1 lesion volume (p = 0.04) and decreased gray matter (p = 0.041) and cortical (p = 0.043) volumes compared to patients with MS with lower quartiles. No significant differences of MRI outcomes in patients with CIS, patients with OND, and HC with lower or highest quartiles of anti-EBV-VCA and -EBNA-1 were detected. Conclusions: Humoral response to anti-EBV-VCA and -EBNA-1 is associated with more advanced cortical atrophy, accumulation of chronic T1 black holes, and focal white matter lesions in patients with MS. PMID:26770996

  1. EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management.

    PubMed

    Castillo, Jorge J; Beltran, Brady E; Miranda, Roberto N; Young, Ken H; Chavez, Julio C; Sotomayor, Eduardo M

    2016-05-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL. Am. J. Hematol. 91:530-537, 2016. © 2016 Wiley Periodicals, Inc. PMID:27093913

  2. Does EBV alter the pathogenesis of malaria?

    PubMed

    Matar, C G; Jacobs, N T; Speck, S H; Lamb, T J; Moormann, A M

    2015-09-01

    Plasmodium falciparum infections have been implicated in immune deficiencies resulting in ineffective control of Epstein-Barr virus, thereby increasing the risk of endemic Burkitt lymphoma in children. However, the impact of Epstein-Barr virus infections on the development of immunity to P. falciparum has not been studied in depth. In this review, we examine novel findings from animal co-infection models and human immuno-epidemiologic studies to speculate on the impact of acute gammaherpesvirus co-infection on malarial disease severity. Children are often concurrently or sequentially infected with multiple pathogens, and this has implications for understanding the development of protective immunity as well as in the evaluation of vaccine efficacy. PMID:26121587

  3. Barr humbug: acute cerebellar ataxia due to Epstein-Barr virus.

    PubMed

    Davies, Benjamin; Machin, Nicholas; Lavin, Timothy; Ul Haq, Mian Ayaz

    2016-01-01

    Epstein-Barr virus (EBV) infection is associated with neurological sequellae, but rarely there is acute cerebellar ataxia (ACA) in an adult. We present a novel case of a 26-year-old man, who presented with ACA. He had normal MRI and CSF analysis. Serum testing confirmed active EBV. A course of oral prednisolone 1 mg/kg for 4 weeks, with a subsequent taper was started. He made a full recovery within 3 weeks of presentation. PMID:27558189

  4. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  5. Functional homology of gHs and gLs from EBV-related {gamma}-herpesviruses for EBV-induced membrane fusion

    SciTech Connect

    Omerovic, Jasmina; Longnecker, Richard . E-mail: r-longnecker@northwestern.edu

    2007-08-15

    Epstein-Barr virus (EBV) is a human {gamma}-herpesvirus that primarily infects B lymphocytes and epithelial cells. Entry of EBV into B cells requires the viral glycoproteins gp42, gH/gL and gB, while gp42 is not necessary for infection of epithelial cells. In EBV, gH and gL form two distinct complexes, a bipartite complex that contains only gH and gL, used for infection of epithelial cells, and a tripartite complex that additionally includes gp42, used for infection of B cells. The gH/gL complex is conserved within the herpesvirus family, but its exact role in entry and mechanism of fusion is not yet known. To understand more about the functionality of EBVgH/gL, we investigated the functional homology of gHs and gLs from human herpesvirus 8 (HHV8) and two primate (rhesus and marmoset) {gamma}-herpesviruses in EBV-mediated virus-free cell fusion assay. Overall, gHs and gLs from the more homologous primate herpesviruses were better at complementing EBV gH and gL in fusion than HHV8 gH and gL. Interestingly, marmoset gH was able to complement fusion with epithelial cells, but not B cells. Further investigation of this led to the discovery that EBVgH is the binding partner of gp42 in the tripartite complex and the absence of fusion with B cells in the presence of marmoset gH/gL is due to its inability to bind gp42.

  6. Acute disseminated encephalomyelitis associated with hepatitis A virus infection.

    PubMed

    Alehan, Füsun K; Kahveci, Suat; Uslu, Yasemin; Yildirim, Tülin; Yilmaz, Başak

    2004-06-01

    We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM. PMID:15186542

  7. Airway microbiota and acute respiratory infection in children.

    PubMed

    Hasegawa, Kohei; Camargo, Carlos A

    2015-01-01

    Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children. PMID:25961472

  8. Acute phase response to Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' infection in FIV-infected and non-FIV-infected cats.

    PubMed

    Korman, R M; Cerón, J J; Knowles, T G; Barker, E N; Eckersall, P D; Tasker, S

    2012-08-01

    The pathogenicity of Haemoplasma spp. in cats varies with 'Candidatus Mycoplasma haemominutum' (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7-14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16-44 pi to half of the Mhf-infected cats, and on days 49-77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species. PMID:22763129

  9. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    PubMed

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  10. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  11. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  12. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  13. Oritavancin for acute bacterial skin and skin structure infection

    PubMed Central

    Messina, Julia A.; Fowler, Vance G.; Corey, G. Ralph

    2015-01-01

    Introduction Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapidly bactericidal agent approved for the treatment of ABSSSI. Its prolonged half-life with one-time intravenous (IV) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of IV therapy. Areas covered This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/ pharmacokinetics, efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability. Expert Opinion If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged IV therapy, it will be sought as an alternative antibiotic therapy for ABSSSI. In addition, further clinical data demonstrating efficacy in gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market. PMID:25803197

  14. Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits.

    PubMed

    Koirala, Tirtha Raj; Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Tanaka, Takehiro; Oda, Wakako; Ichimura, Koichi; Ohara, Nobuya; Oka, Takashi; Yamada, Masao; Yoshino, Tadashi

    2004-04-01

    Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings. PMID:15255507

  15. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity

    PubMed Central

    Matar, Caline G.; Anthony, Neil R.; O’Flaherty, Brigid M.; Jacobs, Nathan T.; Priyamvada, Lalita; Engwerda, Christian R.; Speck, Samuel H.; Lamb, Tracey J.

    2015-01-01

    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. PMID:25996913

  16. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

    PubMed

    Matar, Caline G; Anthony, Neil R; O'Flaherty, Brigid M; Jacobs, Nathan T; Priyamvada, Lalita; Engwerda, Christian R; Speck, Samuel H; Lamb, Tracey J

    2015-05-01

    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. PMID:25996913

  17. KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

    SciTech Connect

    Bentz, Gretchen L.; Bheda-Malge, Anjali; Wang, Ling; Shackelford, Julia; Damania, Blossom; Pagano, Joseph S.

    2014-01-05

    Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies. - Highlights: • Infection of endothelial cells with KSHV induced UCH-L1 expression. • KSHV LANA is sufficient for the induction of uch-l1. • Co-infection with KSHV and EBV (observed in some PELs) results in the additive induction of uch-l1. • EBV LMP1 also induced UCH-L1 expression. • LANA- and LMP1-mediated activation of the uch-l1 promoter is in part through RBP-Jκ.

  18. Simultaneous detection of the two main proliferation driving EBV encoded proteins, EBNA-2 and LMP-1 in single B cells.

    PubMed

    Rasul, Abu E; Nagy, Noémi; Sohlberg, Ebba; Ádori, Mónika; Claesson, Hans-Erik; Klein, George; Klein, Eva

    2012-11-30

    Epstein Barr virus (EBV) is carried by almost all adults, mostly without clinical manifestations. Latent virus infection of B lymphocytes induces activation and proliferation that can be demonstrated in vitro. In healthy individuals, generation of EBV induced malignant proliferation is avoided by continuous immunological surveillance. The proliferation inducing set of the virally encoded genes is expressed exclusively in B cells in a defined differentiation window. It comprises nine EBV encoded nuclear proteins, EBNA 1-6, and three cell membrane associated proteins, LMP-1, 2A and 2B, designated as latency Type III. Outside this window the expression of the viral genes is limited. Healthy carriers harbor a low number of B lymphocytes in which the viral genome is either silent or expresses one virally encoded protein, EBNA-1, latency Type I. In addition, EBV genome carrying B cells can lack either EBNA-2 or LMP-1, latency Type IIa or Type IIb respectively. These cells have no inherent proliferation capacity. Detection of both EBNA-2 and LMP-1 can identify B cells with growth potential. We devised therefore a method for their simultaneous detection in cytospin deposited cell populations. Simultaneous detection of EBNA-2 and LMP-1 was reported earlier in tissues derived from infectious mononucleosis (IM), postransplantation lymphoproliferative disorders (PTLD) and from "humanized" mice infected with EBV. We show for the first time the occurrence of Type IIa and Type IIb cells in cord blood lymphocyte populations infected with EBV in vitro. Further, we confirm the variation of EBNA-2 and LMP-1 expression in several Type III lines and that they vary independently in individual cells. We visualize that in Type III LCL, induced for plasmacytoid differentiation by IL-21 treatment, EBV protein expression changes to Type IIa (EBNA-2 negative LMP-1 positive). We also show that when the proliferation of EBV infected cord blood lymphocyte culture is inhibited by the

  19. The role of viral agents in aetiopathogenesis of acute rheumatic fever.

    PubMed

    Olgunturk, Rana; Okur, Ilyas; Cirak, Meltem Y; Oguz, Ayse Deniz; Akalin, Nursel; Turet, Sevgi; Tunaoglu, Sedef

    2011-01-01

    The reason why abnormal immune response exists in acute rheumatic fever is not exactly explained. The influence of co-pathogens like certain viruses were mentioned regarding the initiation of the immunological reaction in acute rheumatic fever patients by several authors since 1970. This study was designed to find the role or effect of some viral infections in the development of rheumatic fever. In this study, 47 cases with acute rheumatic fever (acute rheumatic arthritis, acute rheumatic carditis, and chorea), 20 cases with chronic rheumatic fever, 20 cases with streptococcal pharyngitis, and 20 healthy age- and gender-matched control cases were involved. Serological and molecular tests were made including hepatitis B virus, hepatitis C virus, rubella virus, herpes simplex virus (HSV group 1), and Epstein-Barr virus (EBV). HBsAg, rubella IgM and EBV IgM positivity were not seen in any of patients with rheumatic fever. Although antiHBs seropositivity was higher in the control group, it was not statistically significant (p > 0.05). There was no difference in rubella IgG, HSV IgM seropositivity, either (p > 0.05). EBV DNA was searched by the polymerase chain reaction technique; due to the latent nature of the virus, no significant difference was found between the control group and the other groups (p > 0.05). In this study, no positive correlation could be found to support the synergism theories regarding the streptoccocus infection and viral infections in the development of acute rheumatic fever. Only EBV DNA positivity was found in all acute rheumatic fever cases but not in the control group may lead to further studies with larger series of patients. PMID:20401762

  20. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    PubMed Central

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  1. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

    PubMed

    Aliabadi, Negar; Messacar, Kevin; Pastula, Daniel M; Robinson, Christine C; Leshem, Eyal; Sejvar, James J; Nix, W Allan; Oberste, M Steven; Feikin, Daniel R; Dominguez, Samuel R

    2016-08-01

    During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  2. Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014

    PubMed Central

    Corman, Victor M.; Wong, Emily Y.M.; Tsang, Alan K.L.; Muth, Doreen; Lau, Susanna K. P.; Khazanehdari, Kamal; Zirkel, Florian; Ali, Mansoor; Nagy, Peter; Juhasz, Jutka; Wernery, Renate; Joseph, Sunitha; Syriac, Ginu; Elizabeth, Shyna K.; Patteril, Nissy Annie Georgy; Woo, Patrick C. Y.; Drosten, Christian

    2015-01-01

    Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother–calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk. PMID:25989145

  3. Effect of a Clostridium difficile Infection Prevention Initiative in Veterans Affairs Acute Care Facilities.

    PubMed

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A

    2016-06-01

    Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID:26864803

  4. SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections.

    PubMed Central

    Johnson, L L

    1992-01-01

    Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients. Images PMID:1500181

  5. Epstein-Barr virus-encoded small RNAs (EBERs) are present in fractions related to exosomes released by EBV-transformed cells.

    PubMed

    Ahmed, Waqar; Philip, Pretty S; Tariq, Saeed; Khan, Gulfaraz

    2014-01-01

    Epstein-Barr virus (EBV) is an oncogenic herpesvirus associated with a number of human malignancies of epithelial and lymphoid origin. However, the mechanism of oncogenesis is unclear. A number of viral products, including EBV latent proteins and non-protein coding RNAs have been implicated. Recently it was reported that EBV-encoded small RNAs (EBERs) are released from EBV infected cells and they can induce biological changes in cells via signaling from toll-like receptor 3. Here, we investigated if these abundantly expressed non-protein coding EBV RNAs (EBER-1 and EBER-2) are excreted from infected cells in exosomal fractions. Using differential ultracentrifugation we isolated exosomes from three EBV positive cell lines (B95-8, EBV-LCL, BL30-B95-8), one EBER-1 transfected cell line (293T-pHEBo-E1) and two EBV-negative cell lines (BL30, 293T-pHEBo). The identity of purified exosomes was determined by electron microscopy and western blotting for CD63. The presence of EBERs in cells, culture supernatants and purified exosomal fractions was determined using RT-PCR and confirmed by sequencing. Purified exosomal fractions were also tested for the presence of the EBER-1-binding protein La, using western blotting. Both EBER-1 and EBER-2 were found to be present not only in the culture supernatants, but also in the purified exosome fractions of all EBV-infected cell lines. EBER-1 could also be detected in exosomal fractions from EBER-1 transfected 293T cells whilst the fractions from vector only transfectants were clearly negative. Furthermore, purified exosomal fractions also contained the EBER-binding protein (La), supporting the notion that EBERs are most probably released from EBV infected cells in the form of EBER-La complex in exosomes. PMID:24896633

  6. NCI International EBV-Gastric Cancer Consortium

    Cancer.gov

    A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

  7. Multiple Epstein-Barr virus infections in healthy individuals

    NASA Technical Reports Server (NTRS)

    Walling, Dennis M.; Brown, Abigail L.; Etienne, Wiguins; Keitel, Wendy A.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2003-01-01

    We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

  8. Acute cholecystitis associated with infection of Enterobacteriaceae from gut microbiota.

    PubMed

    Liu, J; Yan, Q; Luo, F; Shang, D; Wu, D; Zhang, H; Shang, X; Kang, X; Abdo, M; Liu, B; Ma, Y; Xin, Y

    2015-09-01

    Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the biliary system and the gut, the aims of this study were to characterize and determine the influence of gut microbiota on AC, to detect the pathogenic microorganism in the biliary system, and to explore the relationship between the gut and bile microbiota of patients with AC. A total of 185 713 high-quality sequence reads were generated from the faecal samples of 15 patients and 13 healthy controls by 16S rRNA gene pyrosequencing. Patients' samples were significantly enriched in Akkermansia, Enterobacter and Escherichia/Shigella group. The healthy controls, however, showed significant enrichment of Clostridiales, Coprococcus, Coprobacillaceae, Paraprevotella, Turicibacter and TM7-3 in their faecal samples. Escherichia coli was the main biliary pathogenic microorganism, among others such as Klebsiella spp., Clostridium perfringens, Citrobacter freundii and Enterobacter cloacae in the bile of the patients. Additionally, the amount of bile endotoxin significantly correlated with the number of Enterobacteriaceae, especially E. coli. Our data indicate that Enterobacteriaceae might play essential role in the pathogenesis and/or progress of AC. This was verified in an in vivo model using a pathogenic E. coli isolated from one of the patients in guinea pigs and observed marked gallbladder inflammation and morphologic changes. This study thus provides insight which could be useful for the prevention, diagnosis and treatment of AC and related diseases by controlling the growth of Enterobacteriaceae to alleviate the infection. PMID:26025761

  9. Incubation periods of acute respiratory viral infections: a systematic review

    PubMed Central

    Lessler, Justin; Reich, Nicholas G; Brookmeyer, Ron; Perl, Trish M; Nelson, Kenrad E; Cummings, Derek A T

    2015-01-01

    Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications. PMID:19393959

  10. Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections

    PubMed Central

    Obasi, Chidi N.; Barrett, Bruce; Brown, Roger; Vrtis, Rose; Barlow, Shari; Muller, Daniel; Gern, James

    2013-01-01

    Objectives The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. Methods Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. Results Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. Conclusion Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. Summary We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms. PMID:24211414

  11. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. Profiling Acute Respiratory Tract Infections in Children from Assam, India

    PubMed Central

    Islam, Farzana; Sarma, Ratna; Debroy, Arup; Kar, Sumit; Pal, Ranabir

    2013-01-01

    Background: Acute respiratory infections (ARI) are leading global cause of under-five mortality and morbidity. Objective: To elicit the prevalence and risk factors associated with ARI among under-five children. Materials and Methods: A community-based cross-sectional study was undertaken in 21 registered urban slums of Guwahati in Assam to determine the prevalence and risk factors associated with ARI among 370 under-five children from 184 households and 370 families. Results: The prevalence of ARI was found to be 26.22%; infants and female children were more affected. Majority of the ARI cases were from nuclear families (84.54%), living in kutcha houses (90.72%) with inadequate ventilation (84.54%), overcrowded living condition (81.44%), with kitchen attached to the living room (65.98%) and using biomass fuel for cooking (89.69%). ARI was significantly associated with ventilation, location of kitchen in household; presence of overcrowding, nutritional status, and primary immunization status also had impacts on ARI. Conclusion: The present study had identified a high prevalence of the disease among under-fives. It also pointed out various socio-demographic, nutritional, and environmental modifiable risk factors which can be tackled by effective education of the community. PMID:23599611

  13. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  14. Nef gene evolution from a single transmitted strain in acute SIV infection

    PubMed Central

    Bimber, Benjamin N; Chugh, Pauline; Giorgi, Elena E; Kim, Baek; Almudevar, Anthony L; Dewhurst, Stephen; O'Connor, David H; Lee, Ha Youn

    2009-01-01

    Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC) simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate. PMID:19505314

  15. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.

    PubMed

    Padoan, Rita; Poli, Piercarlo; Colombrita, Domenico; Borghi, Elisa; Timpano, Silviana; Berlucchi, Marco

    2016-06-01

    Fungi are known pathogens in cystic fibrosis patients. A boy with cystic fibrosis boy presented with acute respiratory distress. Bronchoscopy showed airways obstruction by mucus plugs and bronchial casts. Scedosporium apiospermum was identified as the only pathogen. Bronchoalveolar lavage successfully resolved the acute obstruction. Plastic bronchitis is a new clinical picture of acute Scedosporium endobronchial colonization in cystic fibrosis patients. PMID:26967814

  16. Clinical and laboratory predictive markers for acute dengue infection

    PubMed Central

    2013-01-01

    Background Early diagnosis of dengue virus infection during the febrile stage is essential for adjusting appropriate management. This study is to identify the predictive markers of clinical and laboratory findings in the acute stage of dengue infection during a major outbreak of dengue virus type 1 that occurred in southern Taiwan during 2007. A retrospective, hospital-based study was conducted at a university hospital in southern Taiwan from January to December, 2007. Patient who was reported for clinically suspected dengue infection was enrolled. Laboratory-positive dengue cases are confirmed by enzyme-linked immunosorbent assay of specific dengue IgM, fourfold increase of dengue-specific IgG titers in convalescent serum, or by reverse transcription-polymerase chain reaction (RT-PCR) of dengue virus. Results The suspected dengue cases consist of 100 children (≤ 18 years) and 481 adults. Among the 581 patients, 67 (67%) children and 309 (64.2%) adults were laboratory-confirmed. Patients who had laboratory indeterminate were excluded. Most cases were uncomplicated and 3.8% of children and 2.9% of adults developed dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS). The overall mortality rate in those with DHF/DSS was 7.1%, and the average duration of hospitalization was 20 days. The most common symptoms/signs at admission were myalgia (46.8%), petechiae (36.9%) and nausea/vomiting (33.5%). The most notable laboratory findings included leukopenia (2966 ± 1896/cmm), thrombocytopenia (102 ± 45 × 103/cmm), prolonged activated partial thromboplastin time (aPTT) (45 ± 10 s), and elevated serum levels of aminotransferase (AST, 166 ± 208 U/L; ALT, 82 ± 103 U/L) and low C - reactive protein (CRP) (6 ± 11 mg/L). Based on the clinical features for predicting laboratory-confirmed dengue infection, the sensitivities of typical rash, myalgia, and positive tourniquet test are 59.2%, 46.8%, and 34.2%, while the specificities for

  17. Disseminated Neocosmospora vasinfecta infection in a patient with acute nonlymphocytic leukemia.

    PubMed Central

    Cornely, O. A.; Chemnitz, J.; Brochhagen, H. G.; Lemmer, K.; Schütt, H.; Söhngen, D.; Staib, P.; Wickenhauser, C.; Diehl, V.; Tintelnot, K.

    2001-01-01

    We report Neocosmospora vasinfecta infection following chemotherapy for acute nonlymphocytic leukemia. N. vasinfecta, a plant pathogen, was identified by culture and genetic sequencing. Susceptibility testing revealed in vitro resistance for common antifungals. PMID:11266308

  18. Changes in ovarian follicles following acute infection with bovine viral diarrhea virus.

    PubMed

    Grooms, D L; Brock, K V; Pate, J L; Day, M L

    1998-02-01

    Bovine viral diarrhea virus (BVDV) has been associated with several reproductive problems in cattle, including poor fertility, early embryonic deaths, abortion and congenital anomalies. Little is known about the cause of poor fertility in cows acutely infected with BVDV. The purpose of this study was to identify changes in ovarian function following acute infection with noncytopathic BVDV. The ovaries of 5 BVDV sero-negative and virus-negative pubertal heifers were monitored daily for 4 consecutive estrous cycles. The position and diameter of all follicles (> 5 mm) and luteal structures were recorded. Daily plasma samples were collected to measure peripheral progesterone and estradiol levels. Each heifer was infected intranasally with noncytopathic BVDV following ovulation of the second estrous cycle. The maximum diameter and growth rate of dominant anovulatory and ovulatory follicles were significantly reduced following acute BVDV infection. Similarly, the number of subordinate follicles associated with both the anovulatory and ovulatory follicle was reduced following infection. There were no significant differences in other follicle or luteal dynamic parameters or in peripheral progesterone or estradiol levels. Ovarian follicular growth was different during the first 2 estrous cycles following acute infection with BVDV when compared with the 2 estrous cycles preceding infection. These differences may be important in explaining reduced fertility in herds with acute BVDV infection. PMID:10732038

  19. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  20. Acute Hepatitis as a Manifestation of Parvovirus B19 Infection

    PubMed Central

    Hatakka, Aleisha; Klein, Julianne; He, Runtao; Piper, Jessica; Tam, Edward; Walkty, Andrew

    2011-01-01

    There are few reports in the literature of hepatitis as a manifestation of parvovirus B19 infection. We describe a case of parvovirus B19-associated acute hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19 infection should be considered in the differential diagnosis of patients presenting with acute hepatitis. PMID:21734024

  1. Varicella Zoster Infection: A Rare Cause of Abdominal Pain Mimicking Acute Abdomen

    PubMed Central

    Olmez, Deniz; Boz, Alper; Erkan, Nazif

    2009-01-01

    Varicella zoster is an acute viral infection that results from reactivation of a latent varicella zoster virus. It usually occurs in adult population and immune compromised patients. It rarely occurs in healthy children. Here we present a 14 years old male with varicella zoster that had abdominal pain mimicking acute abdomen to alert others who are consulted for the differentiation of acute abdomen and others who may be consulted for pain management. Keywords Varicella zoster; Abdominal pain PMID:22461879

  2. Nonmuscle myosin heavy chain IIA mediates Epstein–Barr virus infection of nasopharyngeal epithelial cells

    PubMed Central

    Xiong, Dan; Du, Yong; Wang, Hong-Bo; Zhao, Bo; Zhang, Hua; Li, Yan; Hu, Li-Juan; Cao, Jing-Yan; Zhong, Qian; Liu, Wan-Li; Li, Man-Zhi; Zhu, Xiao-Feng; Tsao, Sai Wah; Hutt-Fletcher, Lindsey M.; Song, Erwei; Zeng, Yi-Xin; Kieff, Elliott; Zeng, Mu-Sheng

    2015-01-01

    EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC). Although the mechanisms by which EBV infects B lymphocytes have been extensively studied, investigation of the mechanisms by which EBV infects nasopharyngeal epithelial cells (NPECs) has only recently been enabled by the successful growth of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in vitro and the discovery that neuropilin 1 expression positively affects EBV glycoprotein B (gB)-mediated infection and tyrosine kinase activations in enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%), close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC protein important for efficient EBV infection. EBV gH/gL specifically interacted with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was significantly reduced by NMHC-IIA siRNA knock-down. NMHC-IIA antisera also efficiently blocked EBV infection. These data indicate that NMHC-IIA is an important factor for EBV NPEC infection. PMID:26290577

  3. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  4. Chlamydia trachomatis Antigens Recognized by Women With Tubal Factor Infertility, Normal Fertility, and Acute Infection

    PubMed Central

    Budrys, Nicole M.; Gong, Siqi; Rodgers, Allison K.; Wang, Jie; Louden, Christopher; Shain, Rochelle; Schenken, Robert S.; Zhong, Guangming

    2015-01-01

    Objective To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. Methods A C. trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C. trachomatis infection. Results Thirteen immunodominant antigens reacted with 50% or more sera from all women (N=73). Six C. trachomatis antigens were uniquely recognized by women diagnosed with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.91–1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C. trachomatis-exposed women with a detection sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.95–1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. Conclusion A sequential screening of antibodies against panels of C. trachomatis antigens can be used to identify women with tubal factor infertility and acute C. trachomatis infection. PMID:22525912

  5. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    PubMed Central

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M.; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14–18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14–18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues. PMID:19236838

  6. c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1.

