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Now showing items 49 - 64 of 150

  • IMMUNOLOGICAL HERPES SIMPLEX VIRUS ANTIGENS AND METHODS FOR USE THEREOF

    The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved antiviral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.
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  • Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome

    Jerome, Keith R.   Diem, Kurt   Huang, Meei-Li   Selke, Stacy   Corey, Lawrence   Buchwald, Dedra  

    A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS. (C) 2011 Elsevier Inc. All rights reserved.
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  • Antimicrobial resistance prevention initiative - An update: Proceedings of an expert panel on resistance

    Moellering, Robert C., Jr.   Graybill, John R.   McGowan, John E., Jr.   Corey, Lawrence  

    Antimicrobial resistance is a growing problem that complicates the treatment of important nosocomial and community-acquired infections. It is a worldwide problem that spans the range of human pathogens, including bacteria, fungi, and viruses. This update from the Antimicrobial Resistance Prevention Initiative (ARPI) provides a review of some important trends in antibiotic, antifungal, and antiviral resistance. Areas of focus include multidrug-resistant bacteria in the hospital setting; the growing problem of community-acquired methicillin-resistant Staphylococcus aureus; triazole and polyene resistance in nosocomial infections caused by non-Candida albicans or Aspergillus species, and the utility of in vitro susceptibility testing for these fungal infections; antiviral resistance in alpha- or beta-herpesviruses causing genital herpes or cytomegalovirus infection in immunocompromised hosts; and concerns about a possible pandemic involving avian influenza A and the importance of minimizing emergence of resistant strains of this highly pathogenic virus. The challenges in each area are different, but the general keys to addressing the growing problem of antimicrobial resistance continue to be responsible antimicrobial stewardship and the development of newer antimicrobial agents. (c) 2007 Elsevier Inc. All rights reserved.
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  • Antimicrobial resistance prevention initiative--an update: proceedings of an expert panel on resistance.

    Moellering, Robert C Jr   Graybill, John R   McGowan, John E Jr   Corey, Lawrence  

    Antimicrobial resistance is a growing problem that complicates the treatment of important nosocomial and community-acquired infections. It is a worldwide problem that spans the range of human pathogens, including bacteria, fungi, and viruses. This update from the Antimicrobial Resistance Prevention Initiative (ARPI) provides a review of some important trends in antibiotic, antifungal, and antiviral resistance. Areas of focus include multidrug-resistant bacteria in the hospital setting; the growing problem of community-acquired methicillin-resistant Staphylococcus aureus; triazole and polyene resistance in nosocomial infections caused by non-Candida albicans or Aspergillus species, and the utility of in vitro susceptibility testing for these fungal infections; antiviral resistance in alpha- or beta-herpesviruses causing genital herpes or cytomegalovirus infection in immunocompromised hosts; and concerns about a possible pandemic involving avian influenza A and the importance of minimizing emergence of resistant strains of this highly pathogenic virus. The challenges in each area are different, but the general keys to addressing the growing problem of antimicrobial resistance continue to be responsible antimicrobial stewardship and the development of newer antimicrobial agents.
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  • Virus population homogenization following acute human immunodeficiency virus type 1 infection.

    Learn, Gerald H   Muthui, David   Brodie, Scott J   Zhu, Tuofu   Diem, Kurt   Mullins, James I   Corey, Lawrence  

    Understanding the properties of human immunodeficiency virus type 1 (HIV-1) variants capable of establishing infection is critical to the development of a vaccine against AIDS. Previous studies of men have shown that the HIV-1 env gene is homogeneous early in infection, leading to the suggestion that infection is established by a single transmitted variant. However, we report here that all of eight homosexual men evaluated beginning 3.7 to 9 weeks following onset of symptoms of acute infection harbored diverse virus populations in their blood, with median genetic distances averaging 1.08% in the env C2V5 region and 0.81% in the gag p17 gene. Within another 4.7 to 11 weeks, the variant lineage in env became more homogeneous, while gag sequences continued to diversify. Thus, the homogenization that has been reported to characterize acute infection is actually preceded by the replication of multiple virus variants. This early selective process focuses on viral properties within Env but not Gag p17. Hence, the viral homogeneity observed early in HIV-1 infection results from a selective process that occurs during the establishment of infection.
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  • Recombinant Glycoprotein Vaccine for the Prevention of Genital HSV-2 Infection