    PubMed Central

    Polack, A; Hörtnagel, K; Pajic, A; Christoph, B; Baier, B; Falk, M; Mautner, J; Geltinger, C; Bornkamm, G W; Kempkes, B

    1996-01-01

    Two genetic events contribute to the development of endemic Burkitt lymphoma (BL) infection of B lymphocytes with Epstein-Barr virus (EBV) and the activation of the protooncogene c-myc through chromosomal translocation. The viral genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for transformation of primary human B cells by EBV in vitro; however, these genes are not expressed in BL cells in vivo. To address the question whether c-myc activation might abrogate the requirement of the EBNA2 and LMP1 function, we have introduced an activated c-myc gene into an EBV-transformed cell line in which EBNA2 was rendered estrogen-dependent through fusion with the hormone binding domain of the estrogen receptor. The c-myc gene was placed under the control of regulatory elements of the immunoglobulin kappa locus composed a matrix attachment region, the intron enhancer, and the 3' enhancer. We show here that transfection of a c-myc expression plasmid followed by selection for high MYC expression is capable of inducing continuous proliferation of these cells in the absence of functional EBNA2 and LMP1. c-myc-induced hormone-independent proliferation was associated with a dramatic change in the growth behavior as well as cell surface marker expression of these cells. The typical lymphoblastoid morphology and phenotype of EBV-transformed cells completely changed into that of BL cells in vivo. We conclude that the phenotype of BL cells reflects the expression pattern of viral and cellular genes rather than its germinal center origin. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8816814

  7. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  8. Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series

    PubMed Central

    Panichsillapakit, Theppharit; Patel, Derek; Santangelo, Joanne; Richman, Douglas D.; Little, Susan J.; Smith, Davey M.

    2016-01-01

    Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract. PMID:26925432

  9. BOVINE VIRAL DIARRHEA VIRUS PERSISTENTLY INFECTED AND ACUTELY INFECTED CALVES: ASSAYS FOR VIRAL INFECTIVITY, POLYMERASE CHAIN REACTION ANALYSIS, AND ANTIGEN DETECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous assays for bovine viral diarrhea virus (BVDV) detecting infectious virus, nucleic material, and antigen. Persistently infected (PI) and acutely/transiently infected calves with BVDV represent two different manifestations. Diagnostic test results impact on differentiation of PI o...

  10. Chronic Physical Stress Does Not Interact with Epstein-Barr Virus (EBV)-Encoded Dutpase to Alter the Sickness Response

    PubMed Central

    Weil, Zachary M.; Abi Salloum, Bachir; Ariza, Maria Eugenia; Williams, Marshall; Reader, Brenda; Glaser, Ronald; Sheridan, John; Nelson, Randy J.

    2016-01-01

    Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in combination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions remains unspecified. In this study, we seek to determine the interaction of chronic physical (swim) stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis mice receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 min of swim stress each day for 14 days or left unmanipulated. On the final evening of injections mice undergo behavioral testing. EBV-encoded dUTPase injection alone produces some sickness behaviors. The physical swimming stress does not alter the sickness response. PMID:27175311

  11. Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort.

    PubMed

    Ramien, Caren; Pachnio, Annette; Sisay, Sofia; Begum, Jusnara; Leese, Alison; Disanto, Giulio; Kuhle, Jens; Giovannoni, Gavin; Rickinson, Alan; Ramagopalan, Sreeram V; Moss, Paul; Meier, Ute-Christiane

    2014-05-01

    Late Epstein-Barr virus infection and hypovitaminosis-D as environmental risk factors in the pathogenesis of multiple sclerosis are gaining great interest. We, therefore, tested for in-vivo interdependence between Epstein-Barr-virus (EBV)-status and 25-hydroxyvitamin D3 (25(OH)D3) -level in healthy young individuals from a United Kingdom (UK) autumn cohort. EBV-load was measured by quantitative polymerase chain reaction and 25(OH)D3 levels by isotope-dilution liquid chromatography-tandem mass spectrometry. This young, healthy UK autumn cohort showed surprisingly low levels of 25(OH)D3 (mean value: 40.5 nmol/L ± 5.02). Furthermore, we found that low 25(OH)D3 levels did not impact on EBV load and anti-EBV nuclear antigen-1 (EBNA-1) titers. However, we observed a correlation between EBV load and EBNA-1 titers. These observations should be of value in the study of the potential relationship between hypovitaminosis-D and EBV-status in the pathophysiology of multiple sclerosis. PMID:24192216

  12. Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa

    PubMed Central

    Adjei, Andrew A; Armah, Henry B; Gbagbo, Foster; Boamah, Isaac; Adu-Gyamfi, Clement; Asare, Isaac

    2008-01-01

    Background Human herpesvirus 8 (HHV-8), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are prevalent in Africa, but less common elsewhere and the modes of transmission are still subject to debate. Generally, they rarely cause disease in the immunocompetent host but are highly oncogenic when associated with immunosuppression. Although the high prevalence of HHV-8, CMV and EBV has been well documented in Africa, such data are sparse from Ghana. Methods Serum samples from 3275 HIV-seronegative healthy blood donors and 250 HIV-AIDS patients were tested for antibodies specific for HHV-8, CMV and EBV by IgG ELISA assays. Differences in seropositivity rates by gender and age were evaluated using the Chi-square test with Yates correction. Results Of the 3275 HIV-seronegative healthy blood donors tested, 2573 (78.6%) were males and 702 (21.4%) were females, with ages ranging from 18 to 65 years (median 32.6; mean 31.2; mode 30). Of the 250 HIV-AIDS patients tested, 140 (56%) were males and 110 (44%) were females, with ages ranging from 17 to 64 years (median 30.8; mean 30.3; mode 28). Among the HIV-seronegative healthy blood donors, overall seroprevalence of HHV-8, CMV and EBV was 23.7%, 77.6% and 20.0%, respectively. Among the HIV-AIDS patients, overall seroprevalence of HHV-8, CMV and EBV was 65.6%, 59.2% and 87.2%, respectively. The seroprevalence of HHV-8 (p < 0.005) and EBV (p < 0.001) was statistically significantly higher in HIV-AIDS patients compared to HIV-seronegative healthy blood donors. There was no statistically significant difference (p = 0.24) between CMV seroprevalence in HIV-AIDS patients and HIV-seronegative healthy blood donors. Age and gender were not independent determinants (p > 0.05) for all three infections among HIV-seronegative healthy blood donors and HIV-AIDS patients in Ghana. Conclusion The results presented herein indicate that HHV-8, CMV and EBV infections are hyperendemic in both HIV-seronegative and HIV-seropositive Ghanaians, and

  13. Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan.

    PubMed

    Kjaergaard, Astrid B; Carr, Anthony P; Gaunt, M Casey

    2016-09-01

    Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea. PMID:27587889

  14. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  15. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

    PubMed

    Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  16. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

    PubMed Central

    O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  17. Identification of GLA/SE as an effective adjuvant for the induction of robust humoral and cell-mediated immune responses to EBV-gp350 in mice and rabbits.

    PubMed

    Heeke, Darren S; Lin, Rui; Rao, Eileen; Woo, Jennifer C; McCarthy, Michael P; Marshall, Jason D

    2016-05-17

    Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic and may result in mild flu-like symptoms, but exposure during adolescence and young adulthood can lead to acute infectious mononucleosis (AIM) with a pathology characterized by swollen lymph nodes, sore throat, and severe fatigue lasting weeks or months. A vaccine targeting the envelope glycoprotein gp350 adjuvanted with aluminum hydroxide complexed with the TLR4 agonist monophosphoryl lipid A (MPLA) achieved a 78% reduction in AIM incidence in a small phase II trial of college-age individuals, but development of this vaccine was halted by the manufacturer. Here, we report the evaluation in mice and rabbits of an EBV-gp350 vaccine combined with an adjuvant composed of the synthetic TLR4 agonist glucopyranosyl lipid A (GLA) integrated into stable emulsion (SE). In mice, GLA/SE-adjuvanted gp350 generated high IgG titers (both IgG1 and IgG2a/c subtypes), elevated EBV-neutralizing antibody titers, and robust poly-functional anti-gp350 CD4(+) T cell responses. In addition, GLA/SE routinely demonstrated superior performance over aluminum hydroxide in all immunological readouts, including induction of durable neutralizing antibody titers out to at least 1 year post-vaccination. Both components of the GLA/SE adjuvant were found to be required to get optimal responses in both arms of the immune response: specifically, SE for neutralizing antibodies and GLA for induction of T cell responses. Furthermore, this vaccine also elicited high neutralizing antibody titers in a second species, rabbit. These promising results suggest that clinical development of a vaccine comprised of EBV-gp350 plus GLA/SE has the potential to prevent AIM in post-adolescents. PMID:27085175

  18. HLA Allele E*01:01 Is Associated with a Reduced Risk of EBV-Related Classical Hodgkin Lymphoma Independently of HLA-A*01/*02

    PubMed Central

    Martín, Paloma; Krsnik, Isabel; Navarro, Belen; Provencio, Mariano; García, Juan F.; Bellas, Carmen; Vilches, Carlos; Gomez-Lozano, Natalia

    2015-01-01

    Background An inefficient immune response against Epstein-Barr virus (EBV) infection is related to the pathogenesis of a subgroup of classical Hodgkin lymphomas (cHL). Some EBV immune-evasion mechanisms target HLA presentation, including the non-classical HLA-E molecule. HLA-E can be recognized by T cells via the TCR, and it also regulates natural killer (NK) cell signaling through the inhibitory CD94/NKG2A receptor. Some evidences indicate that EBV-infected B-cells promote the proliferation of NK subsets bearing CD94/NKG2A, suggesting a relevant function of these cells in EBV control. Variations in CD94/NKG2A-HLA-E interactions could affect NK cell-mediated immunity and, consequently, play a role in EBV-driven transformation and lymphomagenesis. The two most common HLA-E alleles, E*01:01 and E*01:03, differ by a single amino acid change that modifies the molecule function. We hypothesized that the functional differences in these variants might participate in the pathogenicity of EBV. Aim We studied two series of cHL patients, both with EBV-positive and-negative cases, and a cohort of unrelated controls, to assess the impact of HLA-E variants on EBV-related cHL susceptibility. Results We found that the genotypes with at least one copy of E*01:01 (i.e., E*01:01 homozygous and heterozygous) were underrepresented among cHL patients from both series compared to controls (72.6% and 71.6% vs 83%, p = 0.001). After stratification by EBV status, we found low rates of E*01:01-carriers mainly among EBV-positive cases (67.6%). These reduced frequencies are seen independently of other factors such as age, gender, HLA-A*01 and HLA-A*02, HLA alleles positively and negatively associated with the disease (adjusted OR = 0.4, p = 0.001). Furthermore, alleles from both HLA loci exert a cumulative effect on EBV-associated cHL susceptibility. Conclusions These results indicate that E*01:01 is a novel protective genetic factor in EBV-associated cHL and support a role for HLA

  19. Epstein-Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in EBV-positive B-lymphoma cells through up-regulation of survivin

    SciTech Connect

    Lu Jie; Murakami, Masanao; Verma, Subhash C.; Cai Qiliang; Haldar, Sabyasachi; Kaul, Rajeev; Wasik, Mariusz A.; Middeldorp, Jaap; Robertson, Erle S.

    2011-02-05

    Resistance to apoptosis is an important component of the overall mechanism which drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which preferentially establishes latent infection in viral infected B-lymphocytes. EBNA1 is typically expressed in most forms of EBV-positive malignancies and is important for replication of the latent episome in concert with replication of the host cells. Here, we investigate the effects of EBNA1 on survivin up-regulation in EBV-infected human B-lymphoma cells. We present evidence which demonstrates that EBNA1 forms a complex with Sp1 or Sp1-like proteins bound to their cis-element at the survivin promoter. This enhances the activity of the complex and up-regulates survivin. Knockdown of survivin and EBNA1 showed enhanced apoptosis in infected cells and thus supports a role for EBNA1 in suppressing apoptosis in EBV-infected cells. Here, we suggest that EBV encoded EBNA1 can contribute to the oncogenic process by up-regulating the apoptosis suppressor protein, survivin in EBV-associated B-lymphoma cells.

  20. Acute hepatitis C virus infection related to capillary blood glucose meter

    PubMed Central

    Inayat, Faisal; Rai, Aitzaz BinSultan

    2016-01-01

    Hepatitis C virus (HCV) infects an estimated 130-150 million people worldwide, becoming the major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation. There are various preventable modes of transmission of HCV infection, including needlestick and sharps injuries. However, HCV infection secondary to needlestick injury by a capillary blood glucose meter (CBGM) lancet has not been previously well reported. We describe an unusual case of a 25-year-old male medical student, acquiring acute HCV infection with a lancing device of CBGM. The source patient was a 54-year-old diabetic male with positive anti-HCV test results. In our patient, after 3 months of initial exposure, a standard set of investigations confirmed the diagnosis of acute HCV infection with the same genotype (3a) as the source. The CBGM, as in our case, may have a role in the transmission of HCV infection warranting radical advancements in diabetes screening and monitoring technology. PMID:26739982

  1. Impact of early cART in the gut during acute HIV infection

    PubMed Central

    Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing-Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Sereti, Irini; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat; Estes, Jacob D.

    2016-01-01

    Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART. PMID:27446990

  2. Acute Disseminated Encephalomyelitis After Plasmodium Vivax Infection: Case Report and Review of Literature

    PubMed Central

    Sidhu, Jasmeet; Maheshwari, Anu; Gupta, Raju; Devgan, Veena

    2015-01-01

    Acute demyelinating encephalomyelitis (ADEM) usually occurs after viral infections or vaccination. Its occurrence after Plasmodium vivax infection is extremely uncommon. We report the case of an 8-year-old girl who had choreo-athetoid movements and ataxia after recovery from P.vivax infection. Diagnosis of ADEM was made on the basis of magnetic resonance imaging findings. The child responded to corticosteroids with complete neurological recovery. PMID:26266032

  3. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    PubMed

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. PMID:26401005

  4. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    PubMed Central

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-01-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  5. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia.

    PubMed

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-03-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  6. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  7. Dissecting the contribution of EBNA3C domains important for EBV-induced B-cell growth and proliferation

    PubMed Central

    Lu, Jie; Prasad Aj, Mahadesh; Banerjee, Shuvomoy; Robertson, Erle S.

    2015-01-01

    Epstein-Barr virus (EBV) is an oncogenic gammaherpes virus which is linked to pathogenesis of several human lymphatic malignancies. The EBV essential latent antigen EBNA3C is critical for efficient conversion of primary human B-lymphocytes to lymphoblastic cell lines and for continued LCL growth. EBNA3C, an EBV latent antigen with oncogenic potential can bind and regulate the functions of a wide range of cellular transcription factors. In our current reverse genetics study, we deleted the full length EBNA3C, and independently the RBP-Jκ and Nm23-H1 binding sites within EBNA3C using BACmid recombinant engineering methodology. Our experiments demonstrated that deletion of the EBV EBNA3C open reading frame (ORF) and more specifically the residues 621–675 which binds Nm23H1 and SUMO-1 showed a significant reduction in the ability of the cells to proliferate. Furthermore, they exhibited lower infectivity of human peripheral blood mononuclear cells (PBMCs). We also showed that recombinant EBV with deletions of the EBNA3C ORF, as well as a recombinant with residues 621–675 within EBNA3C ORF deleted had diminished abilities to activate CD40. Our study also revealed that the full length (1–992) and 621–675 aa deletions of EBNA3C when compared to wild type EBV infected PBMCs had differential expression patterns for the phosphorylation of MAP kinases specifically p38, JNK and ERK. Regulation of β-catenin also differed among wild type and EBNA3C deleted mutants. These temporal differences in signaling activities of these recombinant viruses in PBMCs is likely important in defining their functional importance in EBV-mediated B-cell transformation. PMID:26336822

  8. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  9. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  10. PKC theta and p38 MAPK activate the EBV lytic cycle through autophagy induction.

    PubMed

    Gonnella, Roberta; Granato, Marisa; Farina, Antonella; Santarelli, Roberta; Faggioni, Alberto; Cirone, Mara

    2015-07-01

    PKC activation by combining TPA with sodium butyrate (T/B) represents the most effective and widely used strategy to induce the Epstein-Barr virus (EBV) lytic cycle. The results obtained in this study show that novel PKCθ is involved in such process and that it acts through the activation of p38 MAPK and autophagy induction. Autophagy, a mechanism of cellular defense in stressful conditions, is manipulated by EBV to enhance viral replication. Besides promoting the EBV lytic cycle, the activation of p38 and autophagy resulted in a pro-survival effect, as indicated by p38 or ATG5 knocking down experiments. However, this pro-survival role was counteracted by a pro-death activity of PKCθ, due to the dephosphorylation of AKT. In conclusion, this study reports, for the first time, that T/B activates a PKCθ-p38 MAPK axis in EBV infected B cells, that promotes the viral lytic cycle and cell survival and dephosphorylates AKT, balancing cell life and cell death. PMID:25827954

  11. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  12. Epigenetic silencing of tumor suppressor genes during in vitro Epstein–Barr virus infection

    PubMed Central

    Saha, Abhik; Jha, Hem C.; Upadhyay, Santosh K.; Robertson, Erle S.

    2015-01-01

    DNA-methylation at CpG islands is one of the prevalent epigenetic alterations regulating gene-expression patterns in mammalian cells. Hypo- or hypermethylation-mediated oncogene activation, or tumor suppressor gene (TSG) silencing mechanisms, widely contribute to the development of multiple human cancers. Furthermore, oncogenic viruses, including Epstein–Barr virus (EBV)-associated human cancers, were also shown to be influenced by epigenetic modifications on the viral and cellular genomes in the infected cells. We investigated EBV infection of resting B lymphocytes, which leads to continuously proliferating lymphoblastoid cell lines through examination of the expression pattern of a comprehensive panel of TSGs and the epigenetic modifications, particularly methylation of their regulatory sequences. EBV infection of primary B lymphocytes resulted in global transcriptional repression of TSGs through engagement of hypermethylation. Therefore, CpG methylation profiles of TSGs may be used as a prognostic marker as well as development of potential therapeutic strategies for controlling acute infection and EBV-associated B-cell lymphomas. PMID:26324942

  13. Toward an HIV Cure Based on Targeted Killing of Infected Cells: Different Approaches Against Acute Versus Chronic Infection

    PubMed Central

    Dey, Barna; Berger, Edward A.

    2015-01-01

    Purpose of review Current regimens of combination antiretroviral therapy (cART) offer effective control of HIV infection, with maintenance of immune health and near-normal life expectancy. What will it take to progress beyond the status quo, whereby infectious virus can be eradicated (a “sterilizing cure”) or fully controlled without the need for ongoing cART (a “functional cure”)? Recent findings Based on therapeutic advances in the cancer field, we propose that targeted cytotoxic therapy to kill HIV-infected cells represents a logical complement to cART for achieving an HIV cure. This concept is based on the fact that cART effectively blocks replication of the virus, but does not eliminate cells that are already infected; targeted cytotoxic therapy would contribute precisely this missing component. We suggest that different modalities are suited for curing primary acute versus established chronic infection. For acute infection, relatively short-acting potent agents such as recombinant immunotoxins might prove sufficient for HIV eradication whereas for chronic infection, a long-lasting (lifelong?) modality is required to maintain full virus control, as might be achieved with genetically modified autologous T cells. Summary We present perspectives for complementing cART with targeted cytotoxic therapy whereby HIV infection is either eradicated or fully controlled, thereby eliminating the need for lifelong antiretroviral therapy. PMID:25710815

  14. Parvovirus B19V infection in Israel: prevalence and occurrence of acute infection between 2008 and 2013.

    PubMed

    Mor, O; Ofir, I; Pavel, R; Bassal, R; Kra-Oz, Z; Cohen, D; Shohat, T; Mendelson, E

    2016-01-01

    Differences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infections have been documented around the world. This study was conducted to estimate the seroprevalence of anti-parvovirus B19V IgG antibodies in the Israeli population and to assess the pattern of acute infection based on data from two laboratories in Israel. The overall IgG prevalence in the 1008 representative sera samples was 61·4% and the age-adjusted prevalence rate was 58·2%. Seropositivity was significantly associated with age, ranging from 25·7% in children aged 20 years. While no significant differences in seropositivity were detected between sexes and population groups, significantly lower seroprevalence was observed in older Jews born in Africa or Asia. Acute infection rates of 4·1% (234 cases) were found based on the positive IgM results identified in samples from 5663 individuals collected between 2008 and 2013. Annual peaks of infection were observed in 2008 and 2011-2012 and major seasonal peak of B19V IgM positivity was identified in June each year. The number of requests for B19V serology was significantly higher for women aged 20-39 years while the majority IgM-positive cases were identified in young children. With more than 30% of the adult population being susceptible to B19V infection, monitoring B19V status should be considered in specific risk groups such as pregnant women. PMID:25990962

  15. Hospital Epidemiology and Infection Control in Acute-Care Settings

    PubMed Central

    Sydnor, Emily R. M.; Perl, Trish M.

    2011-01-01

    Summary: Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program. PMID:21233510

  16. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

  17. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection

    PubMed Central

    2005-01-01

    Background Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. Case report We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. Conclusion This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis. PMID:16164756

  18. AraC-Type Regulator Rsp Adapts Staphylococcus aureus Gene Expression to Acute Infection.

    PubMed

    Li, Tianming; He, Lei; Song, Yan; Villaruz, Amer E; Joo, Hwang-Soo; Liu, Qian; Zhu, Yuanjun; Wang, Yanan; Qin, Juanxiu; Otto, Michael; Li, Min

    2016-03-01

    Staphylococcus aureus is an important human pathogen that can cause two categories of severe infections. Acute infections are characterized by pronounced toxin production, while chronic infections often involve biofilm formation. However, it is poorly understood how S. aureus controls the expression of genes associated with acute versus biofilm-associated virulence. We here identified an AraC-type transcriptional regulator, Rsp, that promotes the production of key toxins while repressing major biofilm-associated genes and biofilm formation. Genome-wide transcriptional analysis and modeling of regulatory networks indicated that upregulation of the accessory gene regulator (Agr) and downregulation of the ica operon coding for the biofilm exopolysaccharide polysaccharide intercellular adhesin (PIA) were central to the regulatory impact of Rsp on virulence. Notably, the Rsp protein directly bound to the agrP2 and icaADBC promoters, resulting in strongly increased levels of the Agr-controlled toxins phenol-soluble modulins (PSMs) and alpha-toxin and reduced production of PIA. Accordingly, Rsp was essential for the development of bacteremia and skin infection, representing major types of acute S. aureus infection. Our findings give important insight into how S. aureus adapts the expression of its broad arsenal of virulence genes to promote different types of disease manifestations and identify the Rsp regulator as a potential target for strategies to control acute S. aureus infection. PMID:26712209

  19. Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.

    PubMed

    Zabaleta, Aintzane; Riezu-Boj, Jose-Ignacio; Larrea, Esther; Villanueva, Lorea; Lasarte, Juan Jose; Guruceaga, Elizabeth; Fisicaro, Paola; Ezzikouri, Sayeh; Missale, Gabriele; Ferrari, Carlo; Benjelloun, Soumaya; Prieto, Jesús; Sarobe, Pablo

    2016-05-01

    Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses, gene expression was analyzed in DC from patients during acute HCV infection. By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection. PMID:26447929

  20. Limited Immunogenicity of HIV CD8+ T-Cell Epitopes in Acute Clade C Virus Infection

    PubMed Central

    Radebe, Mopo; Nair, Kriebashnie; Chonco, Fundisiwe; Bishop, Karen; Wright, Jaclyn K.; van der Stok, Mary; Bassett, Ingrid V.; Mncube, Zenele; Altfeld, Marcus; Walker, Bruce D.

    2011-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1)–specific CD8+ responses contribute to the decline in acute peak viremia following infection. However, data on the relative immunogenicity of CD8+ T-cell epitopes during and after acute viremia are lacking. Methods. We characterized CD8+ T-cell responses in 20 acutely infected, antiretroviral-naive individuals with HIV-1 subtype C infection using the interferon-γ enzyme-linked immunosorbent spot assay. Eleven of these had not fully seroconverted at the time of analysis. Viruses from plasma were sequenced within defined cytotoxic T-lymphocyte (CTL) cell epitopes for selected subjects. Results. At approximately 28 days after estimated initial infection, CD8+ T-cell responses were directed against an average of 3 of the 410 peptides tested (range, 0–6); 2 individuals had no detectable responses at this time. At 18 weeks, the average number of peptides targeted had increased to 5 (range 0–11). Of the 56 optimal Gag CTL epitopes sequenced, 31 were wild-type in the infecting viruses, but only 11 of 31 elicited measurable CD8+ T-cell responses. Conclusions. These data demonstrate that the majority of CD8+ responses are not elicited during acute HIV infection despite the presence of the cognate epitope in the infecting strain. There is a need to define factors that influence lack of induction of effective immune responses and the parameters that dictate immunodominance in acute infection. PMID:21844303

  1. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

    PubMed Central

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L.; Frank, Daniel N.; Ma, Dongzhu; Policicchio, Benjamin B.; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S.; Trichel, Anita; Ribeiro, Ruy M.; Tracy, Russell; Wilson, Cara; Landay, Alan L.; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  2. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  3. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  4. Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia.

    PubMed

    Yui, Shunsuke; Yamaguchi, Hiroki; Imadome, Ken-Ichi; Arai, Ayako; Takahashi, Mikiko; Ohashi, Ryuji; Tamai, Hayato; Moriya, Keiichi; Nakayama, Kazutaka; Shimizu, Akira; Inokuchi, Koiti

    2016-01-01

    We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of the face. The EBV DNA copy number in whole peripheral blood was 2×10(4)/mL. Liver biopsy showed invasion of EBV-infected CD8-positive T cells. Southern blotting analysis of the whole peripheral blood showed that the T-cell receptor Cβ1 rearrangement was positive. On the basis of these results, EBV-positive T-cell LPD was diagnosed and treated with prednisolone, cyclosporine, and etoposide, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone. However, the patient died of cardiac function failure, pneumonia, and pulmonary hemorrhage, all of unidentified cause. Most cases of EBV-related LPD after hematopoietic stem cell transplantation consist of EBV-positive B-cell LPD, and, to our knowledge, de novo EBV-positive T-cell LPD subsequent to transplantation has not been previously reported. PMID:26960588

  5. Increases in Acute Hepatitis B Virus Infections - Kentucky, Tennessee, and West Virginia, 2006-2013.

    PubMed

    Harris, Aaron M; Iqbal, Kashif; Schillie, Sarah; Britton, James; Kainer, Marion A; Tressler, Stacy; Vellozzi, Claudia

    2016-01-01

    As many as 2.2 million persons in the United States are chronically infected with hepatitis B virus (HBV) (1), and approximately 15%-25% of persons with chronic HBV infection will die prematurely from cirrhosis or liver cancer (2). Since 2006, the overall U.S. incidence of acute HBV infection has remained stable; the rate in 2013 was 1.0 case per 100,000 persons (3). Hepatitis B vaccination is highly effective in preventing HBV infection and is recommended for all infants (beginning at birth), all adolescents, and adults at risk for HBV infection (e.g., persons who inject drugs, men who have sexual contact with men, persons infected with human immunodeficiency virus [HIV], and others). Hepatitis B vaccination coverage is low among adults: 2013 National Health Interview Survey data indicated that coverage with ≥3 doses of hepatitis B vaccine was 32.6% for adults aged 19-49 years (4). Injection drug use is a risk factor for both hepatitis C virus (HCV) and HBV. Among young adults in some rural U.S. communities, an increased incidence of HCV infection has been associated with a concurrent increase of injection drug use (5); and recent data indicate an increase of acute HCV infection in the Appalachian region associated with injection drug use (6). Using data from the National Notifiable Diseases Surveillance System (NNDSS) during 2006-2013, CDC assessed the incidence of acute HBV infection in three of the four Appalachian states (Kentucky, Tennessee, and West Virginia) included in the HCV infection study (6). Similar to the increase of HCV infections recently reported, an increase in incident cases of acute HBV infection in these three states has occurred among non-Hispanic whites (whites) aged 30-39 years who reported injection drug use as a common risk factor. Since 2009, cases of acute HBV infection have been reported from more non-urban than urban regions. Evidence-based services to prevent HBV infection are needed. PMID:26821369

  6. Indole-3-carbinol induces cMYC and IAP-family downmodulation and promotes apoptosis of Epstein-Barr virus (EBV)-positive but not of EBV-negative Burkitt's lymphoma cell lines.

    PubMed

    Perez-Chacon, Gema; de Los Rios, Cristobal; Zapata, Juan M

    2014-11-01

    Indole-3-carbinol (I3C) is a natural product found in broadly consumed plants of the Brassica genus, such as broccoli, cabbage, and cauliflower, which exhibits anti-tumor effects through poorly defined mechanisms. I3C can be orally administered and clinical trials have demonstrated that I3C and derivatives are safe in humans. In this study we show that I3C efficiently induces apoptosis in cell lines derived from EBV-positive Burkitt's lymphomas (virus latency I/II), while it does not have any cytotoxic activity against EBV-negative Burkitt's lymphomas and immortalized EBV-infected lymphoblastoid cell lines (virus latency III). The effect of I3C in EBV-positive Burkitt's lymphoma is very specific, since only I3C and its C6-methylated derivative, but not other 3-substituted indoles, have an effect on cell viability. I3C treatment caused apoptosis characterized by loss of mitochondria membrane potential and caspase activation. I3C alters the expression of proteins involved in the control of apoptosis and transcription regulation in EBV-positive Burkitt's lymphoma cell lines. Among those, cMYC, cIAP1/2 and XIAP downmodulation at mRNA and protein level precede apoptosis induction, thus suggesting a role in I3C cytotoxicity. We also showed that I3C and, more particularly, its condensation dimer 3,3'-diindolylmethane (DIM) prolonged survival and reduced tumor burden of mice xenotransplanted with EBV-positive Burkitt's lymphoma Daudi cells. In summary these results, together with previous reports from clinical trials indicating the lack of toxicity in humans of I3C and derivatives, support the use of these compounds as a new therapeutic approach for treating patients with endemic (EBV-positive) Burkitt's lymphoma. PMID:25180456

  7. Pathogenesis of Herpesvirus sylvilagus infection in cottontail rabbits.

    PubMed

    Hesselton, R M; Yang, W C; Medveczky, P; Sullivan, J L

    1988-12-01

    Experimental infection with Herpesvirus sylvilagus produces clinical and histopathologic changes in its natural host, the cottontail rabbit (Sylvilagus floridanus), similar to those observed in humans acutely infected with Epstein-Barr virus (EBV). Twenty-seven seronegative cottontail rabbits were infected with Herpesvirus sylvilagus and all developed antibodies within 10 days. Neutralizing antibody was detected as early as 7 days after infection. Virus was isolated from blood mononuclear cells, spleen, bone marrow, thymus, lymph nodes, kidneys, lung, and liver as early as 3 days after infection. Infected animals showed leucocytosis, monocytosis, and lymphocytosis with the appearance of atypical lymphocytes. Peripheral blood abnormalities peaked at 10-14 days after infection, and returned to normal by 28 days after infection, with the exception of atypical lymphocytosis that persisted in some animals for more than 2 years after experimental infection. More severe histopathologic changes were seen in virus-infected juvenile rabbits than adult rabbits; these changes included viral myocarditis, interstitial pneumonia, and lymphocytic myositis. Reactive hyperplasia and subsequent lymphocytic depletion of spleen and lymph nodes were reminiscent of that seen in virus-associated hemophagocytosis syndrome. Prominent lymphoid hyperplasia of many nonlymphoid organs, most notably the kidney and lungs, was observed. The development of these lymphoproliferative lesions and other lymphoid changes during H. sylvilagus infection suggest that this system may be a model to study similar lesions induced by EBV infection in humans. PMID:2849303

  8. Effect of HIV infection on time to recovery from an acute manic episode

    PubMed Central

    Nakimuli-Mpungu, E; Mutamba, B; Nshemerirwe, S; Kiwuwa, MS; Musisi, S

    2010-01-01

    Introduction Understanding factors affecting the time to recovery from acute mania is critical in the management of manic syndromes. The aim of this study was to determine the effect of HIV infection on time to recovery from acute mania. Methods We performed a retrospective study in which medical charts of individuals who were treated for acute mania were reviewed. Survival analysis with Cox regression models were used to compare time to recovery from an acute manic episode between human immunodeficiency virus (HIV)-positive individuals and HIV-negative individuals. Results Median survival time was one week for HIV-positive individuals and more than four weeks for HIV-negative individuals (χ2 = 18.4, P value = 0.000). HIV infection was the only marginally significant independent predictor of survival probability on the acute admission ward (hazards ratio 2.87, P = 0.06). Conclusion Acute mania in HIV-infected persons responds faster to psychotropic drugs compared with that in HIV-negative persons. PMID:22096397

  9. Transcriptome Analysis on Chinese Shrimp Fenneropenaeus chinensis during WSSV Acute Infection

    PubMed Central

    Sun, Zheng; Li, Fuhua; Xiang, Jianhai

    2013-01-01

    Previous studies have discovered a lot of immune-related genes responding to white spot syndrome virus (WSSV) infection in crustacean. However, little information is available in relation to underlying mechanisms of host responses during the WSSV acute infection stage in naturally infected shrimp. In this study, we employed next-generation sequencing and bioinformatic techniques to observe the transcriptome differences of the shrimp between latent infection stage and acute infection stage. A total of 64,188,426 Illumina reads, including 31,685,758 reads from the latent infection group and 32,502,668 reads from the acute infection group, were generated and assembled into 46,676 unigenes (mean length: 676 bp; range: 200–15,094 bp). Approximately 24,000 peptides were predicted and classified based on homology searches, gene ontology, clusters of orthologous groups of proteins, and biological pathway mapping. Among which, 805 differentially expressed genes were identified and categorized into 11 groups based on their possible function. Genes in the Toll and IMD pathways, the Ras-activated endocytosis process, the RNA interference pathway, anti-lipopolysaccharide factors and many other genes, were found to be activated in shrimp from latent infection stage to acute infection stage. The anti-bacterially proPO-activating cascade was firstly uncovered to be probably participated in antiviral process. These genes contain not only members playing function in host defense against WSSV, but also genes utilized by WSSV for its rapid proliferation. In addition, the transcriptome data provides detail information for identifying novel genes in absence of the genome database of shrimp. PMID:23527000

  10. Epigenetic regulation of EBV persistence and oncogenesis.

    PubMed

    Tempera, Italo; Lieberman, Paul M

    2014-06-01

    Epigenetic mechanisms play a fundamental role in generating diverse and heritable patterns of viral and cellular gene expression. Epstein-Barr virus (EBV) can adopt a variety of gene expression programs that are necessary for long-term viral persistence and latency in multiple host-cell types and conditions. The latent viral genomes assemble into chromatin structures with different histone and DNA modifications patterns that control viral gene expression. Variations in nucleosome organization and chromatin conformations can also influence gene expression by coordinating physical interactions between different regulatory elements. The viral-encoded and host-cell factors that control these epigenetic features are beginning to be understood at the genome-wide level. These epigenetic regulators can also influence viral pathogenesis by expanding tissue tropism, evading immune detection, and driving host-cell carcinogenesis. Here, we review some of the recent findings and perspectives on how the EBV epigenome plays a central role in viral latency and viral-associated carcinogenesis. PMID:24468737

  11. Epigenetic Regulation of EBV Persistence and Oncogenesis

    PubMed Central

    Tempera, Italo; Lieberman, Paul M.

    2014-01-01

    Epigenetic mechanisms play a fundamental role in generating diverse and heritable patterns of viral and cellular gene expression. Epstein-Barr Virus (EBV) can adopt a variety of gene expression programs that are necessary for long-term viral persistence and latency in multiple host-cell types and conditions. The latent viral genomes assemble into chromatin structures with different histone and DNA modifications patterns that control viral gene expression. Variations in nucleosome organization and chromatin conformations can also influence gene expression by coordinating physical interactions between different regulatory elements. The viral-encoded and host-cell factors that control these epigenetic features are beginning to be understood at the genome-wide level. These epigenetic regulators can also influence viral pathogenesis by expanding tissue tropism, evading immune detection, and driving host-cell carcinogenesis. Here, we review some of the recent findings and perspectives on how the EBV epigenome plays a central role in viral latency and viral-associated carcinogenesis. PMID:24468737

  12. Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

    PubMed

    Driver, Todd H; Terrault, Norah; Saxena, Varun

    2013-05-01

    With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease. PMID:23151989

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

    NASA Astrophysics Data System (ADS)

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

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

  14. Acute eosinophilic pneumonia as a complication of influenza A (H1N1) pulmonary infection.

    PubMed

    Larranaga, Jose Maria; Marcos, Pedro J; Pombo, Francisco; Otero-Gonzalez, Isabel

    2016-01-01

    Acute eosinophilic pneumonia (AEP) is a rare disease characterized by its acute onset and a clinical presentation simulating a bacterial pneumonia. Although it can be idiopathic, it has been described related to drugs, toxic agents and infections, mostly parasitic. We describe the case of influenza A (H1N1) severe pneumonia complicated by an acute eosinophilic pneumonia. Patient presented with respiratory failure and diffuse ground-glass opacities at chest-computed tomography. Clinical suspicion for this complication and bronchoalveolar lavage with cellular count analysis is crucial. PMID:27055842

  15. Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana

    PubMed Central

    2012-01-01

    Background Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Method Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Results Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. Conclusion The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection. PMID:22490115

  16. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection.

    PubMed

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-01-01

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells. PMID:27031961

  17. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection

    PubMed Central

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-01-01

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells. PMID:27031961

  18. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  19. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  20. Interleukin-3 protects mice from acute herpes simplex virus infection.

    PubMed Central

    Chan, W L; Ziltener, H J; Liew, F Y

    1990-01-01

    Evidence presented here from kinetic studies of interleukin-3 (IL-3) production by spleen cells from adult mice infected subcutaneously with HSV-1 and stimulated with virus antigen in vitro shows that high levels of IL-3 were produced at the onset of the animal's recovery from the disease state. Injections of anti-IL-3 antibody into HSV-1-infected mice resulted in exacerbation of the disease. Primary mouse embryonic head cells grown in the presence of murine IL-3, when infected with HSV-1, showed a 1000-fold decrease in virus titre compared with untreated control cells. This inhibiting effect was reversed by anti-IL-3 and anti-IFN-alpha, beta and gamma antibodies. These data suggest that IL-3 plays a host-protective role against HSV infection and it does so probably by inducing brain cells to produce interferons which then inhibit virus replication. PMID:2176641

  1. Acute Diffuse and Total Alopecia of the Female Scalp Associated with Borrelia-Infection

    PubMed Central

    Bhardwaj, Ekta K; Trüeb, Ralph Michel

    2015-01-01

    A case of acute diffuse and total alopecia of the female scalp associated with Borrelia-infection (acrodermatitis chronica atrophicans) is presented. Today, acute diffuse and total alopecia of the female scalp is recognized as a distinct variant of alopecia areata (AA) predominantly observed in women. Cases of AA have formerly been reported in association with infections. AA is understood to represent an organ-specific autoimmune disease of the hair follicle. It is conceivable that the antigenic stimulus provided by the infection may act as a trigger for alopecia. Vice versa, alopecia may act as a marker for detection of undiagnosed infection. Treatment of the patient with intravenous ceftriaxone led to the resolution of cutaneous borreliosis, and in addition to topical clobetasol foam to complete recovery of hair. PMID:25878446

  2. Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update

    PubMed Central

    Anderson, Deverick J.; Podgorny, Kelly; Berríos-Torres, Sandra I.; Bratzler, Dale W.; Dellinger, E. Patchen; Greene, Linda; Nyquist, Ann-Christine; Saiman, Lisa; Yokoe, Deborah S.; Maragakis, Lisa L.; Kaye, Keith S.

    2014-01-01

    PURPOSE Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their surgical site infection (SSI) prevention efforts. This document updates “Strategies to Prevent Surgical Site Infections in Acute Care Hospitals,”1 published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.2 PMID:24799638

  3. Mesangial proliferative glomerulonephritis with acute tubule interstitial nephritis leading to acute kidney injury in influenza A (H1N1) infection

    PubMed Central

    Kute, V. B.; Vanikar, A. V.; Shah, P. R.; Gumber, M. R.; Patel, H. V.; Trivedi, H. L.

    2014-01-01

    Respiratory complications and renal failure are the leading causes for morbidity and mortality due to influenza (H1N1) virus infection. There has been limited information on histopathology of H1N1 influenza-related acute kidney injury (AKI). We describe AKI with H1N1 infection in a 52-year-old female. Renal biopsy showed mesangial proliferative glomerulonephritis with acute tubule interstitial nephritis. Her condition improved rapidly with oseltamivir, fluid replacement, steroid and dialysis. Our case suggests that H1N1 infection may have a causative link to the development of mesangial proliferative glomerulonephritis with acute tubulointerstitial nephritis. PMID:24701045

  4. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    SciTech Connect

    Twu, C.-W.; Wang, W.-Y.; Liang, W.-M.; Jan, J.-S.; Jiang, R.-S.; Chao, Jeffrey; Jin, Y.-T.; Lin, J.-C. . E-mail: jclin@vghtc.gov.tw

    2007-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

  5. The association between obesity and outpatient visits for acute respiratory infections in Ontario, Canada

    PubMed Central

    Campitelli, Michael A.; Rosella, Laura C.; Kwong, Jeffrey C.

    2016-01-01

    Objectives Recent evidence suggests that obesity increases the risk of severe outcomes following respiratory infection. It is less clear whether obesity is associated with the risk of being infected with influenza or other respiratory pathogens. Therefore, we examined the association between obesity and outpatient visits for acute respiratory infections. Design We conducted a retrospective cohort study over 13 years on 104,665 individuals in Ontario, Canada who responded to population health surveys and agreed to linkage with health administrative data. Individuals aged 18–64 years who responded to a survey within 5 years prior to the start of an influenza season were included. Poisson regression, with adjustment for relevant confounders, was used to measure the association between self-reported BMI and outpatient visits coded as acute respiratory infection. We conducted numerous sensitivity analyses to assess the robustness of our findings. Results We observed higher rates of outpatient visits for ARI during influenza season periods compared with normal weight individuals for those who were overweight (BMI 25–29.9) (Rate Ratio [RR] 1.10; 95% Confidence Interval [95% CI] 1.07–1.13), obese class I (BMI 30–34.9) (RR 1.17; 95% CI 1.13–1.22), and obese class II or III (BMI ≥35) (RR 1.19; 95% CI 1.12–1.25) Associations of a similar magnitude were observed during non-influenza season periods. Obesity was a greater risk factor for acute respiratory infections managed in emergency departments than physician offices. Conclusions Obese individuals are at an increased risk of outpatient visits for acute respiratory infection during both influenza and non-influenza season periods, suggesting that the effect of obesity on the risk of respiratory infections is not limited to influenza. Interventions designed to reduce the prevalence of obesity may have the added benefit reducing the population burden of respiratory infections. PMID:23670219

  6. Infection with Mycoplasma gallisepticum buffers the effects of acute stress on innate immunity in house finches.

    PubMed

    Fratto, Melanie; Ezenwa, Vanessa O; Davis, Andrew K

    2014-01-01

    When wild animals become infected, they still must cope with the rigors of daily life, and, thus, they still can be exposed to acute stressors. The suite of physiological responses to acute stress includes modifying the innate immune system, but infections can also cause similar changes. We examined the effects of an acute stressor (capture stress) on leukocyte abundance and bacteria-killing ability (BKA) in wild birds (house finches Haemorhous mexicanus) with and without a naturally occurring infection (Mycoplasma gallisepticum) to determine whether infection alters the typical immune response to stress. Birds were captured and bled within 3 min (baseline sample) and then held in paper bags for 2 h and bled again (stress sample). From blood smears made at both time points, we obtained estimates of total white blood cell (WBC) counts and relative numbers of each cell. We also measured BKA of plasma at both time points. In uninfected birds (n = 26), total WBC count decreased by 30% over time, while in infected birds (n = 9), it decreased by 6%. Relative numbers of heterophils did not change over time in uninfected birds but increased in infected birds. Combined with a reduction in lymphocyte numbers, this led to a threefold increase in heterophil-lymphocyte values in infected birds after the stressor, compared to a twofold increase in uninfected birds. There was a nonsignificant tendency for BKA to decline with stress in uninfected birds but not in diseased birds. Collectively, these results suggest that infections can buffer the negative effects of acute stress on innate immunity. PMID:24642543

  7. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection. PMID:23381396

  8. The infant and young child during periods of acute infection

    PubMed Central

    1989-01-01

    Passive immunity, which is conferred on infants through maternal antibodies and breast milk, helps to protect them against infection during the first months of life. Later, as this immunity decreases and contact with the environment increases, the incidence of infections rises rapidly and persists at a high level during the second and third years of life. Infections and inadequate diet may be of little consequence for the well-nourished child; in underweight children, however, each episode of infection is frequently more protracted and has a considerably greater impact on health. Besides the reduced food intake and absorption, the demand for nutrients is higher during periods of infectious diseases. Infants who are exclusively breast-fed are at much lower risk from diarrhoeal diseases. In contrast, bottle-fed infants and children receiving foods other than milk, particularly in an unsanitary environment, are at much greater risk of infection from contaminated food and utensils. The period of convalescence from diarrhoeal and other disease is characterized by the return of a normal appetite and increased nutritional requirements to permit catch-up growth and the replenishment of nutritional reserves. A primary requirement is that children receive sufficient dietary energy and nutrients to enable them to achieve their growth potential. PMID:20604473

  9. Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus

    PubMed Central

    Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina

    2016-01-01

    In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. PMID:26761647

  10. Acute Babesia bovis infections: renal involvement in the hypotensive syndrome.

    PubMed

    Wright, I G; Goodger, B V

    1979-08-01

    Splenectomised calves in metabolism cages were infected with Babesia bovis. During the infection, urine samples were collected and analysed for electrolytes, proteins, kinin, and urinary kallikrein. During the later stages of the infection there were significant reductions in urinary volume, water intake, urinary kinin, kallikrein, and electrolytes. Proteinuria was detected from 3--8 days postinfection of which 15--20% was haemoglobin and most of the remainder was albumin (70--75%). Fibrin degradation products, fibrinogen-like products, and haptoglobin were not detected. Degeneration of cortical tubules was detected by histological studies. As these tubules produce urinary kallikrein it seems probable that diminished glomerular blood flow and hence glomerular filtration rate are due to decreased production of this enzyme. PMID:494708

  11. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  12. Infectious agents in human cancers: lessons in immunity and immunomodulation from gammaherpesviruses EBV and KSHV.