    Corey, Lawrence   Langenberg, Andria G. M.   Ashley, Rhoda   Sekulovich, Rose E.   Izu, Allen E.   Douglas, Jr, John M.   Handsfield, H. Hunter   Warren, Terri   Marr, Lisa   Tyring, Stephen   DiCarlo, Richard   Adimora, Adaora A.   Leone, Peter   Dekker, Cornelia L.   Burke, Rae Lyn   Leong, Wai Ping   Straus, Stephen E.   for the Chiron HSV Vaccine Study Group,  

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  • The Effect of Imatinib on Cytomegalovirus Reactivation in Hematopoietic Cell Transplantation RID C-2286-2008

    Travi, Giovanna   Pergam, Steven A.   Xie, Hu   Carpenter, Paul   Kiem, Hans-Peter   Corey, Lawrence   Boeckh, Michael J.  

    In vitro studies have shown possible antiviral effects of tyrosine kinase inhibitors. In a retrospective study, we show that use of the tyrosine kinase inhibitor imatinib does not appear to reduce cytomegalovirus reactivation during the first 100 days after transplantation in a cohort of hematopoietic cell transplant recipients.
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  • RAPID, EFFICIENT PURIFICATION OF HSV-SPECIFIC T-LYMPHOCYTES AND HSV ANTIGENS IDENTIFIED VIA SAME

    Described is a method of identifying an immunologically active antigen of a virus that attacks skin, as well as a method of enriching a population of lymphocytes for T lymphocytes that are specific to a virus that attacks skin. Also provided are HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection that have been identified via the methods of the invention. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.
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  • Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy.

    Gantt, Soren   Cattamanchi, Ashok   Krantz, Elizabeth   Magaret, Amalia   Selke, Stacy   Kuntz, Steven R   Huang, Meei-Li   Corey, Lawrence   Wald, Anna   Casper, Corey  

    BACKGROUND: Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective.; OBJECTIVE: To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs.; STUDY DESIGN: Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations.; RESULTS: HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naive persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naive persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL).; CONCLUSIONS: HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. Copyright =C2=A9 2014 Elsevier B.V. All rights reserved.
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  • Longitudinal study of herpes simplex virus type 2 infection using viral dynamic modelling RID B-6272-2012

    Crespi, Catherine M.   Cumberland, William G.   Wald, Anna   Corey, Lawrence   Blower, Sally  

    Objectives: Rates of reactivation of herpes simplex virus type 2 (HSV-2) change over time and these changes affect transmission and clinical management strategies. We conducted a longitudinal study of HSV-2 infection to quantify rates of change in HSV-2 reactivation, mucosal shedding and recurrences of genital lesions, using a newly available model of HSV within-host dynamics. Methods: A cohort of 18 women was studied at two time periods spaced 2 years apart. The cohort provided daily mucosal swabs for HSV PCR analysis for 10 weeks during each time period and recorded recurrences in diaries. We fit the model of HSV dynamics to the mucosal shedding data using Bayesian methods to produce estimates of HSV reactivation, shedding and longitudinal rates of change. The model was validated using a separate group of 67 individuals. Results: According to the viral dynamic modelling results, rates of HSV-2 reactivation from latency in the ganglia varied > 10-fold among the women, and were estimated to be >= 10% higher than rates of mucosal shedding episodes for many individuals. The mucosal shedding associated with each reactivation typically lasted 1-3 days. Reactivation frequency was estimated to be declining by three reactivations a year on average. The median number of recurrences, based on patient diaries, declined from 6.8 per year to 2.1 per year over the 2-year period. Conclusions: Rates of HSV-2 reactivation, shedding and recurrence generally decline over time but remain high in some individuals 4-5 years after primary infection. Viral dynamic modelling provides quantification of HSV infection that cannot be obtained by other methods.
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  • Clinical outcomes associated with respiratory virus detection before allogeneic hematopoietic stem cell transplant.

    Campbell, Angela P   Guthrie, Katherine A   Englund, Janet A   Farney, Robert M   Minerich, Elisa L   Kuypers, Jane   Corey, Lawrence   Boeckh, Michael  