    PubMed

    Taylor, Graham S; Blackbourn, David J

    2011-06-28

    Members of the herpesvirus family have evolved the ability to persist in their hosts by establishing a reservoir of latently infected cells each carrying the viral genome with reduced levels of viral protein synthesis. In order to spread within and between hosts, in some cells, the quiescent virus will reactivate and enter lytic cycle replication to generate and release new infectious virus particles. To allow the efficient generation of progeny viruses, all herpesviruses have evolved a wide variety of immunomodulatory mechanisms to limit the exposure of cells undergoing lytic cycle replication to the immune system. Here we have focused on the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) that, uniquely among the eight human herpesviruses identified to date, have growth transforming potential. Most people infected with these viruses will not develop cancer, viral growth-transforming activity being kept under control by the host's antigen-specific immune responses. Nonetheless, EBV and KSHV are associated with several malignancies in which various viral proteins, either predominantly or exclusively latency-associated, are expressed; at least some of these proteins also have immunomodulatory activities. Of these malignancies, some are the result of a disrupted virus/immune balance through genetic, infectious or iatrogenic immune suppression. Others develop in people that are not overtly immune suppressed and likely modulate the immunological response. This latter aspect of immune modulation by EBV and KSHV forms the basis of this review. PMID:21470769

  13. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function. PMID:26228743

  14. [Hydrops of the gallbladder associated with Epstein-Barr virus infection].

    PubMed

    Gómez de la Torre, R; Claros González, I J; Rubio Barbón, S; Triviño López, A

    2000-01-01

    A 50-year-old male developed Hydrops of Gallbladder during the course of Epstein-Barr virus infection. The patient had a history of acute encephalitis one month prior to admission. Physical examination revealed jaundice and hepatomegaly. Liver function tests were abnormal and the white blood count was normal with 15% of atypical lymphocytes. Ultrasonography revealed a distended gall-bladder without wall thickening or cholelithiasis. The diagnoses of primary Epstein-Barr infection was made by positivity from EBV VCA IgM serological study. Two weeks later, total clinical, biochemical and ultrasonography resolution were observed. We comment this exceptionally presentation of EBV infection. The great variability of clinical pictures of Infectious Mononucleosis was emphasized. PMID:10730404

  15. Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria

    PubMed Central

    Herout, Sandra; Mandorfer, Mattias; Breitenecker, Florian; Reiberger, Thomas; Grabmeier-Pfistershammer, Katharina; Rieger, Armin; Aichelburg, Maximilian C.

    2016-01-01

    Background It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART. Methods We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis. Results Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004). Conclusions Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits. PMID:27065239

  16. Knowledge of Acute Human Immnuodeficiency Virus Infection among Gay and Bisexual Male College Students

    ERIC Educational Resources Information Center

    Grin, Benjamin; Chan, Philip A.; Operario, Don

    2013-01-01

    Objective: To examine human immunodeficiency virus (HIV)-related knowledge, attitudes, and behaviors in at-risk college men who have sex with men (MSM), focusing on knowledge about acute HIV infection (AHI). Participants and Methods: A one-time anonymous survey was administered to college students attending a lesbian, gay, bisexual, transgender,…

  17. Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening

    PubMed Central

    Green, Nella; Camacho, Martha; Gianella, Sara; Mehta, Sanjay R.; Smith, Davey M.; Little, Susan J.

    2016-01-01

    We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing. PMID:26890854

  18. Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening.

    PubMed

    Hoenigl, Martin; Green, Nella; Camacho, Martha; Gianella, Sara; Mehta, Sanjay R; Smith, Davey M; Little, Susan J

    2016-02-01

    We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing. PMID:26890854

  19. Acute infection by hepatitis E virus with a slight immunoglobulin M antibody response.

    PubMed

    Inagaki, Yuki; Oshiro, Yukio; Imanishi, Mamiko; Ishige, Kazunori; Takahashi, Masaharu; Okamoto, Hiroaki; Ohkohchi, Nobuhiro

    2015-08-01

    The anti-hepatitis E virus (HEV) immunoglobulin (Ig) M antibody response is generally regarded as a useful marker for diagnosing primary infection. However, in some cases, this antibody is not detected during the acute phase of infection. An 81-year-old man with stable membranous nephropathy who presented with asymptomatic acute liver dysfunction came to our hospital. HEV RNA of genotype 3 was detected in his serum, and he was diagnosed with acute hepatitis E. According to an enzyme-linked immunosorbent assay, high-level positivity for anti-HEV IgG and IgA antibodies was observed, but the assay was negative for IgM antibody throughout the clinical course of infection. The patient was not immunosuppressed. We further investigated the presence of IgM antibody using two other polyclonal antibodies against human IgM as secondary antibodies and another recombinant ORF2 protein of genotype 3 as an immobilized antigen. IgM was weakly detected in the serum during the acute phase only by the test with the antigen of genotype 3. Multi-genotype antigens can detect a slight IgM antibody response; however, anti-HEV IgA is more useful in diagnosing primary HEV infection, particularly in cases with a low IgM antibody response. PMID:26215116

  20. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  1. Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

    PubMed

    Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

    2011-10-01

    Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

  2. Incidence of respiratory viruses in Peruvian children with acute respiratory infections.

    PubMed

    del Valle Mendoza, Juana; Cornejo-Tapia, Angela; Weilg, Pablo; Verne, Eduardo; Nazario-Fuertes, Ronald; Ugarte, Claudia; del Valle, Luis J; Pumarola, Tomás

    2015-06-01

    Acute respiratory infections are responsible for high morbi-mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses. PMID:25784285

  3. Comparative analysis of the acute response of zebrafish Danio rerio skin to two different bacterial infections.

    PubMed

    Lü, Aijun; Hu, Xiucai; Wang, Yi; Shen, Xiaojing; Zhu, Aihua; Shen, Lulu; Ming, Qinglei; Feng, Zhaojun

    2013-12-01

    Skin is an important innate immune organ in fish; however, little is known about the skin's immune response to infectious pathogens. We conducted a comparative analysis of the acute immune response of Zebrafish Danio rerio skin against gram-positive (Staphylococcus chromogenes) and gram-negative (Citrobacter freundii) bacterial infections. Gene expression profiles induced from the two different infections were identified by microarray hybridization, with many genes demonstrating an acute immune response in the skin. Differentially expressed genes were mainly involved in response to stress and stimulus, complement activation, acute-phase response, and defense and immune response. Compared with transcription patterns of skin from the two infections, a similar innate immunity (e.g., transferrin, coagulation factor, complements, and lectins) was observed but with different acute-phase genes (e.g., ceruloplasmin, alpha-1-microglobulin, vitellogenin, and heat shock protein). These results suggest that the skin of fish plays an important role in the innate immune responses to bacterial infection. PMID:24341765

  4. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  5. Capgras-like syndrome in a patient with an acute urinary tract infection

    PubMed Central

    Salviati, Massimo; Bersani, Francesco Saverio; Macrì, Francesco; Fojanesi, Marta; Minichino, Amedeo; Gallo, Mariana; De Michele, Francesco; Chiaie, Roberto Delle; Biondi, Massimo

    2013-01-01

    Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%–40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder. PMID:23355784

  6. Human immunodeficiency virus (HIV) infection in a child presenting as acute disseminated encephalomyelitis.

    PubMed

    Tullu, Milind S; Patil, Dhananjay P; Muranjan, Mamta N; Kher, Archana S; Lahiri, Keya R

    2011-01-01

    Acute disseminated encephalomyelitis is an extremely rare occurrence in human immunodeficiency virus (HIV) infection. We describe an 8-year-old male child who presented with weakness of both lower limbs for 10 days and focal convulsions for 2 days. The child had left, upper motor neuron facial palsy, lower limb hypotonia, and exaggerated deep tendon reflexes. Enzyme-linked immunosorbent assay antibodies for HIV tested positive and the CD4 count was 109 cells/µL. The magnetic resonance imaging (MRI, brain) revealed extensive confluent hyperintensities (on T2-weighted images) in left parietal, right temporal, and right occipital regions of the white matter, and similar signals were seen in right lentiform nucleus and right posterior thalami, suggesting acute disseminated encephalomyelitis. There was transient improvement with intravenous methyl prednisolone. The patient succumbed to the illness. Perinatally transmitted pediatric HIV infection presenting with acute disseminated encephalomyelitis has not yet been reported in the medical literature. PMID:20656677

  7. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.

    PubMed

    Buenz, Eric J; Sauer, Brian M; Lafrance-Corey, Reghann G; Deb, Chandra; Denic, Aleksandar; German, Christopher L; Howe, Charles L

    2009-08-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  8. CHALLENGE WITH BOVINE VIRAL DIARRHEA VIRUS BY EXPOSURE TO PERSISTENTLY INFECTED CALVES: PROTECTION BY VACCINATION AND NEGATIVE RESULTS OF ANTIGEN TESTING IN NONVACCINATED ACUTELY INFECTED CALVES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) represent an important source of infection for susceptible cattle. We evaluated vaccine efficacy using calves PI with noncytopathic BVDV2a for the challenge and compared tests to detect BVDV in acutely or transiently infected ...

  9. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    SciTech Connect

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  10. Magnetic Resonance Imaging of Acute Head and Neck Infections.

    PubMed

    Thayil, Neil; Chapman, Margaret N; Saito, Naoko; Fujita, Akifumi; Sakai, Osamu

    2016-05-01

    This article discusses the use of MR imaging in various acute infectious diseases of the head and neck, with particular emphasis on situations where MR imaging provides additional information that can significantly impact treatment decisions and outcomes. MR imaging findings of various disease processes are discussed, based on the head and neck compartments from which they originate. Specifically, infectious entities of the orbit, paranasal sinuses, pharynx, oral cavity (including periodontal disease), salivary glands, temporal bone, and lymph nodes are described in detail. PMID:27150323

  11. Prognostic Significance of EBV Latent Membrane Protein 1 Expression in Lymphomas: Evidence from 15 Studies

    PubMed Central

    Mao, Yuan; Lu, Mei Ping; Lin, Hong; Zhang, Da Wei; Liu, Ying; Li, Qing Dong; Lv, Zhi Gang; Xu, Jia Ren; Chen, Ren Jie; Zhu, Jin

    2013-01-01

    Background Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma. Methods The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival. Results Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92–1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR  = 1.84, 95% CI: 1.02–3.34), but not with survival of patients with Hodgkin disease (HD) (HR  =  1.03, 95% CI: 0.74–1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value. Conclusions This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression. PMID:23613723

  12. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  13. Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

    PubMed

    Kamaladasa, A; Wickramasinghe, N; Adikari, T N; Gomes, L; Shyamali, N L A; Salio, M; Cerundolo, V; Ogg, G S; Malavige, G Neelika

    2016-08-01

    Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. PMID:26874822

  14. Association of Interleukin-8 and Neutrophils with Nasal Symptom Severity During Acute Respiratory Infection

    PubMed Central

    Henriquez, Kelsey M.; Hayney, Mary S.; Xie, Yaoguo; Zhang, Zhengjun; Barrett, Bruce

    2015-01-01

    Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (rs = 0.082, P = 0.022; rs = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <0.00001; r = 0.18, P = <0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = −0.02, P = <0.0001; r = −0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. PMID:25132248

  15. New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media

    PubMed Central

    Leino, Tuija; Kilpi, Terhi

    2016-01-01

    For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2–24 months at scheduled visits and at visits during respiratory infection in 1994–97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media. PMID:27257789

  16. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

    PubMed Central

    Gånheim, C; Höglund, J; Waller, K Persson

    2004-01-01

    Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP) haptoglobin, serum amyloid A (SAA) and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I) 250 D. viviparus infective third stage larvae (L3) once daily for 2 consecutive days, II) 100 D. viviparus L3 once daily for 5 consecutive days, and III) 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals. PMID:15535088

  17. Hepatitis C and leptospirosis: simultaneous acute infections or recurrence of occult hepatitis C.

    PubMed

    Ferraz, Rita Veiga; Pereira, Nuno Rocha; Carvalho, Cláudia; Sarmento, António

    2015-01-01

    People who inject drugs are vulnerable to several infections. To the best of our knowledge, this is the first case report of a simultaneous diagnosis of leptospirosis and acute infection or recurrence of occult hepatitis C in an HIV-infected drug user. We report a case of a 47-year-old Caucasian man with HIV infection, on antiretroviral therapy, and with a history of hepatitis C (positive anti-hepatitis C virus (HCV) and HCV RNA persistently negative) who was admitted with febrile acute hepatitis. He was a former injecting drug user, on opioid substitution therapy, who relapsed to injection drug use 3 weeks prior to admission. Work up revealed positive HCV RNA and Leptospira DNA in his urine. Four weeks later he had an undetectable HCV load, and also at 6 months of follow-up. This case highlights the presence of two concomitant infectious aetiologies of acute hepatitis in an HIV-infected drug user. PMID:26135490

  18. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

    PubMed

    Phuong, Hoang Lan; Nga, Tran T T; van Doornum, Gerard J; Groen, Jan; Binh, Tran Q; Giao, Phan T; Hung, Le Q; Nams, Nguyen V; Kager, P A; de Vries, Peter J

    2010-09-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%. PMID:21073032

  19. Sexual dimorphism in lung function responses to acute influenza A infection

    PubMed Central

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

  20. A cluster of acute hepatitis E infection in United Nations Bangladeshi peacekeepers in Haiti.

    PubMed

    Drabick, J J; Gambel, J M; Gouvea, V S; Caudill, J D; Sun, W; Hoke, C H; Innis, B L

    1997-10-01

    In the fall of 1995, within a month of deployment to Haiti for peacekeeping duty, four Bangladeshi soldiers developed acute icteric hepatitis in rapid succession. Hepatitis E virus (HEV) was found to be the etiology by demonstrating HEV genomic sequences in serum samples by the polymerase chain reaction (PCR) and serologically by the detection of elevated IgM titers to HEV. No case had serologic evidence of acute hepatitis A or C infection. The soldiers had probably acquired their infection while living in a cantonment area outside Dhaka, Bangladesh for one month prior to deployment. Cloning and sequencing of amplified PCR products demonstrated a single strain suggestive of a common source of infection. Furthermore, high genomic identity with Asian strains of HEV and dissimilarity with the Mexican strain was demonstrated, verifying that the strain had indeed been imported. Human waste management from the Bangladesh camp in Haiti was strictly controlled and no secondary cases were observed. A convenience sample of 105 (12%) soldiers from the Bangladesh battalion (850 men) revealed anicteric or asymptomatic HEV infection in seven (7%) of 105. This report contains the first demonstration of acute hepatitis E in natives of Bangladesh and demonstrates the power of the PCR in the rapid diagnosis and epidemiologic analysis of HEV infection. More importantly, this cluster demonstrates the importation of an important infectious disease by multinational peacekeepers to a potentially susceptible host country. PMID:9347962

  1. Is accounting for acute care beds enough? A proposal for measuring infection prevention personnel resources.

    PubMed

    Gase, Kathleen A; Babcock, Hilary M

    2015-02-01

    There is still little known about how infection prevention (IP) staffing affects patient outcomes across the country. Current evaluations mainly focus on the ratio of IP resources to acute care beds (ACBs) and have not strongly correlated with patient outcomes. The scope of IP and the role of the infection preventionist in health care have expanded and changed dramatically since the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) recommended a 1 IP resource to 250 ACB ration in the 1980s. Without a universally accepted model for accounting for additional IP responsibilities, it is difficult to truly assess IP staffing needs. A previously suggested alternative staffing model was applied to acute care hospitals in our organization to determine its utility. PMID:25480447

  2. Acute ulcerative proctocolitis associated with primary cytomegalovirus infection.

    PubMed

    Diepersloot, R J; Kroes, A C; Visser, W; Jiwa, N M; Rothbarth, P H

    1990-08-01

    The case is reported of a 39-year-old pregnant woman who presented with fever, abdominal complaints, and diarrhea. Laboratory investigation revealed mononucleosis in the peripheral blood. All microbiological studies were negative, with the exception of finding cytomegalovirus (CMV). Seroconversion was documented; the virus was cultured from urine and subsequently was demonstrated to be present in the inflamed mucosa of the rectum and distal sigmoid, which was found at sigmoidoscopy. This woman was delivered of a neonate with congenital CMV infection but without apparent malformations. The patient experienced recurrences of the bowel disease, in the first of which CMV could still be cultured from a biopsy specimen. In the follow-up period, an otherwise aspecific chronic inflammatory bowel disease remained present. No immunological abnormalities were found, and antibodies to human immunodeficiency virus were negative. This case demonstrates that inflammatory bowel disease can develop as a result of primary infection with CMV. PMID:2166491

  3. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  4. Knowledge and Awareness of Acute Human Immunodeficiency Virus Infection Among Mobile App-Using Men Who Have Sex With Men: A Missed Public Health Opportunity

    PubMed Central

    Siegler, Aaron J.; Sanchez, Travis; Sineath, R. Craig; Grey, Jeremy; Kahle, Erin; Sullivan, Patrick S.

    2015-01-01

    In a national online survey, we assessed awareness and knowledge of acute human immunodeficiency virus (HIV) infection manifestation among 1748 men who have sex with men (MSM). Only 39% of respondents were aware that acute HIV infection may be accompanied by symptoms. Education and increased access to acute HIV testing may facilitate MSM to appropriately seek acute HIV testing. PMID:26034766

  5. Increased EBV Shedding in Astronaut Saliva During Spaceflight

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Stowe, R. P.; Phillips, T.; Lugg, D. J.; Mehta, S. K.

    2003-01-01

    Shedding of Epstein-Barr virus (EBV) by astronauts before, during, and after space shuttle missions was quantified. Of 1398 saliva specimens from 32 astronauts, 314 (23%) were positive for EBV DNA by PCR analysis. Of the saliva specimens collected before flight, 29% were positive for EBV DNA and of those collected during or after flight, 16% were EBV-positive. The number of EBV DNA copies from samples taken during the flight was 417+/-31, significantly higher (P < 0.05) than the number of copies from the preflight (40+/-1.7) and postflight (44+/-5) phases. Eighteen control subjects shed EBV DNA with a frequency of 3.7% and a copy number of 40+/-2 per ml saliva. Ten days before flight and on landing day, antibody titers to EBV viral capsid antigen (VCA) were significantly (P < 0.05) higher than baseline levels. On landing day, urinary level of cortiso1 and catecholamines, and plasma levels of substance P and other neuropeptides, were increased over their preflight value. Results suggested that stress associated with spaceflight decreases cellular immunity and thereby leads to increased viral reactivation.

  6. EBV DNA polymerase inhibition of tannins from Eugenia uniflora.

    PubMed

    Lee, M H; Chiou, J F; Yen, K Y; Yang, L L

    2000-06-30

    Nasopharyngeal carcinoma (NPC) is one of the high population malignant tumors among Chinese in southern China and southeast Asia. Epstein-Barr virus (EBV) is a human B lymphotropic herpes virus which is known to be closely associated with NPC. EBV DNA polymerase is a key enzyme during EBV replication and is measured by its radioactivity. The addition of phorbol 12-myristate 13-acetate to Raji cell cultures led to a large increase in EBV DNA polymerase, which was purified by sequential DEAE-cellulose, phosphocellulose and DNA-cellulose column chromatography. Four tannins were isolated from the active fractions of Eugenia uniflora L., which were tested for the inhibition of EBV DNA polymerase. The results showed the 50% inhibitory concentration (IC(50)) values of gallocatechin, oenothein B, eugeniflorins D(1) and D(2) were 26.5 62.3, 3.0 and 3.5 microM, respectively. Furthermore, when compared with the positive control (phosphonoacetic acid), an inhibitor of EBV replication, the IC(50) value was 16.4 microM. In view of the results, eugeniflorins D(1) and D(2) are the potency principles in the inhibition of EBV DNA polymerase from E. uniflora. PMID:10806300

  7. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed. PMID:27084183

  8. Acute compartment syndrome of the forearm secondary to infection within the space of Parona.

    PubMed

    Jamil, Wiqqas; Khan, Irfan; Robinson, Paul; Thalava, Ramesh

    2011-09-01

    The deep midpalmar space of the hand communicates with the space of Parona in the forearm. Infection of these deep spaces can be difficult to diagnose. This article presents the first reported case of acute compartment syndrome of the forearm secondary to infection within the space of Parona. This article discusses the anatomy of the space of Parona, highlighting its communicating spaces and the importance of recognizing a deep-space infection of the hand as a possible cause of compartment syndrome of the forearm. This article also suggests a method of clinical examination to aid in the diagnosis of infection within the space of Parona to allow more specific planning of surgical intervention through early decompressive surgery, with surgical exploration to exclude and drain infection when no other clear cause for the rise in pressure within the osteofascial compartment is apparent. PMID:21902163

  9. Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.

    PubMed

    Cote, P J; Toshkov, I; Bellezza, C; Ascenzi, M; Roneker, C; Ann Graham, L; Baldwin, B H; Gaye, K; Nakamura, I; Korba, B E; Tennant, B C; Gerin, J L

    2000-10-01

    Acute hepatitis B virus (HBV) infections either resolve or progress to chronicity. Identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. Neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver were obtained from infected animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined outcome of infection. As of 1 year postinfection, half of the surgically treated infected woodchucks had developed self-limited infections, while the other half developed chronic infections. The self-limited outcome was characterized by decreased viral load in acute-phase liver and plasma and a generally robust acute hepatic inflammatory response. Comparisons at the same early time points revealed that the chronic outcome was characterized by increasing initial viral load in liver and plasma, and a detectable, but diminished, acute hepatic inflammation. These cotemporal comparisons indicate that there is an early host-response deviation during the acute phase of a developing chronic infection. Continued analysis of the tissues banked from this study will facilitate further temporal characterization of acute-phase mechanisms that determine resolution versus chronicity in WHV infection. Understanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection. PMID:11003627

  10. Estimating the impact of vaccination in acute SHIV-SIV infection

    SciTech Connect

    Ribeiro, Ruy

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  11. Virus-Specific CD8(+) T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected With CMV and/or EBV.

    PubMed

    Heutinck, K M; Yong, S L; Tonneijck, L; van den Heuvel, H; van der Weerd, N C; van der Pant, K A M I; Bemelman, F J; Claas, F H J; Ten Berge, I J M

    2016-05-01

    T cells play a dual role in transplantation: They mediate transplant rejection and are crucial for virus control. Memory T cells generated in response to pathogens can cross-react to alloantigen, a phenomenon called heterologous immunity. Virus-specific CD8(+) T cells cross-reacting to donor-alloantigen might affect alloimmune responses and hamper tolerance induction following transplantation. Here, we longitudinally studied these cross-reactive cells in peripheral blood of 25 kidney transplant recipients with a cytomegalovirus and/or Epstein-Barr virus infection. Cross-reactive T cells were identified by flow cytometry as virus-specific T cells that proliferate in response to donor cells in a mixed-lymphocyte reaction. In 13 of 25 patients, we found cross-reactivity to donor cells for at least 1 viral epitope before (n = 7) and/or after transplantation (n = 8). Cross-reactive T cells were transiently present in the circulation, and their precursor frequency did not increase following transplantation or viral infection. Cross-reactive T cells expressed interferon-γ and CD107a in response to both alloantigen and viral peptide and resembled virus-specific T cells in phenotype and function. Their presence was not associated with impaired renal function, proteinuria, or rejection. In conclusion, virus-specific T cells that cross-react to donor-alloantigen are transiently detectable in the circulation of kidney transplant recipients. PMID:26603974

  12. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

    PubMed

    Kløverpris, Henrik N; Kazer, Samuel W; Mjösberg, Jenny; Mabuka, Jenniffer M; Wellmann, Amanda; Ndhlovu, Zaza; Yadon, Marisa C; Nhamoyebonde, Shepherd; Muenchhoff, Maximilian; Simoni, Yannick; Andersson, Frank; Kuhn, Warren; Garrett, Nigel; Burgers, Wendy A; Kamya, Philomena; Pretorius, Karyn; Dong, Krista; Moodley, Amber; Newell, Evan W; Kasprowicz, Victoria; Abdool Karim, Salim S; Goulder, Philip; Shalek, Alex K; Walker, Bruce D; Ndung'u, Thumbi; Leslie, Alasdair

    2016-02-16

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction. PMID:26850658

  13. An unusual case of infective endocarditis presenting as acute myocardial infarction.

    PubMed

    Chen, Zhong; Ng, Francesca; Nageh, Thuraia

    2007-06-01

    A 39-year-old Zimbabwean man presented with a 1 week history of fever, general malaise and acute-onset chest pain. He had a urethral stricture, which had been managed with an indwelling supra-pubic catheter. The electrocardiography on admission showed inferior ST-T segments elevation. His chest pain and electrocardiography changes resolved subsequent to thrombolysis, and he remained haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a flail anterior mitral valve leaflet with an independently oscillating mobile vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of enterococci infective endocarditis with concomitant acute myocardial infarction due to possible septic emboli was made. Despite the successful outcome from thrombolysis in the setting of acute myocardial infarction with infective endocarditis, the case highlights the current lack of definitive data on the optimal acute management of such an unusual clinical scenario. Although there is serious concern that thrombolytic treatment for myocardial infarction in the setting of infective endocarditis may be associated with higher risk of cerebral haemorrhage, there is little documented evidence supporting the safety of primary percutaneous coronary intervention with these patients. PMID:17513553

  14. Enhanced resistance to acute infection with Trypanosoma cruzi in mice treated with an interferon inducer.

    PubMed Central

    James, S L; Kipnis, T L; Sher, A; Hoff, R

    1982-01-01

    For an exploration of the effects of interferon-inducible resistance mechanisms in acute American trypanosomiasis, the synthetic interferon inducer tilerone hydrochloride was administered to mice of the C57BL/6J strain, which is highly resistant to Trypanosoma cruzi, 18 to 24 h before infection with a potentially lethal dose of bloodstream trypomastigotes. Although all of the control mice died within 30 days of the acute infection, approximately 50% of the tilerone-treated animals were able to survive indefinitely (P less than 0.05). The tilerone-treated mice demonstrated significant levels of serum interferon and splenic natural killer cells at the time of infection. Macrophages isolated from the peritoneal cavities of tilerone-treated C57BL/6J mice appeared to kill significant numbers of trypanosomes during 2 to 3 days of in vitro culture, indicating that activated macrophages may contribute to the enhanced resistance to T. cruzi infection in these mice. Beige mice treated with tilerone did not survive T. cruzi infection as well as tilerone-treated heterozygotes did, suggesting a role for natural killer cells in interferon-induced resistance. These results suggest that interferon or effector mechanisms enhanced by interferon induction can play a significant role in influencing resistance to T. cruzi infection. PMID:6173326

  15. Serological diagnosis and follow-up of asymptomatic and acute Q fever infections.

    PubMed

    Wagner-Wiening, Christiane; Brockmann, Stefan; Kimmig, Peter

    2006-05-01

    During an outbreak of Q fever at a farmer's market in Soest (North Rhine-Westphalia, Germany) in 2003, we examined 263 serum samples of presumably infected persons for Q fever antibodies. One hundred and seventy-one of these patients were tested positive for acute Q fever infection. Furthermore, 29 persons of certain risk groups like pregnant women (n=11) or patients with valvular heart disease (n=18) were examined. Among these, in four pregnant women and two heart patients an acute but asymptomatic infection could be diagnosed. With 30 patients we performed a serological follow-up for 8-60 weeks. In our study, phase 2 (PH2)-IgM antibodies as a marker for acute infection were present in all 30 patients 3-4 weeks after onset of clinical signs and disappeared 3-4 months later. Six weeks to three months after clinical manifestation, all patients developed PH1-IgG antibodies in low levels with no clinical signs of chronic Q fever. Three patients, including one pregnant woman showed high-level titres and were treated for chronic Q fever. Eleven patients with low PH1-IgG antibodies and all three patients with high titres developed IgA antibodies from 10 weeks after clinical manifestation; therefore PH1-IgA cannot be used as the only serological marker for chronic Q fever. Chronic infections were indicated only by a continuous increase of PH1 antibodies and a high persistence of PH2-IgG. We therefore conclude that the exclusion of chronic Q fever infection by a single serological examination cannot be done. At least three consecutive tests should be performed, that is 3, 6, and 9 months after initial Q fever infection. PMID:16524773

  16. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect

    Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

    1985-10-01

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

  17. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.

    PubMed

    Du, Victor Y; Bansal, Anju; Carlson, Jonathan; Salazar-Gonzalez, Jesus F; Salazar, Maria G; Ladell, Kristin; Gras, Stephanie; Josephs, Tracy M; Heath, Sonya L; Price, David A; Rossjohn, Jamie; Hunter, Eric; Goepfert, Paul A

    2016-04-15

    Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen. PMID:26983786

  18. Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Dore, Gregory J.; Grebely, Jason

    2015-01-01

    Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex

  19. Middle ear squamous papilloma: A report of four cases analyzed by HPV and EBV in situ hybridization

    PubMed Central

    ZHOU, HAN; CHEN, ZHIBIN; ZHANG, WEIMING; XING, GUANGQIAN

    2014-01-01

    Squamous papilloma involving the middle ear as a primary lesion is an extremely rare occurrence. The aims of the present study were to investigate the presence of human papilloma virus (HPV) and Epstein-Barr virus (EBV) infections in primary middle ear squamous papilloma and to describe the clinical and pathological features of the disease along with therapeutic strategies. A retrospective review was conducted of four patients with clinical and pathological diagnoses of middle ear squamous papilloma. In situ hybridization (ISH) for a wide range of HPV DNA subtypes and EBV-encoded RNA was performed in the tissue samples obtained from these patients. Only two cases of primary squamous papilloma in the middle ear have been previously reported in the English literature. These papillomas developed in males of ~60-years of age and otorrhea was the most frequent complaint. Premalignant changes were observed in two of the present cases and ISH of HPV and EBV was negative in all four cases. The results of the present study indicated that chronic inflammatory stimulation, not HPV and EBV infection, is involved in the occurrence of middle ear squamous papilloma and its malignant transformation. Radical surgery and long-term postoperative follow-up are recommended due to its malignant and recurrent potential. Further genetic investigations with additional new cases are required to clarify the pathogenesis of squamous papilloma involving the middle ear. PMID:24348817

  20. A Pediatric Case of Acute Generalized Pustular Eruption without Streptococcal Infection

    PubMed Central

    Tabata, Nobuko; Yoshizawa, Hideka

    2016-01-01

    Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226

  1. The Acute Respiratory Infection Quality Dashboard: a performance measurement reporting tool in an electronic health record.

    PubMed

    Linder, Jeffrey A; Jung, Eunice; Housman, Dan; Eskin, Michael S; Schnipper, Jeffrey L; Middleton, Blackford; Einbinder, Jonathan S

    2007-01-01

    Quality reporting tools, integrated with electronic health records, can help clinicians understand performance, manage populations, and improve quality. The Acute Respiratory Infection Quality Dashboard (ARI QD) for LMR users is a secure web report for performance measurement of an acute condition delivered through a central data warehouse and custom-built reporting tool. Pilot evaluation of the ARI QD indicates that clinicians prefer a quality report that combines not only structured data regarding diagnosis and antibiotic prescribing rates entered into EHRs but one that also shows billing data. The ARI QD has the potential to reduce inappropriate antibiotic prescribing for ARIs. PMID:18694133

  2. Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children

    PubMed Central

    Moesker, Fleur M.; van Kampen, Jeroen J. A.; van Rossum, Annemarie M. C.; de Hoog, Matthijs; Koopmans, Marion P. G.; Osterhaus, Albert D. M. E.; Fraaij, Pieter L. A.

    2016-01-01

    Background Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Conclusion Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified. PMID:26964038

  3. EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management

    PubMed Central

    Ok, Chi Young; Li, Ling; Young, Ken H

    2015-01-01

    Epstein–Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders. PMID:25613729

  4. EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature.

    PubMed

    Nejati, Ahmad; Shoja, Zabihollah; Shahmahmoodi, Shohreh; Tafakhori, Abbas; Mollaei-Kandelous, Yaghoub; Rezaei, Farhad; Hamid, Kabir Magaji; Mirshafiey, Abbas; Doosti, Rozita; Sahraian, Mohammad Ali; Mahmoudi, Mahmood; Shokri, Fazel; Emery, Vince; Marashi, Sayed Mahdi

    2016-04-01

    Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88.6 % in the healthy group (p = 0.005). EBV DNA load was significantly higher in MS patients than healthy subjects (p < 0.0001). Using a panel of biomarkers, we found a distinct transcriptional signature in MS patients compared to the healthy group with mRNA levels of CD73, IL-6, IL-23, IFN-γ, TNF-α, IL-15, IL-28, and IL-17 significantly elevated in MS patients (p < 0.0001). In contrast, the mRNA levels for TGF-β, IDO, S1PR1, IL-10, and CCL-3 were significantly lower in MS patients compared to healthy controls (p < 0.0001). No significant differences were found with the mRNA levels of IL-13, CCL-5, and FOXP3. Interestingly, in MS patients we found an inverse correlation between vitamin D concentration and EBV load, but not EBNA-1 IgG antibody levels. Our data highlight biomarker correlates in MS patients together with a complex interplay between EBV replication and vitamin D levels. PMID:26365612

  5. Rapid Homogeneous Immunoassay Based on Time-Resolved Förster Resonance Energy Transfer for Serodiagnosis of Acute Hantavirus Infection

    PubMed Central

    Hepojoki, Satu; Hedman, Klaus; Vapalahti, Olli; Vaheri, Antti

    2014-01-01

    We recently introduced a homogeneous immunoassay based on time-resolved Förster resonance energy transfer (TR-FRET) elicited by fluorophore-labeled antigen and fluorophore-labeled protein L, bound by an immunoglobulin. As the first clinical application, we employ this approach (LFRET) in serodiagnosis of Puumala hantavirus (PUUV) infection. A reference panel containing serum from individuals with acute (n = 21) or past (n = 17) PUUV infection and from PUUV-seronegative individuals (n = 20) was used to define the parameters. The clinical assay performance was evaluated with a prospectively collected serum panel (panel 2; n = 153). Based on the results for panel 1, the threshold for positivity was set at a signal level that was 3-fold over background, while those with a signal <3-fold over the background level were considered PUUV seronegative. With panel 1, 20/21 acute- and 7/10 past-infection samples induced positive signals, compared to 0/20 seronegatives. With panel 2, a positive signal was obtained in 39/40 acute- and 4/10 past-infection samples, as opposed to 7/103 seronegatives. However, after IgG depletion, 58/61 acute-infection samples were LFRET positive, while all past-infection and seronegative samples were negative, corresponding to 100% specificity and 95% sensitivity in detection of acute PUUV infection. We demonstrate that the novel immunoassay is a promising tool for rapid serodiagnosis of acute Puumala virus infection. PMID:25520445

  6. EBV-encoded RNA via TLR3 induces inflammation in nasopharyngeal carcinoma.

    PubMed

    Li, Zhi; Duan, Yumei; Cheng, Shiyue; Chen, Yan; Hu, Yanxin; Zhang, Lu; He, Jiang; Liao, Qiong; Yang, Lifang; Sun, Lun-Quan

    2015-09-15

    Pathogen-induced inflammation has been one of the intensive research areas in carcinogenesis. EBV encoded RNAs (EBERs) have been suggested to play roles in anti-apoptosis and growth-promotion in lymphoid and immune disorders. However, pathological roles of EBERs in solid tumors of epithelia origin remain to be elucidated. Given their characteristic dsRNA structures, recent studies provided evidences for the activation of some pattern recognition receptors (PRR) by EBERs, which is fundamental in the process of pathogenesis. Here, we show that EBERs induce inflammatory response in nasopharyngeal carcinoma (NPC) cells through Toll-like receptor 3 (TLR3), mainly featured by high level of TNFα production. Interestingly, EBERs and EBV latent membrane protein 1 (LMP1) form a positive regulatory loop with NF-κB as a key node that amplifies the inflammatory signals in EBV infected epithelial cells. We demonstrate in vivo that EBERs can interact with TLR3 and induce tumor cells to produce cytokines in B16 synergetic tumor and human NPC xenograft models, in which macrophages are recruited and activated, leading to a favorable microenvironment for solid tumor growth. Lastly, we verify a positive association between EBER and TNFα levels in NPC clinical samples and the combination of EBER and TNFα expressions provides a predictor of poor survival of NPC patients. In conclusion, EBERs play a pivotal role in inflammation-to-oncogenesis transition in NPC development. PMID:26172457

  7. Bone marrow is a major site of long-term antibody production after acute viral infection.

    PubMed Central

    Slifka, M K; Matloubian, M; Ahmed, R

    1995-01-01

    Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase

  8. Natural History of Primary Epstein-Barr Virus Infection in Children of Mothers Infected with Human Immunodeficiency Virus Type 1

    PubMed Central

    Jenson, Hal; McIntosh, Kenneth; Pitt, Jane; Husak, Scott; Tan, Ming; Bryson, Yvonne; Easley, Kirk

    2015-01-01

    The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1–infected mothers was studied in a prospective, multicenter, cohort study. HIV-1–infected children had a cumulative EBV infection rate similar to HIV-1–uninfected children at age 3 years (77.8% vs. 84.9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28.2%; P < .001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1–uninfected children 3 years after seroconversion. HIV-1–infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P = .01). HIV-1–infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1–infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding. PMID:10228060

  9. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy

    PubMed Central

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-01-01

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research. PMID:27468190

  10. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy.

    PubMed

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-07-14

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research. PMID:27468190

  11. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus▿

    PubMed Central

    McCray, Paul B.; Pewe, Lecia; Wohlford-Lenane, Christine; Hickey, Melissa; Manzel, Lori; Shi, Lei; Netland, Jason; Jia, Hong Peng; Halabi, Carmen; Sigmund, Curt D.; Meyerholz, David K.; Kirby, Patricia; Look, Dwight C.; Perlman, Stanley

    2007-01-01

    The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies. PMID:17079315

  12. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic

  13. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe

  14. Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

    PubMed

    Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

    2016-04-01

    Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. PMID:26515793

  15. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  16. Analysis of Epstein-Barr virus (EBV) nuclear antigen 1 subtypes in EBV-associated lymphomas from Brazil and the United Kingdom.

    PubMed

    MacKenzie, J; Gray, D; Pinto-Paes, R; Barrezueta, L F; Armstrong, A A; Alexander, F A; McGeoch, D J; Jarrett, R F

    1999-10-01

    EBNA-1 is the only viral protein consistently expressed in all cells latently infected by Epstein-Barr virus (EBV). There is a high frequency of sequence variation within functionally important domains of EBNA-1, with five subtypes identified. Individuals may be infected with multiple EBV strains (classified according to EBNA-1 subtype), but Burkitt's lymphoma (BL) tumours carry a single subtype and exhibit some subtype preference. Subtype variation has also been related to geographical location. In the present study EBNA-1 polymorphisms were examined in a series of haematological malignancies from two distinct geographical regions, Brazil and the United Kingdom. Nucleotide sequence analysis of the carboxy-terminal region of EBNA-1 in 34 cases revealed six distinct sequences, some of which are novel. A new subtype, named V-Ala, was identified. EBNA-1 subtype in tumours differed markedly according to geographical location. In contrast to previous studies, we found evidence of EBNA-1 sequence variation within individual BL tumour samples. PMID:10573169

  17. Anemia and mechanism of erythrocyte destruction in ducks with acute Leucocytozoon infections

    USGS Publications Warehouse

    Kocan, R.M.

    1968-01-01

    In the anemia which accompanies infection by Leucocytozoon simondi in Pekin ducks there was a far greater loss of erythrocytes than could be accounted for as a result of direct physical rupture by the parasite. Erythrocyte loss began at the same time the 1st parasites appeared in the blood and was severest just prior to maximum parasitemia. Blood replacement and parasite loss occurred simultaneously. Examination of the spleen and bone marrow revealed that erythrophagocytosis was not the cause of anemia as reported for infections of Plasmodium, Babesia and Anaplasma. An anti-erythrocyte (A-E) factor was found in the serum of acutely infected ducks which agglutinated and hemolyzed normal untreated duck erythrocytes as well as infected cells. This A-E factor appeared when the 1st red cell loss was detected and reached its maximum titer just prior to the greatest red cell loss. Titers of the A-E factor were determined using normal uninfected erythrocytes at temperatures between 4 and 42 C. Cells agglutinated below 25 C and hemolyzed at 37 and 42 C. These results indicated that the A-E factor could be responsible for loss of cells other than those which were infected and could thus produce an excess loss of red cells. Attempts to implicate the A-E factor as an autoantibody were all negative. The A-E factor was present in the gamma fraction of acute serum but no anamnestic response could be detected when recovered ducks were reinfected. Anemia was never as severe in reinfections as in primary infections. The A-E factor also never reached as high a titer and was removed from the circulation very rapidly in reinfected ducks. It is concluded that red cell loss in ducks with acute Leucocytozoon disease results from intravascular hemolysis rather than erythrophagocytosis. The A-E factor responsible for hemolysis is more likely a parasite product rather than autoantibody.

  18. Measurement of CD8+ and CD4+ T Cell Frequencies Specific for EBV LMP1 and LMP2a Using mRNA-Transfected DCs.

    PubMed

    Sohn, Dae-Hee; Sohn, Hyun-Jung; Lee, Hyun-Joo; Lee, Seon-Duk; Kim, Sueon; Hyun, Seung-Joo; Cho, Hyun-Il; Cho, Seok-Goo; Lee, Suk-Kyeong; Kim, Tai-Gyu

    2015-01-01

    An EBV-specific cellular immune response is associated with the control of EBV-associated malignancies and lymphoproliferative diseases, some of which have been successfully treated by adoptive T cell therapy. Therefore, many methods have been used to measure EBV-specific cellular immune responses. Previous studies have mainly used autologous EBV-transformed B-lymphoblastoid cell lines (B-LCLs), recombinant viral vectors transfected or peptide pulsed dendritic cells (DCs) as stimulators of CD8(+) and CD4(+) T lymphocytes. In the present study, we used an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay by using isolated CD8(+) and CD4(+) T cells stimulated with mRNA-transfected DCs. The frequency of latent membrane protein 1 (LMP1)-specific IFN-γ producing CD4(+) T cells was significantly higher than that of LMP2a. The frequency of IFN-γ producing CD4(+) T cells was significantly correlated with that of CD8(+) T cells in LMP1-specific immune responses (r = 0.7187, Pc < 0.0001). To determine whether there were changes in LMP1- or LMP2a-specific immune responses, subsequent peripheral blood mononuclear cells (PBMCs) samples were analyzed. Significant changes were observed in 5 of the 10 donors examined, and CD4(+) T cell responses showed more significant changes than CD8(+) T cell responses. CD8(+) and CD4(+) T cells from EBV-seropositive donors secreted only the Th1 cytokines IFN-γ, TNF-α, and IL-2, while Th2 (IL-4) and Th17 (IL-17a) cytokines were not detected. CD4(+) T cells secreted significantly higher cytokine levels than did CD8(+) T cells. Analysis of EBV-specific T cell responses using autologous DCs transfected with mRNA might provide a comprehensive tool for monitoring EBV infection and new insights into the pathogenesis of EBV-associated diseases. PMID:26023769

  19. Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure

    PubMed Central

    Attar, Nahid; Sanders, Corron

    2015-01-01

    Background Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF. Method Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls. Results Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups–non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL. Summary/Conclusions While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting. PMID:26393924

  20. Molecular Typing and Epidemiology Profiles of Human Adenovirus Infection among Paediatric Patients with Severe Acute Respiratory Infection in China

    PubMed Central

    Li, Yamin; Zhou, Weimin; Zhao, Yanjie; Wang, Yanqun; Xie, Zhengde; Lou, Yongliang; Tan, Wenjie

    2015-01-01

    Background Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. Objective To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. Study Design Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. Results and Conclusions In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV. PMID:25856575

  1. An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection.

    PubMed

    De Fino, Chiara; Nociti, Viviana; Modoni, Anna; Bizzarro, Alessandra; Mirabella, Massimiliano

    2016-01-01

    We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome. PMID:26856946

  2. [Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

    PubMed

    Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

    2009-01-01

    The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic. PMID:19240010

  3. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  4. Management of acute respiratory infections by community health volunteers: experience of Bangladesh Rural Advancement Committee (BRAC).

    PubMed Central

    Hadi, Abdullahel

    2003-01-01

    OBJECTIVE: To assess the role of management practices for acute respiratory infections (ARIs) in improving the competency of community health volunteers in diagnosing and treating acute respiratory infections among children. METHODS: Data were collected by a group of research physicians who observed the performance of a sample of 120 health volunteers in 10 sub-districts in Bangladesh in which Bangladesh Rural Advancement Committee (BRAC) had run a community-based ARI control programme since mid-1992. Standardized tests were conducted until the 95% interphysician reliability on the observation of clinical examination was achieved. FINDINGS:The sensitivity, specificity, and overall agreement rates in diagnosing and treating ARIs were significantly higher among the health volunteers who had basic training and were supervised routinely than among those who had not. CONCLUSION: Diagnosis and treatment of ARIs at the household level in developing countries are possible if intensive basic training and the close supervision of service providers are ensured. PMID:12764514

  5. A case of severe thrombocytopaenia associated with acute HIV-1 infection.

    PubMed

    Aoki, Ami; Moro, Hiroshi; Watanabe, Takayuki; Asakawa, Katsuaki; Miura, Satoru; Moriyama, Masato; Tanabe, Yoshinari; Kagamu, Hiroshi; Narita, Ichiei

    2015-03-01

    A 23-year-old man was admitted to our hospital with severe thrombocytopaenia. He had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV infection by means of HIV RNA viral load testing and HIV-associated thrombocytopaenia. Although his thrombocytopaenia improved immediately with short-term dexamethasone therapy, this effect was not sustained after cessation of therapy. Antiretroviral therapy including raltegravir was initiated, and the patient recovered from severe thrombocytopaenia within several days. The findings from this case suggest that acute HIV infection should be suspected with unexplained thrombocytopaenia, and that antiretroviral therapy is the treatment of choice for severe HIV-associated thrombocytopaenia, even when in the early period following acquisition of the virus. PMID:24737880

  6. Acute lower motor neuron syndrome and spinal cord gray matter hyperintensities in HIV infection

    PubMed Central

    Wilson, Michael R.; Chad, David A.; Venna, Nagagopal

    2015-01-01

    Objective: To describe a novel manifestation of lower motor neuron disease in patients with well-controlled HIV infection. Methods: A retrospective study was performed to identify HIV-positive individuals with acute, painful lower motor neuron diseases. Results: Six patients were identified with HIV and lower motor neuron disease. Two patients met the inclusion criteria of well-controlled, chronic HIV infection and an acute, painful, unilateral lower motor neuron paralytic syndrome affecting the distal portion of the upper limb. These patients had segmental T2-hyperintense lesions in the central gray matter of the cervical spinal cord on MRI. One patient stabilized and the second patient improved with immunomodulatory therapy. Conclusions: This newly described syndrome expands the clinical spectrum of lower motor neuron diseases in HIV. PMID:26015990

  7. Acute hepatitis C infection in HIV-negative men who have sex with men.

    PubMed

    McFaul, K; Maghlaoui, A; Nzuruba, M; Farnworth, S; Foxton, M; Anderson, M; Nelson, M; Devitt, E

    2015-06-01

    Acute hepatitis C infection is recognized in HIV-infected men who have sex with men (MSM), but the risk in HIV-negative MSM remains unclear. We evaluated a population of MSM with acute hepatitis C. From January 2010 to May 2014, all cases of HCV antibody positive HIV-negative MSM were identified. European AIDS Network criteria were applied to determine acute infection, and 44 individuals fulfilled the criteria for acute hepatitis C. Ten were RNA negative at baseline and classed as prior spontaneous clearance. 15 (34.1%) had a previously negative HCV antibody within 1 year. 11 (25.0%) had significant elevation in ALT levels, and 18 (40.9%) were clinically diagnosed from risk exposure and history. Median age was 37 years (range 24-75). 41 (93.2%) individuals reported unprotected anal sex, 36 with (87.8%) both insertive and receptive intercourse, 4 (9.8%) with receptive intercourse, 1 (2.4%) with insertive intercourse, and no data were recorded for 3 (7.3%) patients. Individuals had an average of 7.3 reported (median 2, range 1-100) partners. 12 (27.3%) engaged in group sex, 11 (25.0%) practised fisting, 11 (25.0%) admitted using drugs during sexual activity, 16 (36.4%) reported nasal, and 9 (20.5%) reported injection drug use. 14 (31.8)% had unprotected sex whilst under the influence of recreational drugs. 29 individuals were aware of a partner's status. 2 (4.5%) individuals had sexual contact with a known HCV monoinfected partner, 13 (29.5%) with a HIV monoinfected partner and 6 (13.6%) with a HCV/HIV coinfected partner. 9 (20.5%) reported a partner/partners with no known infection. No data were available in 14 (31.8%) individuals. 13 (29.5%) individuals had a coexisting STI at the time of acute HCV diagnosis. 8 (18.2%) received HIV postexposure prophylaxis (PEP) within the 6 months prior to the HCV diagnosis (2 were participants in a HIV pre-exposure prophylaxis trial). 15 (34.1%) individuals achieved spontaneous clearance of HCV, and 11 patients received HCV

  8. Evaluation of a commercial dengue NS1 antigen-capture ELISA for laboratory diagnosis of acute dengue virus infection.

    PubMed

    Kumarasamy, V; Wahab, A H Abdul; Chua, S K; Hassan, Z; Chem, Y K; Mohamad, M; Chua, K B

    2007-03-01

    A commercial dengue NS1 antigen-capture ELISA was evaluated to demonstrate its potential application for early laboratory diagnosis of acute dengue virus infection. Dengue virus NS1 antigen was detected in 199 of 213 acute serum samples from patients with laboratory confirmation of acute dengue virus infection but none of the 354 healthy blood donors' serum specimens. The dengue NS1 antigen-capture ELISA gave an overall sensitivity of 93.4% (199/213) and a specificity of 100% (354/354). The sensitivity was significantly higher in acute primary dengue (97.3%) than in acute secondary dengue (70.0%). The positive predictive value of the dengue NS1 antigen-capture ELISA was 100% and negative predictive value was 97.3%. Comparatively, virus isolation gave an overall positive isolation rate of 68.1% with a positive isolation rate of 73.9 and 31.0% for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 66.7% with a detection rate of 65.2 and 75.9% for acute primary dengue and acute secondary dengue, respectively. The results indicate that the commercial dengue NS1 antigen-capture ELISA may be superior to virus isolation and RT-PCR for the laboratory diagnosis of acute dengue infection based on a single serum sample. PMID:17140671

  9. Topical versus Systemic Antibiotics in the Treatment of Acute Superficial Skin Infections

    PubMed Central

    Belcon, Michael C.

    1979-01-01

    Use of antibiotics in some superficial skin infections is examined. The choice of a route of administration is dependent on a number of factors, including the site and extent of skin lesions, frequency of recurrence, and clinical and immunological state of the host. However, the consensus of various studies on the subject seem to indicate a preference for the systemic route in acute infectious dermatoses. PMID:423278

  10. Dalbavancin for the treatment of acute bacterial skin and skin structure infections.

    PubMed

    Esposito, Silvano; Noviello, Silvana; Leone, Sebastiano

    2015-12-01

    Dalbavancin is a novel parenteral lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Dalbavancin is highly active against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has a prolonged half-life that allows for once weekly dosing. Phase III trials have demonstrated non-inferiority compared with vancomycin/linezolid in the treatment of ABSSSIs, including those sustained by MRSA. PMID:26700080

  11. Liver infection caused by Coniothyrium fuckelii in a patient with acute myelogenous leukemia.

    PubMed Central

    Kiehn, T E; Polsky, B; Punithalingam, E; Edwards, F F; Brown, A E; Armstrong, D

    1987-01-01

    A case of liver infection caused by Coniothyrium fuckelii is described in a patient with acute myelogenous leukemia. This fungus is found in the soil and can be a pathogen of plants. Coniothyrium spp. are members of the order Sphaeropsidales, an order composed of fungi whose conidiomata are usually pycnidia with the conidiogenous hymenium lining the walls of the locule. Coniothyrium spp. must be differentiated from Phoma spp. and Hendersonula spp., the two most commonly isolated members of the Sphaeropsidales. Images PMID:3480895

  12. Acute hepatitis C infection in a renal transplant recipient: primacy of the liver or kidney?

    PubMed Central

    Althaf, Mohammed Mahdi; Abdelsalam, Mohamed Said; Rashwan, Mohamed; Nadri, Quaid

    2014-01-01

    We present a case where a renal transplant recipient contracted chronic hepatitis C virus (HCV) infection post-transplantation. The disease progressed and deteriorated leading to fibrosing cholestatic hepatitis that mandated treatment. Treatment with pegylated interferon α-2a and ribavirin was successful in salvaging the liver and eradicating the virus but as a consequence lead to treatment-resistant acute rejection and loss of the renal allograft. PMID:24907214

  13. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children

    PubMed Central

    Carballal, Guadalupe; Videla, Cristina; Misirlian, Alicia; Requeijo, Paula V; Aguilar, María del Carmen

    2002-01-01

    Background Adenoviruses are the second most prevalent cause of acute lower respiratory infection of viral origin in children under four years of age in Buenos Aires, Argentina. The purpose of this study was to analyze the clinical features and outcome of acute lower respiratory infection associated with different adenovirus genotypes in children. Methods Twenty-four cases of acute lower respiratory infection and adenovirus diagnosis reported in a pediatric unit during a two-year period were retrospectively reviewed. Adenovirus was detected by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17 isolates was studied by restriction enzyme analysis with Bam HI and Sma I. Results Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%. Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7% (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 ±; 6 months, and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71% of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases; tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other respiratory viruses were negative. During hospitalization, fatality rate was 16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus, fatality rate for adenovirus type 7 reached 28.6% (4/14). Conclusions These results show the predominance of adenovirus 7 and high lethality associated with the genomic variants 7h and 7i in children hospitalized with acute lower respiratory infection. PMID:12184818

  14. Complete Genome Sequence of a Novel Human WU Polyomavirus Isolate Associated with Acute Respiratory Infection

    PubMed Central

    Dehority, Walter N.; Schwalm, Kurt C.; Young, Jesse M.; Gross, Stephen M.; Schroth, Gary P.; Young, Stephen A.

    2016-01-01

    We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, NM040708, collected from a patient with an acute respiratory infection in New Mexico. The double-stranded DNA (dsDNA) genome of NM040708 is 5,229 bp in length and differs from the WUPyV reference with accession no. NC_009539 by 6 nucleotides and 2 amino acids. PMID:27151782

  15. Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection ▿ †

    PubMed Central

    Liu, Pinghuang; Overman, R. Glenn; Yates, Nicole L.; Alam, S. Munir; Vandergrift, Nathan; Chen, Yue; Graw, Frederik; Freel, Stephanie A.; Kappes, John C.; Ochsenbauer, Christina; Montefiori, David C.; Gao, Feng; Perelson, Alan S.; Cohen, Myron S.; Haynes, Barton F.; Tomaras, Georgia D.

    2011-01-01

    Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection. PMID:21865397

  16. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  17. Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians

    PubMed Central

    Markanday, Anurag

    2015-01-01

    Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein have traditionally been used as markers for inflammation and as a measure of “sickness index” in infectious and noninfectious conditions. In the last decade, more data have become available on the wider and more specific role for these markers in the management of complex infections. This includes the potential role in early diagnosis, in differentiating infectious from noninfectious causes, as a prognostic marker, and in antibiotic guidance strategies. A better defined role for biological markers as a supplement to clinical assessment may lead to more judicious antibiotic prescriptions, and it has the potential for a long-term favorable impact on antimicrobial stewardship and antibiotic resistance. Procalcitonin as a biological marker has been of particular interest in this regard. This review examines the current published evidence and summarizes the role of various acute-phase markers in infections. A MEDLINE search of English-language articles on acute-phase reactants and infections published between 1986 and March 2015 was conducted. Additional articles were also identified through a search of references from the retrieved articles, published guidelines, systematic reviews, and meta-analyses. PMID:26258155

  18. EFFECTS OF IMMUNOSUPPRESSION WITH CYCLOPHOSPHAMIDE ON ACUTE MURINE CYTOMEGALOVIRUS INFECTION AND VIRUS-AUGMENTED NATURAL KILLER CELL ACTIVITY

    EPA Science Inventory

    The effects of cyclophosphamide (CY) treatment on acute murine cytomegalovirus (MCMV) infection were studied to explore the potential usefulness of MCMV as a means of detecting immune dysfunction and to identify host defense mechanisms important for protection against MCMV.

  19. Acute delayed infection: increased risk in failed metal on metal total hip arthroplasty.

    PubMed

    Prieto, Hernan A; Berbari, Elie F; Sierra, Rafael J

    2014-09-01

    Adverse local tissue reactions occurring in metal-on-metal total hip arthroplasty (MoM THA) could potentially lead to secondary failure modes such as dislocation or infection. The authors report a series of 124 patients treated with MoM hip arthroplasty between 2006 and 2010 with a minimum follow-up of 3 years. Eight hips presented with acute delayed or late periprosthetic joint infection (PJI) (defined as an infection occurring after 3 months in an otherwise well functioning implant). The rate of infection observed was higher than expected, almost 4 times higher (5.6%) compared to previous historical cohorts from our institution (1.3%). This high risk of infection in patients with DePuy ASR implants requires further study but we theorize that the increased prevalence of infection could be due to a combination of particulate debris, molecular (rather than particulate) effects of Co and Cr ions on soft tissues, and/or products of corrosion that may change the local environment predisposing to infection. PMID:24851788

  20. Validating a decision tree for serious infection: diagnostic accuracy in acutely ill children in ambulatory care

    PubMed Central

    Verbakel, Jan Y; Lemiengre, Marieke B; De Burghgraeve, Tine; De Sutter, An; Aertgeerts, Bert; Bullens, Dominique M A; Shinkins, Bethany; Van den Bruel, Ann; Buntinx, Frank

    2015-01-01

    Objective Acute infection is the most common presentation of children in primary care with only few having a serious infection (eg, sepsis, meningitis, pneumonia). To avoid complications or death, early recognition and adequate referral are essential. Clinical prediction rules have the potential to improve diagnostic decision-making for rare but serious conditions. In this study, we aimed to validate a recently developed decision tree in a new but similar population. Design Diagnostic accuracy study validating a clinical prediction rule. Setting and participants Acutely ill children presenting to ambulatory care in Flanders, Belgium, consisting of general practice and paediatric assessment in outpatient clinics or the emergency department. Intervention Physicians were asked to score the decision tree in every child. Primary outcome measures The outcome of interest was hospital admission for at least 24 h with a serious infection within 5 days after initial presentation. We report the diagnostic accuracy of the decision tree in sensitivity, specificity, likelihood ratios and predictive values. Results In total, 8962 acute illness episodes were included, of which 283 lead to admission to hospital with a serious infection. Sensitivity of the decision tree was 100% (95% CI 71.5% to 100%) at a specificity of 83.6% (95% CI 82.3% to 84.9%) in the general practitioner setting with 17% of children testing positive. In the paediatric outpatient and emergency department setting, sensitivities were below 92%, with specificities below 44.8%. Conclusions In an independent validation cohort, this clinical prediction rule has shown to be extremely sensitive to identify children at risk of hospital admission for a serious infection in general practice, making it suitable for ruling out. Trial registration number NCT02024282. PMID:26254472

  1. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  2. Acute viral infections with combined involvement of the respiratory and gastrointestinal tracts in children. Therapy with interferon.

    PubMed

    Dondurei, E A; Osidak, L V; Golovacheva, E G; Golovanova, A K; Amosova, I V; Gladchenko, L N

    2009-08-01

    We evaluated the percent of acute respiratory viral infections with gastrointestinal syndrome in the structure of morbidity in babies aging 6 months and elder. Therapeutic efficiency and safety of anaferon (pediatric formuation) as a component of complex therapy of acute respiratory viral infections with involvement of the gastrointestinal tract were proven; more rapid disappearance of all symptoms and improvement of the immune status parameters were demonstrated. PMID:20027348

  3. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  4. Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

    PubMed

    Laine, Outi K; Koskela, Sirpa M; Outinen, Tuula K; Joutsi-Korhonen, Lotta; Huhtala, Heini; Vaheri, Antti; Hurme, Mikko A; Jylhävä, Juulia; Mäkelä, Satu M; Mustonen, Jukka T

    2014-09-01

    Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection. PMID:24751477

  5. A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

    PubMed Central

    Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

    2011-01-01

    BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

  6. Critical role for the AIM2 inflammasome during acute central nervous system bacterial infection

    PubMed Central

    Hanamsagar, Richa; Aldrich, Amy; Kielian, Tammy

    2014-01-01

    Interleukin-1β (IL-1β) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1β production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated, speck-like, caspase-1 recruiting domain-containing protein), and pro-caspase-1. Here we utilized NLRP3, ASC, and caspase-1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase-1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to WT animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1β, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1β, since these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1β release and survival during acute CNS S. aureus infection. PMID:24484406

  7. A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates

    PubMed Central

    Yokoe, Deborah S.; Anderson, Deverick J.; Berenholtz, Sean M.; Calfee, David P.; Dubberke, Erik R.; Ellingson, Katherine D.; Gerding, Dale N.; Haas, Janet P.; Kaye, Keith S.; Klompas, Michael; Lo, Evelyn; Marschall, Jonas; Mermel, Leonard A.; Nicolle, Lindsay E.; Salgado, Cassandra D.; Bryant, Kristina; Classen, David; Crist, Katrina; Deloney, Valerie M.; Fishman, Neil O.; Foster, Nancy; Goldmann, Donald A.; Humphreys, Eve; Jernigan, John A.; Padberg, Jennifer; Perl, Trish M.; Podgorny, Kelly; Septimus, Edward J.; VanAmringe, Margaret; Weaver, Tom; Weinstein, Robert A.; Wise, Robert; Maragakis, Lisa L.

    2014-01-01

    Since the publication of “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals” in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS). PMID:25026611

  8. In vivo infection of IgG-containing cells by Jembrana disease virus during acute infection

    SciTech Connect

    Desport, Moira; Tenaya, I.W. Masa; McLachlan, Alexander; McNab, Tegan J.; Rachmat, Judhi; Hartaningsih, Nining; Wilcox, Graham E.

    2009-10-25

    Jembrana disease virus (JDV) is an unusual bovine lentivirus which causes a non-follicular proliferation of lymphocytes, a transient immunosuppression and a delayed humoral response in infected Bali cattle in Indonesia. A double-immunofluorescent labeling method was developed to identify the subset of mononuclear cells in which the viral capsid protein could be detected. Viral antigen was present in pleomorphic centroblast-like cells which were identified as IgG-containing cells, including plasma cells, in lymphoid tissues. There was no evidence of infection of CD3{sup +} T-cells or MAC387{sup +} monocytes in tissues but large vacuolated cells with a macrophage-like morphology in the lung were found to contain viral antigen although they could not be shown conclusively to be infected. The tropism of JDV for mature IgG-containing cells may be relevant to understanding the pathogenesis of Jembrana disease, the delayed antibody responses and the genetic composition of this atypical lentivirus.

  9. Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute myelogenous leukemia.

    PubMed

    Iwen, P C; Tarantolo, S R; Sutton, D A; Rinaldi, M G; Hinrichs, S H

    2000-09-01

    Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola. PMID:10970386

  10. Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia

    PubMed Central

    Tehrani, Shabnam; Hemmatian, Marjan

    2016-01-01

    Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. Conclusion: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported. PMID:27403180

  11. Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

    PubMed Central

    Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

    2016-01-01

    The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

  12. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.

    PubMed

    Ballen, Karen; Woo Ahn, Kwang; Chen, Min; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Antin, Joseph; Bhatt, Ami S; Boeckh, Michael; Chen, George; Dandoy, Christopher; George, Biju; Laughlin, Mary J; Lazarus, Hillard M; MacMillan, Margaret L; Margolis, David A; Marks, David I; Norkin, Maxim; Rosenthal, Joseph; Saad, Ayman; Savani, Bipin; Schouten, Harry C; Storek, Jan; Szabolcs, Paul; Ustun, Celalettin; Verneris, Michael R; Waller, Edmund K; Weisdorf, Daniel J; Williams, Kirsten M; Wingard, John R; Wirk, Baldeep; Wolfs, Tom; Young, Jo-Anne H; Auletta, Jeffrey; Komanduri, Krishna V; Lindemans, Caroline; Riches, Marcie L

    2016-09-01

    Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and <.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes. PMID:27343716

  13. Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute Mumps Infection

    PubMed Central

    Malaiyan, Jeevan; Ramanan, Padmasani Venkat; Subramaniam, Dinesh; Menon, Thangam

    2016-01-01

    Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases), 40 healthy subjects (20 pediatric and 20 adults) and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's rank correlation coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67) were positive for mumps IgG. We found that IFN-γ, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of mumps parotitis. PMID:27293364

  14. Progress in Treatment of Viral Infections in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Moschovi, Maria; Adamaki, Maria; Vlahopoulos, Spiros A.

    2016-01-01

    In children, the most commonly encountered type of leukemia is acute lymphoblastic leukemia (ALL). An important source of morbidity and mortality in ALL are viral infections. Even though allogeneic transplantations, which are often applied also in ALL, carry a recognized risk for viral infections, there are multiple factors that make ALL patients susceptible to viral infections. The presence of those factors has an influence in the type and severity of infections. Currently available treatment options do not guarantee a positive outcome for every case of viral infection in ALL, without significant side effects. Side effects can have very serious consequences for the ALL patients, which include nephrotoxicity. For this reason a number of strategies for personalized intervention have been already clinically tested, and experimental approaches are being developed. Adoptive immunotherapy, which entails administration of ex vivo grown immune cells to a patient, is a promising approach in general, and for transplant recipients in particular. The ex vivo grown cells are aimed to strengthen the immune response to the virus that has been identified in the patients’ blood and tissue samples. Even though many patients with weakened immune system can benefit from progress in novel approaches, a viral infection still poses a very significant risk for many patients. Therefore, preventive measures and supportive care are very important for ALL patients. PMID:27471584

  15. Ligand Induction of Retinoic Acid Receptors Alters an Acute Infection by Murine Cytomegalovirus†

    PubMed Central

    Angulo, Ana; Chandraratna, Roshantha A. S.; LeBlanc, James F.; Ghazal, Peter

    1998-01-01

    Here we report that administration of retinoids can alter the outcome of an acute murine cytomegalovirus (MCMV) infection. We show that a crucial viral control element, the major immediate-early enhancer, can be activated by retinoic acid (RA) via multiple RA-responsive elements (DR2) that bind retinoid X receptor-retinoic acid receptor (RAR) heterodimers with apparent dissociation constants ranging from 15 to 33 nM. Viral growth is dramatically increased upon RA treatment of infected tissue culture cells. Using synthetic retinoid receptor-specific agonists and antagonists, we provide evidence that RAR activation in cells is required for mediating the response of MCMV to RA. Oral administration of RA to infected immunocompetent mice selectively exacerbates an infection by MCMV, while cotreatment with an RAR antagonist protects against the adverse effects of RA on MCMV infection. In conclusion, these chemical genetic experiments provide evidence that an RAR-mediated pathway can modulate in vitro and in vivo infections by MCMV. PMID:9573222

  16. Differentiation between viral and bacterial acute infections using chemiluminescent signatures of circulating phagocytes.

    PubMed

    Prilutsky, Daria; Shneider, Evgeni; Shefer, Alex; Rogachev, Boris; Lobel, Leslie; Last, Mark; Marks, Robert S

    2011-06-01

    Oftentimes the etiological diagnostic differentiation between viral and bacterial infections is problematic, while clinical management decisions need to be made promptly upon admission. Thus, alternative rapid and sensitive diagnostic approaches need to be developed. Polymorphonuclear leukocytes (PMNs) or phagocytes act as major players in the defense response of the host during an episode of infection, and thereby undergo functional changes that differ according to the infections. PMNs functional activity can be characterized by quantification and localization of respiratory burst production and assessed by chemiluminescent (CL) byproduct reaction. We have assessed the functional states of PMNs of patients with acute infections in a luminol-amplified whole blood system using the component CL approach. In this study, blood was drawn from 69 patients with fever (>38 °C), and diagnosed as mainly viral or bacterial infections in origin. Data mining algorithms (C4.5, Support Vector Machines (SVM) and Naïve Bayes) were used to induce classification models to distinguish between clinical groups. The model with the best predictive accuracy was induced using C4.5 algorithm, resulting in 94.7% accuracy on the training set and 88.9% accuracy on the testing set. The method demonstrated a high predictive diagnostic value and may assist the clinician one day in the distinction between viral and bacterial infections and the choice of proper medication. PMID:21517122

  17. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    PubMed Central

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  18. Surveillance of Acute Respiratory Infections Using Community-Submitted Symptoms and Specimens for Molecular Diagnostic Testing

    PubMed Central

    Goff, Jennifer; Rowe, Aaron; Brownstein, John S.; Chunara, Rumi

    2015-01-01

    Participatory systems for surveillance of acute respiratory infection give real-time information about infections circulating in the community, yet to-date are limited to self-reported syndromic information only and lacking methods of linking symptom reports to infection types. We developed the GoViral platform to evaluate whether a cohort of lay volunteers could, and would find it useful to, contribute self-reported symptoms online and to compare specimen types for self-collected diagnostic information of sufficient quality for respiratory infection surveillance. Volunteers were recruited, given a kit (collection materials and customized instructions), instructed to report their symptoms weekly, and when sick with cold or flu-like symptoms, requested to collect specimens (saliva and nasal swab). We compared specimen types for respiratory virus detection sensitivity (via polymerase-chain-reaction) and ease of collection. Participants were surveyed to determine receptivity to participating when sick, to receiving information on the type of pathogen causing their infection and types circulating near them. Between December 1 2013 and March 1 2014, 295 participants enrolled in the study and received a kit. Of those who reported symptoms, half (71) collected and sent specimens for analysis. Participants submitted kits on average 2.30 days (95 CI: 1.65 to 2.96) after symptoms began. We found good concordance between nasal and saliva specimens for multiple pathogens, with few discrepancies. Individuals report that saliva collection is easiest and report that receiving information about what pathogen they, and those near them, have is valued and can shape public health behaviors. Community-submitted specimens can be used for the detection of acute respiratory infection with individuals showing receptivity for participating and interest in a real-time picture of respiratory pathogens near them. PMID:26075141

  19. Plasticity of the Systemic Inflammatory Response to Acute Infection during Critical Illness: Development of the Riboleukogram

    PubMed Central

    Burykin, Anton; Ruan, Jianhua; Li, Qing; Schierding, William; Lin, Nan; Dixon, David; Zhang, Weixiong; Coopersmith, Craig M.; Dunne, W. Michael; Colonna, Marco; Ghosh, Bijoy K.; Cobb, J. Perren

    2008-01-01

    Background Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness. Methodology/Principal Findings A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram) for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor. Conclusions/Significance Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic background, gender, and

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

    PubMed Central

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

    2014-01-01

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

  1. Acute parvovirus B19 infection in identical twins unmasking previously unidentified hereditary spherocytosis.

    PubMed

    Forde, Donall G; Cope, Alison; Stone, Ben

    2014-01-01

    Identical Caucasian male twins, previously fit, presented 1 week apart with short histories of fever and lethargy. The twins were febrile at presentation with profound pancytopaenia and evidence of haemolysis. There was no rash or arthralgia. Both required multiple red cell transfusions. The twins had positive IgM serology for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19. EBV viral capsid antigen and Epstein-Barr nuclear antigen IgGs were also positive however, suggesting past EBV exposure. Parvovirus B19 DNA was detected from peripheral blood PCR; CMV and EBV DNA PCRs were negative. Convalescent serology demonstrated no evolution of the CMV serological response, that is no IgG to CMV developed which implies an initial non-specific polyclonal IgM response. The twins recovered fully over 7 days, the first with a course of prednisolone and the second spontaneously. They were diagnosed with hereditary spherocytosis on convalescent blood films. On further questioning, a family history of hereditary spherocytosis was eventually revealed. The twins' maternal grandmother was known to have the condition asymptomatically. Their mother had prior to this never been tested, but later bloods would reveal a compatible biochemical picture. PMID:25073523

  2. Acute parvovirus B19 infection in identical twins unmasking previously unidentified hereditary spherocytosis

    PubMed Central

    Forde, Donall G; Cope, Alison; Stone, Ben

    2014-01-01

    Identical Caucasian male twins, previously fit, presented 1 week apart with short histories of fever and lethargy. The twins were febrile at presentation with profound pancytopaenia and evidence of haemolysis. There was no rash or arthralgia. Both required multiple red cell transfusions. The twins had positive IgM serology for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19. EBV viral capsid antigen and Epstein-Barr nuclear antigen IgGs were also positive however, suggesting past EBV exposure. Parvovirus B19 DNA was detected from peripheral blood PCR; CMV and EBV DNA PCRs were negative. Convalescent serology demonstrated no evolution of the CMV serological response, that is no IgG to CMV developed which implies an initial non-specific polyclonal IgM response. The twins recovered fully over 7 days, the first with a course of prednisolone and the second spontaneously. They were diagnosed with hereditary spherocytosis on convalescent blood films. On further questioning, a family history of hereditary spherocytosis was eventually revealed. The twins’ maternal grandmother was known to have the condition asymptomatically. Their mother had prior to this never been tested, but later bloods would reveal a compatible biochemical picture. PMID:25073523

  3. EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets: LMP-specific CD4+ cytotoxic T cell recognition of EBV-transformed B cell lines.

    PubMed

    Haigh, Tracey A; Lin, Xiaorong; Jia, Hui; Hui, Edwin P; Chan, Anthony T C; Rickinson, Alan B; Taylor, Graham S

    2008-02-01

    The EBV-latent membrane proteins (LMPs) 1 and 2 are among only three viral proteins expressed in EBV-associated Hodgkin's lymphoma and nasopharyngeal carcinoma. Since these tumors are HLA class I and class II-positive, the LMPs could serve as both CD8+ and CD4+ T cell targets. In contrast to CD8 responses, very little is known about CD4 responses to LMPs. In this study, we describe CD4+ T cell clones defining four LMP1- and three LMP2-derived peptide epitopes and their restricting alleles. All clones produced Th1-like cytokines in response to peptide and most killed peptide-loaded target cells by perforin-mediated lysis. Although clones to different epitopes showed different functional avidities in peptide titration assays, avidity per se was a poor predictor of the ability to recognize naturally infected B lymphoblastoid cell lines (LCLs) expressing LMPs at physiologic levels. Some epitopes, particularly within LMP1, consistently mediated strong LCL recognition detectable in cytokine release, cytotoxicity, and outgrowth inhibition assays. Using cyclosporin A to selectively block cytokine release, we found that CD4+ T cell cytotoxicity is the key effector of LCL outgrowth control. We therefore infer that cytotoxic CD4+ T cells to a subset of LMP epitopes could have therapeutic potential against LMP-expressing tumors. PMID:18209060

  4. Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection

    PubMed Central

    Ren, Peijun; Sheng, Jun; Yan, Huajie; Zhang, Jing; Lin, Xin; Wang, Yongjin; Delpeyroux, Francis; Deubel, Vincent

    2009-01-01

    Background Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. Methodology/Findings We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. Conclusion Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was

  5. Early enteral feeding in severe acute pancreatitis: can it prevent secondary pancreatic (super) infection?

    PubMed

    Lehocky, P; Sarr, M G

    2000-01-01

    Sepsis continues to account for a second peak in mortality in patients with severe acute pancreatitis. The prevention of these septic complications and subsequent development of multiple organ dysfunction syndrome remains a major focus for investigators, yet despite considerable clinical and experimental work addressing its etiology, septic complications remain high. Several studies have been designed to demonstrate the mechanism of origin of these septic complications with an attempt to define strategies for their prevention to improve patient outcomes. There is clear evidence that the origin of this secondary bacterial infection arises from enteric bacterial translocation secondary to disruption of the gut mucosal barrier during acute pancreatitis. Strategies designed to prevent secondary pancreatic infection include aggressive fluid resuscitation to maximize organ perfusion, early systemic antibiotic treatment or selective gut decontamination, and recently attempts to block mediators of the systemic inflammatory response. This discussion will summarize our present understanding of the etiopathogenesis of secondary bacterial 'superinfection' of necrotizing pancreatitis and how the initiation of enteral feeding early in the course of acute pancreatitis may prove to be an effective means of preventing and/or reversing the breakdown of the gut mucosal defense barrier. PMID:11155001

  6. Prevalence of sapovirus infection among infant and adult patients with acute gastroenteritis in Tehran, Iran

    PubMed Central

    Romani, Sara; Azimzadeh, Pedram; Bozorgi, Sajad Majidizadeh; Zali, Narges; Jadali, Farzaneh

    2012-01-01

    Aim This study investigated the prevalence of sapovirus infections in patient with acute gastroenteritis in Tehran, Iran. Background Sapovirus, a member of the family Caliciviridae is one of the major causative agents of viral gastroenteritis affecting both children and adult individuals. There isn't enough data about prevalence and genotypes of sapovirus infection in Tehran, the capital city of Iran. Patients and methods A total of 42 fecal samples were collected from patients with acute gastroenteritis from May to July 2009. RT nested- PCR was performed for screening. To genotype the sapovirus isolates, some positive samples were subjected to phylogenetic analysis by sequencing of fragments of viral capsid gene region. Results Sapovirus was detected in 5 of 42 stool specimens from patients with acute gastroenteritis. Sapovirus detected in this study was clustered into only one distinct genogroup I/2. Sapovirus GI/2 was predominant. Conclusion Our results show that among the studied viruses responsible for this disease, sapovirus was a major viral isolate virus. PMID:24834197

  7. CD123 redirected multiple virus-specific T cells for acute myeloid leukemia.

    PubMed

    Zhou, Li; Liu, Xin; Wang, Xingbing; Sun, Zimin; Song, Xiao-Tong

    2016-02-01

    Hematopoietic stem cell transplantation (HSCT) has been increasingly used as a curative treatment for acute myeloid leukemia (AML). However, relapse rates after HSCT in complete remission (CR) are reported between 30% and 70%. In addition, numerous studies suggested that secondary viral infection from a variety of viruses including Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus (CMV) are among the most common causes of death post-HSCT. Currently, chimeric antigen receptor (CAR)-based T cells have been developed to treat AML in clinical studies, while virus-specific cytotoxic T cells (VST) have been proven to be able to effectively prevent or treat viral infection after HSCT. Thus it would be desirable to develop T cells with the ability of simultaneously targeting AML relapse and viral infection. In this article, we now describe the generation of VST cells that are engineered to express CAR for a specific AML cell-surface antigen CD123 (CD123-CAR-VST). Using Dendritic cells (DCs) pulsed with EBV, Adv, and CMV peptides as sources of viral antigens, we generated VST from A2 donor peripheral mononuclear cells (PBMC). VST were then transduced with retroviral vector encoding CD123-CAR to generate CD123-CAR-VST. We demonstrated that CD123-CAR-VST recognized EBV, Adv, and CMV epitopes and had HLA-restricted virus-specific cytotoxic effector function against EBV target. In addition, CD123-CAR-VST retained the specificity against CD123-positive AML cell lines such as MOLM13 and THP-1 in vitro. Thus our results suggested that CD123-CAR-VST might be a valuable candidate to simultaneously prevent or treat relapse and viral infection in AML HSCT recipients. PMID:26740053

  8. The effect of feeding endophyte-infected fescue on the acute phase response to lipopolysaccharide in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus heifers (n = 22; 292 ± 9.0 kg body weight) were paired by body weight and randomly placed on either an endophyte-infected (E+) or endophyte-free (E-) diet for 10 days to determine the influence of feeding endophyte-infected fescue on the physiological and acute phase responses of beef heifers ...

  9. Suppression of Swine NK Cell Function During Acute Infection with Foot-and-Mouth Disease Virus (FMDV)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and causes an economically devastating disease. This highly acute infection has multiple negative effects on the innate response, presumably contributing to the rapid spread of virus within the host. Understanding the regulation of in...

  10. Complication of Corticosteroid Treatment by Acute Plasmodium malariae Infection Confirmed by Small-Subunit rRNA Sequencing▿

    PubMed Central

    To, Kelvin K. W.; Teng, Jade L. L.; Wong, Samson S. Y.; Ngan, Antonio H. Y.; Yuen, Kwok-Yung; Woo, Patrick C. Y.

    2010-01-01

    We report a case of acute Plasmodium malariae infection complicating corticosteroid treatment for membranoproliferative glomerulonephritis in a patient from an area where P. malariae infection is not endemic. A peripheral blood smear showed typical band-form trophozoites compatible with P. malariae or Plasmodium knowlesi. SSU rRNA sequencing confirmed the identity to be P. malariae. PMID:20739487

  11. Mycoplasma hominis-Associated Parapharyngeal Abscess following Acute Epstein-Barr Virus Infection in a Previously Immunocompetent Adult ▿

    PubMed Central

    Kennedy, Karina J.; Prince, Sam; Makeham, Timothy

    2009-01-01

    Mycoplasma hominis most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an M. hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection. PMID:19641070

  12. Mycoplasma hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection in a previously immunocompetent adult.

    PubMed

    Kennedy, Karina J; Prince, Sam; Makeham, Timothy

    2009-09-01

    Mycoplasma hominis most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an M. hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection. PMID:19641070

  13. The acute phase protein serum amyloid A (SAA) as an inflammatory marker in equine influenza virus infection.

    PubMed

    Hultén, C; Sandgren, B; Skiöldebrand, E; Klingeborn, B; Marhaug, G; Forsberg, M

    1999-01-01

    The acute phase protein serum amyloid A (SAA) has proven potentially useful as an inflammatory marker in the horse, but the knowledge of SAA responses in viral diseases is limited. The aim of this study was to evaluate SAA as a marker for acute equine influenza A2 (H3N8) virus infection. This is a highly contagious, serious condition that inflicts suffering on affected horses and predisposes them to secondary bacterial infections and impaired performance. Seventy horses, suffering from equine influenza, as verified by clinical signs and seroconversion, were sampled in the acute (the first 48 h) and convalescent (days 11-22) stages of the disease, and SAA concentrations were determined. Clinical signs and rectal temperature were recorded. Secondary infections, that could have influenced SAA concentrations, were clinically suspected in 4 horses. SAA concentrations were higher in the acute stage than in the convalescent stage, and there was a statistically positive relationship between acute stage SAA concentrations and clinical signs and between acute stage SAA concentrations and maximal rectal temperature. Horses sampled early in the acute stage had lower SAA concentrations than those sampled later, indicating increasing concentrations during the first 48 h. There was a statistically positive relationship between convalescent SAA concentrations and degree of clinical signs during the disease process. The results of this investigation indicate that equine SAA responds to equine influenza infection by increasing in concentration during the first 48 h of clinical signs and returning to baseline within 11-22 days in uncomplicated cases. PMID:10918902

  14. [Epstein-Barr virus infection - life cycle, methods of diagnosis, associated diseases].

    PubMed

    Bocian, Joanna; Januszkiewicz-Lewandowska, Danuta

    2011-01-01

    Epstein-Barr virus (EBV) is a ubiquitous virus that infects about 90–95% of the adult population. EBV establishes life-long latent persistence. The virus is found to be the major cause of infectious mononucleosis but it has also been associated with development of endemic Burkitt’s lymphoma. Result of EBV infection is the most common complication in patients after transplantation which is a post-transplant lymphoproliferative disease. Strong associations between EBV infection and Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric carcinoma and carcinomas derived from smooth muscle tissue also exist. There is a hypothesis that there is an association between EBV infection and autoimmune and allergic diseases. EBV is a Herpesvirus family member; its genetic material has dsDNA form. There are two strains of EBV: A and B. The only host for EBV is human with target cells: B cells and epithelial cells. The life cycle of EBV consists of lytic and latent phases. In the latent phase three different patterns of gene expression are possible. Due to some circumstances EBV can undergo reactivation, which is an important issue in transplantology. The main methods of diagnosis of EBV infections are serological methods that detect certain specific antibodies and recently more popular molecular biological methods such as PCR or in situ hybridization. PMID:21677354

  15. Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays.

    PubMed

    Wesolowski, Laura G; Nasrullah, Muazzam; Coombs, Robert W; Rosenberg, Eric; Ethridge, Steven F; Hutchinson, Angela B; Dragavon, Joan; Rychert, Jennifer; Nolte, Frederick S; Madory, James E; Werner, Barbara G

    2016-01-01

    Background.  To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.  We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results.  From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions.  Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT. PMID:26798766

  16. Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays

    PubMed Central

    Wesolowski, Laura G.; Nasrullah, Muazzam; Coombs, Robert W.; Rosenberg, Eric; Ethridge, Steven F.; Hutchinson, Angela B.; Dragavon, Joan; Rychert, Jennifer; Nolte, Frederick S.; Madory, James E.; Werner, Barbara G.

    2016-01-01

    Background. To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods. We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results. From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions. Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT. PMID:26798766

  17. Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection

    PubMed Central

    Hosseini, Iraj; Gama, Lucio; Mac Gabhann, Feilim

    2015-01-01

    Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues – spleen, mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMC) – we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA) method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 “judges”; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a) consensus genes likely to contribute highly to the immune response; (b) genes that would contribute highly to the immune response only if certain assumptions are met – e.g. that the cell responds to relative expression change rather than absolute expression change; and (c) genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral replication

  18. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  19. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization. PMID:27125562

  20. Development of a resource model for infection prevention and control programs in acute, long term, and home care settings: conference proceedings of the Infection Prevention and Control Alliance.

    PubMed

    Morrison, Judith

    2004-02-01

    There is mounting concern about the impact of health care restructuring on the provision of infection prevention services across the health care continuum. In response to this, Health Canada hosted two meetings of Canadian infection control experts to develop a model upon which the resources required to support an effective, integrated infection prevention and control program across the health care continuum could be based. The final models project the IPCP needs as three full time equivalent infection control professionals/500 beds in acute care hospitals and one full time equivalent infection control professional/150-250 beds in long term care facilities. Non human resource requirements are also described for acute, long term, community, and home care settings. PMID:14755227

  1. Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura.

    PubMed

    Gangarossa, S; Romano, V; Munda, S E; Sciotto, A; Schilirò, G

    1995-08-01

    Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms. PMID:7628586

  2. The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis

    PubMed Central

    Lee, Dong Yun

    2008-01-01

    The oncogene latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) without a ligand drives proliferation of EBV-infected B cells. Its levels vary in cells of clonal populations by more than 100-fold, which leads to multiple distinct activities of the oncogene. At intermediate levels it drives proliferation, and at high levels it inhibits general protein synthesis by inducing phosphorylation of eukaryotic initiation factor 2α (eIF2α). We have found that LMP1 activates PERK to induce phosphorylation of eIF2α, which upregulates activating transcription factor 4 (ATF4) expression. ATF4, in turn, transactivates LMP1's own promoter. LMP1 activates not only PERK but also inositol requiring kinase 1 (IRE1) and ATF6, 3 pathways of the unfolded protein response (UPR). Increasing expression levels of LMP1 induced a dose-dependent increase in IRE1 activity, as measured by its “splicing” of XBP-1. These infected B cells secrete immunoglobins independent of the levels of LMP1, indicating that only a threshold level of XBP-1 is required for the secretion. These findings indicate that LMP1's activation of the UPR is a normal event in a continuum of LMP1's expression that leads both to stimulatory and inhibitory functions and regulates the physiology of EBV-infected B cells in multiple, unexpected modes. PMID:18042799

  3. Epstein-Barr virus-carrying B cells are large, surface IgM, IgD-bearing cells in normal individuals and acute malaria patients.

    PubMed Central

    Lam, K M; Whittle, H; Grzywacz, M; Crawford, D H

    1994-01-01

    In this study the presence of Epstein-Barr virus (EBV) carrying B lymphocytes in different B-cell subpopulations from peripheral blood was determined by spontaneous outgrowth which gives rise to lymphoblastoid cell lines. In healthy seropositive adults, the EBV-carrying B cell was predominantly within the IgM- and IgD-positive but not the IgG-positive subpopulations. Furthermore, these B lymphocytes were in the low-density (large cell) Percoll fraction. The IgM- and IgD-positive B cell phenotype suggests the EBV-carrying B cells to be circulating virgin B cells recently released from the bone marrow. These B cells have an estimated life span of only 6-8 weeks suggesting that long-term EBV persistence in the body may be the result of infection of a more primitive B-cell type. Similar experiments were carried out in children with acute malaria from the Gambia, West Africa, where Burkitt lymphoma (BL) is endemic in order to determine whether a population of EBV-carrying B cells could be identified which had a similar phenotype to the BL cell. The EBV-carrying B cells in this patient group were also found in the IgM-positive, IgG-negative B-cell subpopulation. The majority of these cells were found in the low-density (large cell) Percoll fraction although in some patients a proportion was derived from the high-density (small cell) fraction. This cellular phenotype is not representative of a BL cell. PMID:7959872

  4. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report

    PubMed Central

    Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  5. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report.

    PubMed

    Vitaliti, Giovanna; Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  6. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection

    PubMed Central

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  7. The Frequency of Enterobius Vermicularis Infections in Patients Diagnosed With Acute Appendicitis in Pakistan

    PubMed Central

    Ahmed, Muhammad Umer; Bilal, Muhammad; Anis, Khurram; Khan, Ali Mahmood; Fatima, Kaneez; Ahmed, Iqbal; Khatri, Ali Mohammad; Shafiq-ur-Rehman

    2015-01-01

    Introduction: The main aim of this study was to determine the frequency of Enterobius Vermicularis infections and other unique histopathological findings in patients diagnosed with acute appendicitis. Materials: This retrospective study was conducted in a tertiary care hospital of Karachi, Pakistan over a time period of 9 years from 2005 to 2013. The recorded demographic and histopathological data for the 2956 appendectomies performed during this time frame were extracted using a structured template form. Negative and incidental appendectomies were excluded from the study. Results: Out of the 2956 patients diagnosed with acute appendicitis, 84 (2.8%) patients had Enterobius Vermicularis infections. Malignancy (n=2, 0.1%) and infection with Ascaris (n=1, 0.1%) was found very rarely among the patients. Eggs in lumen (n=22, 0.7%), mucinous cystadenoma (n=28, 1.0%), mucocele (n=11, 0.4%), lymphoma (n=9, 0.3%), obstruction in lumen (n=17, 0.6%) and purulent exudate (n=37, 1.3%) were also seldom seen in the histopathological reports. Conclusion: Enterobius Vermicularis manifestation is a rare overall but a leading parasitic cause of appendicitis. Steps such as early diagnosis and regular de worming may help eradicate the need for surgeries. PMID:26156929

  8. Loss of neurovirulence is associated with reduction of cerebral capillary sequestration during acute Babesia bovis infection

    PubMed Central

    2013-01-01

    Background Severe neurological signs that develop during acute infection by virulent strains of Babesia bovis are associated with sequestration of infected erythrocytes in cerebral capillaries. Serial passage of virulent strains in cattle results in attenuated derivatives that do not cause neurologic disease. We evaluated whether serial passage also results in a loss of cerebral capillary sequestration by examining brain biopsies during acute disease and at necropsy. Findings Cerebral biopsies of spleen intact calves inoculated intravenously with a virulent or attenuated strain pair of B. bovis were evaluated for capillary sequestration at the onset of babesiosis and during severe disease. In calves infected with the virulent strain, there was a significant increase in sequestration between the first and second biopsy timepoint. The attenuated strain was still capable of sequestration, but at a reduced level, and did not change significantly between the first and second biopsy. Necropsy examination confirmed the second biopsy results and demonstrated that sequestration identified at necropsy reflects pathologic changes occurring in live animals. Conclusions Loss of neurovirulence after serial in vivo passage of the highly virulent T2Bo strain of B. bovis in splenectomized animals is associated with a significant reduction of cerebral capillary sequestration. Previous genomic analysis of this and two other strain pairs suggests that this observation could be related to genomic complexity, particularly of the ves gene family, rather than consistent gene specific differences. Additional experiments will examine whether differential gene expression of ves genes is also associated with reduced cerebral sequestration and neurovirulence in attenuated strains. PMID:23777713

  9. Mononeuropathy multiplex associated with acute parvovirus B19 infection: characteristics, treatment and outcome.

    PubMed

    Lenglet, Timothée; Haroche, Julien; Schnuriger, Aurélie; Maisonobe, Thierry; Viala, Karine; Michel, Yanne; Chelbi, Farhat; Grabli, David; Seror, Paul; Garbarg-Chenon, Antoine; Amoura, Zahir; Bouche, Pierre

    2011-07-01

    To describe the characteristics of peripheral neuropathy related to acute parvovirus B19 (B19V) infection. We reviewed clinical, electrophysiological and histological data of three patients with peripheral neuropathy and positive B19V detection (IgG, IgM and PCR) compatible with acute infection. The neuropathy fulfilled criteria for mononeuropathy multiplex (MM). It could be preceded by or concurrent with a limited purpuric eruption, but systemic manifestations were absent. The first neurological symptoms were always sensory and localized in a hand. Neuropathy was initially limited to a restricted sensory part of a nerve trunk territory. The course was subacute with successive and asymmetric injury of the limb and cranial nerves. Electromyographic study confirmed the diagnosis of MM with multifocal asymmetric sensory and motor axonal loss in two patients, whereas the neuropathy was purely sensory and limited to two nerves in the other patient. Nerve biopsies showed no evidence of necrotizing vasculitis but, in one patient, revealed a lymphocytic perivascular infiltrate evocative of hypersensitivity vasculitis secondary to an infectious agent. Intravenous immunoglobulin (IVIg) was systematically administered. Long-term outcome was good but with incomplete sensory recovery and, for one patient, persistence of a functional disability. B19 V infection should be considered in the etiological assessment of MM, especially in the event of a progressive sensory disorder in the hands and a concomitant history of rash. IVIg may be an effective treatment for this inflammatory disorder. PMID:21287183

  10. Superiority of West Nile Virus RNA Detection in Whole Blood for Diagnosis of Acute Infection.

    PubMed

    Lustig, Yaniv; Mannasse, Batya; Koren, Ravit; Katz-Likvornik, Shiri; Hindiyeh, Musa; Mandelboim, Michal; Dovrat, Sara; Sofer, Danit; Mendelson, Ella

    2016-09-01

    The current diagnosis of West Nile virus (WNV) infection is primarily based on serology, since molecular identification of WNV RNA is unreliable due to the short viremia and absence of detectable virus in cerebrospinal fluid (CSF). Recent studies have shown that WNV RNA can be detected in urine for a longer period and at higher concentrations than in plasma. In this study, we examined the presence of WNV RNA in serum, plasma, whole-blood, CSF, and urine samples obtained from patients diagnosed with acute WNV infection during an outbreak which occurred in Israel in 2015. Our results demonstrate that 33 of 38 WNV patients had detectable WNV RNA in whole blood at the time of diagnosis, a higher rate than in any of the other sample types tested. Overall, whole blood was superior to all other samples, with 86.8% sensitivity, 100% specificity, 100% positive predictive value, and 83.9% negative predictive value. Interestingly, WNV viral load in urine was higher than in whole blood, CSF, serum, and plasma despite the lower sensitivity than that of whole blood. This study establishes the utility of whole blood in the routine diagnosis of acute WNV infection and suggests that it may provide the highest sensitivity for WNV RNA detection in suspected cases. PMID:27335150

  11. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    PubMed

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  12. A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

    PubMed Central

    Margolick, Joseph B.; Apuzzo, Linda; Singer, Joel; Wong, Hubert; Lee, Terry; Gallant, Joel E.; El-Helou, Phillippe; Loutfy, Mona R.; Rachlis, Anita; Fraser, Christopher; Kasper, Kenneth; Tremblay, Cécile; Tossonian, Harout; Conway, Brian

    2015-01-01

    Background It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression. Methods People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART. Results One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms. Conclusions This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection. Trial Registration ClinicalTrials.gov NCT00106171 PMID:26600459

  13. Prolonged Activation of Virus-Specific CD8+T Cells after Acute B19 Infection

    PubMed Central

    2005-01-01

    Background Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. Methods and Findings The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. Conclusion This is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development. PMID:16253012

  14. Kinetics of acute infection with Toxoplasma gondii and histopathological changes in the duodenum of rats.

    PubMed

    Trevizan, Aline Rosa; Vicentino-Vieira, Suellen Laís; da Silva Watanabe, Paulo; Góis, Marcelo Biondaro; de Melo, Gessilda de Alcântara Nogueira; Garcia, João Luiz; José de Almeida Araújo, Eduardo; Sant'Ana, Débora de Mello Gonçales

    2016-06-01

    Toxoplasma gondii crosses the intestinal barrier to spread into the body. We investigate the intestinal wall and epithelial cells of the duodenum of rats infected with T. gondii during different time points of acute infection. Male Wistar rats, 60 days of age, were assigned into groups that were orally inoculated with 5000 sporulated oocysts T. gondii for 6 h (G6), 12 h (G12), 24 h (G24), 48 h (G48), 72 h (G72), 7 days (G7d), and 10 days (G10d). The control group (CG) received saline. The rats were killed and the duodenum was processed to obtain histological sections stained with hematoxylin and eosin, Periodic Acid Schiff, and Alcian blue (pH 2.5 and 1.0). Morphometry was performed on the layers of the intestinal wall and enterocytes, and the number of goblet cells and intraepithelial lymphocytes was counted. The data were compared by ANOVA considering 5% as level of significance. The infection provoked an increase in the width of villi and crypts; decrease in enterocyte height; increase in the smaller-diameter and reduction in the larger-diameter of the enterocytes nuclei, increased number of goblet cells secreting neutral (G6, G12 and G7d) and acidic (G7d and G10d) mucus, and increase in the number of intraepithelial lymphocytes (G48). The infected groups showed atrophy of the submucosa and muscular layers and the total wall. Acute infection with T. gondii caused morphological changes in the intestinal wall and epithelial cells of the duodenum in rats. PMID:26993084

  15. [Detection of Trypanosoma cruzi DNA in the placenta and fetuses of mice with Chagasic acute infection].

    PubMed

    Alarcón, Maritza; Pérez, Mary Carmen; Villarreal, Juana; Araujo, Sonia; Goncalves, Loredana; González, Anajulia; Moreno, Elio; Lugo-Yarbuh, Ana

    2009-09-01

    The objective of the present study was to detect the presence of Trypanosoma cruzi DNA in the placenta and fetal tissues of NMRI mice (Mus musculus) inoculated with 22 x 10(3) trypomastigotes metacyclic of the M/HOM/BRA/53/Y strain by intraperitoneal route. Mice were pregnant in the acute phase of the infection. The course of patent parasitemia by T. cruzi was evaluated before mating and during pregnancy. At day twenty of gestation, animals were sacrificed and the fetuses and their placentas were removed to evaluate T. cruzi infection. Samples of fetal placenta, heart and skeletal muscle were fixed in 10%, formalin, included in paraffin and stained with hematoxilin and eosin (HE). The histopathological study of sections of fetal tissues revealed inflammatory infiltrates with mononuclear and polymorphonuclear cells and without parasitism in these tissues. The amplification of T. cruzi DNA by Polymerase Chain Reaction (PCR) showed a positive reaction in 18% of placental tissue of pregnant infected mice. The samples of heart and skeletal muscle of the fetuses of mothers infected with T. cruzi did not show the presence T. cruzi DNA. The placenta and skeletal muscle of the fetuses analyzed by Peroxidase anti Peroxidase inmunostaining showed T. cruzi antigens in those tissues. Negative results by PCR in fetal tissues might be related with the virulence and tropism associated with the biological and genetic characteristic Of the T. cruzi strain used in the experimental infection of female mice. PMID:19961056

  16. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

    SciTech Connect

    Guillaume, Vanessa; Wong, K. Thong; Looi, R.Y.; Georges-Courbot, Marie-Claude; Barrot, Laura; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2009-05-10

    Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeV if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.

  17. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections

    PubMed Central

    Braido, F; Tarantini, F; Ghiglione, V; Melioli, G; Canonica, G W

    2007-01-01

    Respiratory tract infections (RTIs) represent a serious problem because they are one of the most common cause of human death by infection. The search for the treatment of those diseases has therefore a great importance. In this study we provide an overview of the currently available treatments for RTIs with particular attention to chronic obstructive pulmonary diseases exacerbations and recurrent respiratory infections therapy and a description of bacterial lysate action, in particular making reference to the medical literature dealing with its clinical efficacy. Those studies are based on a very large number of clinical trials aimed to evaluate the effects of this drug in maintaining the immune system in a state of alert, and in increasing the defences against microbial infections. From this analysis it comes out that bacterial lysates have a protective effect, which induce a significant reduction of the symptoms related to respiratory infections. Those results could be very interesting also from an economic point of view, because they envisage a reduction in the number of acute exacerbations and a shorter duration of hospitalization. The use of bacterial lysate could therefore represent an important means to achieve an extension of life duration in patients affected by respiratory diseases. PMID:18229572

  18. Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas

    PubMed Central

    Piccaluga, Pier Paolo; Navari, Mohsen; De Falco, Giulia; Ambrosio, Maria Raffaella; Lazzi, Stefano; Fuligni, Fabio; Bellan, Cristiana; Rossi, Maura; Sapienza, Maria Rosaria; Laginestra, Maria Antonella; Etebari, Maryam; Rogena, Emily A.; Tumwine, Lynnette; Tripodo, Claudio; Gibellini, Davide; Consiglio, Jessica; Croce, Carlo M.; Pileri, Stefano A.; Leoncini, Lorenzo

    2016-01-01

    Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown. In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative BL, to identify specific patterns relying on the differential expression and role of Epstein-Barr virus-encoded microRNAs. First, we found significant differences in the expression of viral microRNAs and in selected target genes. Among others, we identified LIN28B, CGNL1, GCET2, MRAS, PLCD4, SEL1L, SXX1, and the tyrosine kinases encoding STK10/STK33, all provided with potential pathogenetic significance. GCET2, also validated by immunohistochemistry, appeared to be a useful marker for distinguishing EBV-positive and EBV-negative cases. Further, we provided solid evidences that the EBV-encoded microRNAs (e.g. BART6) significantly mold the transcriptional landscape of Burkitt Lymphoma clones. In conclusion, our data indicated significant differences in the transcriptional profiles of EBV-positive and EBV-negative BL and highlight the role of virus encoded miRNA. PMID:26325594

  19. Acute Q fever infection in Thuringia, Germany, after burial of roe deer fawn cadavers (Capreolus capreolus): a case report

    PubMed Central

    Schleenvoigt, B.T.; Sprague, L.D.; Mertens, K.; Moog, U.; Schmoock, G.; Wolf, G.; Neumann, M.; Pletz, M.W.; Neubauer, H.

    2015-01-01

    We report on a case of a 48-year-old man who presented with acute Q fever infection after burying two fawn cadavers (Capreolus capreolus). Recent outbreaks of Q fever in Europe have been traced back to intensive goat breeding units, sheep flocks in the proximity of highly populated urban areas or to farmed deer. To our knowledge, this is the first case report describing Q fever infection in a human linked to roe deer as a source of infection. PMID:26566445

  20. Use of Noninvasive Parameters to Evaluate Swiss Webster Mice During Trypanosoma cruzi Experimental Acute Infection.

    PubMed

    Campos, Jerônimo D S; Hoppe, Luanda Y; Duque, Thabata L A; de Castro, Solange Lisboa; Oliveira, Gabriel M

    2016-04-01

    Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use noninvasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi) when compared to the noninfected group (NI): (1) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration, and social isolation; (2) significant decrease in body weight (Inf: 26.2 ± 2.6 g vs. NI: 34.2 ± 2.5 g) and in chow (1.5 ± 0.3 vs. 6.3 ± 0.5 mg) and water (2.4 ± 0.5 vs. 5.8 ± 0.7 ml) intake; (3) significant decrease of spontaneous activity as locomotor parameters: distance (0.64 ± 0.06 vs. 1.8 ± 0.13 m), velocity (1.9 ± 0.3 vs. 6.7 ± 1.5 cm/sec), and exploratory behavior by frequency (1.0 ± 0.5 vs. 5.7 ± 1.0 events) and duration (1.4 ± 0.3 vs. 5.1 ± 0.5 sec in central arena region); (4) significant increase in the PR (41.7 ± 8.7 vs. 27.6 ± 1.9 msec) and QT intervals (39.7 ± 2.0 vs. 27.5 ± 4.0 msec), and a decreased cardiac frequency (505 ± 52.8 vs. 774 ± 17.8 msec), showing a marked sinus bradycardia and an atrioventricular block. At 3 and 4 wpi, the surviving animals showed a tendency of recovery in body weight, food intake, locomotor activity, and exploratory interest. Through the use of noninvasive parameters, we were able to monitor the severity of the infection in individuals prior to death. Our perspective is the application of noninvasive methods to describe clinical signs over the course of acute infection complementing the preclinical evaluation of new agents, alone or in combination with benznidazole. PMID:26741817

  1. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells

    PubMed Central

    Waguespack, Yan; Figliozzi, Robert W.; Kharel, Madan K.; Zhang, Qiaojuan; Martin-Caraballo, Miguel

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  2. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells.

    PubMed

    Rochford, Kevin; Chen, Feng; Waguespack, Yan; Figliozzi, Robert W; Kharel, Madan K; Zhang, Qiaojuan; Martin-Caraballo, Miguel; Hsia, S Victor

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  3. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection

    PubMed Central

    Tan, Petrina; Lye, David C.; Yeo, Tun Kuan; Cheung, Carol Y.; Thein, Tun-Linn; Wong, Joshua G.; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C.; Leo, Yee-Sin; Teoh, Stephen C.

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x104], p < 0.001; 0.849 vs 0.658 [x104], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system. PMID:26603217

  4. Infection related renal impairment: a major cause of acute allograft dysfunction.

    PubMed

    Nampoory, Mangalathillam R N; Johny, Kaivilayil V; Costandy, Jamal N; Nair, Madhavan P; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa

    2003-06-01

    We prospectively analyzed the impact of post-transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up period, 52 patients expired and 64 lost on followup. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=or<0.01). Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR. PMID:15859909

  5. Burkholderia pseudomallei Colony Morphotypes Show a Synchronized Metabolic Pattern after Acute Infection

    PubMed Central

    Steinmetz, Ivo; Lalk, Michael

    2016-01-01

    Background Burkholderia pseudomallei is a water and soil bacterium and the causative agent of melioidosis. A characteristic feature of this bacterium is the formation of different colony morphologies which can be isolated from environmental samples as well as from clinical samples, but can also be induced in vitro. Previous studies indicate that morphotypes can differ in a number of characteristics such as resistance to oxidative stress, cellular adhesion and intracellular replication. Yet the metabolic features of B. pseudomallei and its different morphotypes have not been examined in detail so far. Therefore, this study aimed to characterize the exometabolome of B. pseudomallei morphotypes and the impact of acute infection on their metabolic characteristics. Methods and Principal Findings We applied nuclear magnetic resonance spectroscopy (1H-NMR) in a metabolic footprint approach to compare nutrition uptake and metabolite secretion of starvation induced morphotypes of the B. pseudomallei strains K96243 and E8. We observed gluconate production and uptake in all morphotype cultures. Our study also revealed that among all morphotypes amino acids could be classified with regard to their fast and slow consumption. In addition to these shared metabolic features, the morphotypes varied highly in amino acid uptake profiles, secretion of branched chain amino acid metabolites and carbon utilization. After intracellular passage in vitro or murine acute infection in vivo, we observed a switch of the various morphotypes towards a single morphotype and a synchronization of nutrient uptake and metabolite secretion. Conclusion To our knowledge, this study provides first insights into the basic metabolism of B. pseudomallei and its colony morphotypes. Furthermore, our data suggest, that acute infection leads to the synchronization of B. pseudomallei colony morphology and metabolism through yet unknown host signals and bacterial mechanisms. PMID:26943908

  6. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

    PubMed

    Tan, Petrina; Lye, David C; Yeo, Tun Kuan; Cheung, Carol Y; Thein, Tun-Linn; Wong, Joshua G; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C; Leo, Yee-Sin; Teoh, Stephen C

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system. PMID:26603217

  7. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  8. Fungal infection intensity and zoospore output of Atelopus zeteki, a potential acute chytrid supershedder.

    PubMed

    Direnzo, Graziella V; Langhammer, Penny F; Zamudio, Kelly R; Lips, Karen R

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially as they relate to

  9. Fungal Infection Intensity and Zoospore Output of Atelopus zeteki, a Potential Acute Chytrid Supershedder

    PubMed Central

    DiRenzo, Graziella V.; Langhammer, Penny F.; Zamudio, Kelly R.; Lips, Karen R.

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially

  10. Mesenteric lymph duct drainage attenuates acute lung injury in rats with severe intraperitoneal infection.

    PubMed

    Zhang, Yanmin; Zhang, Shukun; Tsui, Naiqiang

    2015-01-01

    The purpose of this study is to investigate the hypothesis that the mesenteric lymphatic system plays an important role in acute lung injury in a rat model induced by severe intraperitoneal infection. Male Wistar rats weighing 250∼300 g were randomly divided into 3 groups and subjected to sham operation, intraperitoneal infection, or mesenteric lymphatic drainage. The activity of diamine oxidase (DAO) and myeloperoxidase (MPO) were measured by enzymatic assay. The endotoxin levels in plasma, lymph, and bronchoalveolar lavage fluid (BALF) were evaluated using the limulus amoebocyte lysate reagent. The cytokines, adhesion factors, chemokines, and inflammatory factors were detected by ELISA. TLR-4, NF-kB, and IRAK-4 were analyzed by Western blotting. Compared with sham-operated rats, rats with intraperitoneal infection had increased MPO and decreased DAO activity in intestinal tissues. Mesenteric lymph drainage reduced the alterations in MPO and DAO activity induced by intraperitoneal infection. The MPO activity in pulmonary tissue and the permeability of pulmonary blood vessels were also increased, which were partially reversed by mesenteric lymph drainage. The endotoxin levels in lymphatic fluid and alveolar perfusion fluid were elevated after intraperitoneal infection but decreased to control levels after lymph drainage. No alterations in the levels of plasma endotoxin were observed. The number of neutrophils was increased in BALF and lymph in the infected rats, and was also reduced after drainage. Lymph drainage also decreased the levels of inflammatory cytokines, chemokines, and adhesion factors in the plasma, lymph, and BALF, as well as the levels of TLR-4, NF-kB, and IRAK-4 in pulmonary and intestinal tissues. The mesenteric lymphatic system is the main pathway involved in early lung injury caused by severe intraperitoneal infection, in which activation of the TLR-4 signal pathway may play a role. PMID:25537798

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

    PubMed Central

    Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R.; Valbuena, Gustavo; Walker, David H.; Bouyer, Donald H.

    2016-01-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11–12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14–19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

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

    PubMed

    Soong, Lynn; Mendell, Nicole L; Olano, Juan P; Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R; Valbuena, Gustavo; Walker, David H; Bouyer, Donald H

    2016-08-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

  13. Fatal Fast-Evolution of Nasopharyngeal Squamous Cell Carcinoma in an HIV Patient with EBV and HPV (-16 AND -33) in Blood Serum

    PubMed Central

    Sirera, Guillem; Videla, Sebastià; Romeu, Joan; Cañadas, MariPaz; Fernández, Maria-Teresa; Balo, Susana; Cirauqui, Beatriz; Darwich, Laila; Rey-Joly, Celestino; Clotet, Bonaventura

    2008-01-01

    Our case illustrates the first report of an HIV-infected patient with a nasopharyngeal squamous cell carcinoma with viremia by one Epstein-Barr virus (EBV) and seropositivity by two high risk oncogenic human papilloma viruses (HPV)-types (HPV-16 and HPV-33), previous to his death. This patient presented a fatal fast-evolution. PMID:18923693

  14. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology

    PubMed Central

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  15. Direct costs of acute respiratory infections in a pediatric long-term care facility.

    PubMed

    Murray, Meghan T; Heitkemper, Elizabeth; Jackson, Olivia; Neu, Natalie; Stone, Patricia; Cohen, Bevin; Saiman, Lisa; Hutcheon, Gordon; Larson, Elaine L

    2016-01-01

    Acute respiratory tract infections (ARI) are a major burden in pediatric long-term care. We analyzed the financial impact of ARI in 2012-2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non-respiratory viral season, $31 224 and $3242 per 1000 patient-days, respectively (P < 0·001). ARI are burdensome for pediatric long-term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention. PMID:26425787

  16. Identification of an acute-phase reactant in murine infections with Trypanosoma brucei.

    PubMed Central

    Shapiro, S Z; Black, S J

    1992-01-01

    A 42-kDa protein appeared at a much higher concentration in plasma from Trypanosoma brucei-resistant (C57BL/6) mice after infection than in plasma from trypanosome-susceptible (C3H/He) mice. This protein was purified by sequential steps of gel filtration, protein A-Sepharose affinity chromatography, isoelectric focusing, and ammonium sulfate precipitation. The purified protein was identified as a subunit of the acute-phase reactant haptoglobin. Causes of elevated plasma haptoglobin and its implications for resistance to trypanosomiasis are discussed. Images PMID:1500201

  17. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology.

    PubMed

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  18. [A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

    PubMed

    Oda, M; Udaka, F; Kubori, T; Oka, N; Kameyama, M

    2000-08-01

    A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case. PMID:11218707

  19. Acute Compartment Syndrome of the Foot due to Infection After Local Hydrocortisone Injection: A Case Report.

    PubMed

    Patil, Sampat Dumbre; Patil, Vaishali Dumbre; Abane, Sachin; Luthra, Rohit; Ranaware, Abhijit

    2015-01-01

    High-energy trauma associated with calcaneal fracture or Lisfranc fracture dislocation and midfoot crushing injuries are known causes of compartment syndrome in the foot. Suppurative infection in the deep osseofascial compartments can also cause compartment syndrome. We describe the case of a 29-year-old female who had developed a suppurative local infection that resulted in acute compartment syndrome after receiving a local hydrocortisone injection for plantar fasciitis. We diagnosed the compartment syndrome, and fasciotomy was promptly undertaken. After more than 2 years of follow-up, she had a satisfactory functional outcome without substantial morbidity. To our knowledge, no other report in the English-language studies has described compartment syndrome due to abscess formation after a local injection of hydrocortisone. The aim of our report was to highlight this rare, but serious, complication of a routine outpatient clinical procedure. PMID:24838218

  20. Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

    PubMed Central

    da Silva, Rosiane V.; Malvezi, Aparecida D.; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H.; Yamauchi, Lucy M.; Yamada-Ogatta, Sueli F.; Rizzo, Luiz V.; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  1. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    PubMed

    da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  2. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

    PubMed

    Gyarmati, P; Kjellander, C; Aust, C; Song, Y; Öhrmalm, L; Giske, C G

    2016-01-01

    Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID:26996149

  3. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  4. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia

    PubMed Central

    Gyarmati, P.; Kjellander, C.; Aust, C.; Song, Y.; Öhrmalm, L.; Giske, C. G.

    2016-01-01

    Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID:26996149

  5. Infection of human thymocytes by Epstein-Barr virus.

    PubMed

    Watry, D; Hedrick, J A; Siervo, S; Rhodes, G; Lamberti, J J; Lambris, J D; Tsoukas, C D

    1991-04-01

    The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated. PMID:1706754

  6. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    PubMed Central

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. The