    BACKGROUND: The management of respiratory virus infections prior to hematopoietic cell transplant (HCT) is difficult. We examined whether respiratory virus detection before HCT influenced the requirement for bronchoscopy, hospitalization, and overall survival following HCT.; METHODS: Pre-HCT and weekly post-HCT nasal washes were collected through day 100 from patients with and without symptoms. Samples were tested by multiplex polymerase chain reaction for respiratory syncytial virus, parainfluenza viruses 1-4, influenza A and B, human metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and bocavirus.; RESULTS: Of 458 patients, 116 (25%) had respiratory viruses detected pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR], 2.4; 95% confidence interval [CI], 1.3-4.5; P =3D .007) than patients with negative samples; this risk was also present with rhinovirus alone (aHR for mortality, 2.6; 95% CI, 1.2-5.5; P =3D .01). No difference in bronchoscopy incidence was seen in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8-2.0; P =3D .32). In symptomatic patients, those with respiratory viruses detected had increased overall mortality compared with patients without viruses detected (unadjusted HR, 3.5; 95% CI, 1.0-12.1; P =3D .05); among asymptomatic patients, detection of respiratory viruses was not associated with increased mortality.; CONCLUSIONS: These data support routine testing for respiratory viruses among symptomatic patients before HCT, and delay of transplant with virus detection when feasible, even for detection of rhinovirus alone. Further study is needed to address whether asymptomatic patients should undergo screening for respiratory virus detection before HCT. =C2=A9 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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  • A Prospective Cohort Study of Partner Testing for Herpes Simplex Virus and Sexual Behavior During Pregnancy

    Gardella, Carolyn   Daruthayan, Constance   Saracino, Misty   Drolette, Linda   Corey, Lawrence   Wald, Anna  

    Background. We investigated whether serotesting sexual partners of pregnant women for herpes simplex virus (HSV) improves adherence to safer-sex practices.Methods. A total of 287 HSV-2-seronegative pregnant women were recruited, and their partners were invited for HSV serologic testing. On the basis of test results, women were placed into 4 groups: those at risk for HSV-2 infection, those at risk for HSV-1 infection, those whose partner was not tested, and those not at risk for HSV infection. Women received safer-sex counseling and completed diaries of sexual activity.Results. Women in HSV-2-serodiscordant couples (ie, those in relationships in which they were at risk for HSV-2 acquisition) reported a smaller percentage of days with unprotected genital sex acts as compared to women who were not at risk (2% vs 8%; relative risk [RR], 0.3 [95% confidence interval {CI},.1-.8]; P =.002) and to women whose partners' HSV status was unknown (2% vs 11%; RR, 0.2 [95% CI,.1-.8]; P = .02). Women in HSV-1-serodiscordant couples showed no difference in the frequency of genital sex acts, unprotected genital sex acts, or oral sex acts as compared to those not at risk and to those whose partners' status was unknown.Conclusions. Pregnant women at known risk of HSV-2 acquisition by partner serotesting were less likely to engage in unprotected genital sex acts than HSV-2-seronegative women with partners who were negative or not tested.
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  • Infectious complications after autologous CD34-selected peripheral blood stem cell transplantation.

    Crippa, Fulvio   Holmberg, Leona   Carter, Rachel A   Hooper, Heather   Marr, Kieren A   Bensinger, William   Chauncey, Thomas   Corey, Lawrence   Boeckh, Michael  

    CD34 selection of peripheral hematopoietic blood stem cell products has been applied to reduce the risk of relapse after an autologous transplantation. However, CD34 selection is also associated with a significant reduction in T-cells, natural killer cells, and monocytes, and these reductions may influence immune reconstitution and thus increase the risk for infections. An increased incidence of cytomegalovirus (CMV) disease in patients receiving CD34-selected transplants has been reported. In this study, the incidence rate of infections other than CMV is reported in 32 patients who underwent myeloablative therapy followed by the infusion of CD34-selected autologous peripheral blood stem cells (PBSC) and compared to the rate in a contemporaneous group of 273 patients who received unselected autologous PBSC during the same time period. Infection surveillance and prevention strategies were identical between the 2 groups. More non-CMV infections occurred in the recipients of CD34-selected PBSC than in recipients of unselected PBSC (78% versus 30%, P < .0001). The differences in the rates of viral infections were mainly due to dermatomal and disseminated varicella-zoster virus (VZV) (any VZV, 26% versus 4%, P = .002; disseminated VZV, 11% versus 0.3%, P = .03) and parainfluenza 3 virus infections (13% versus 3%, P = .04). Bacterial infections were also more common among CD34-selected PBSC transplant recipients (34% versus 16%, P = .01), whereas fungal infections were not significantly different between the groups. In multivariable logistic regression models, the effect of CD34 selection on infection risk remained significant for viral infections and overall non-CMV infections. Infection-related mortality was not significantly different between the groups. In conclusion, the incidence of viral and bacterial infections appears to be increased in recipients of CD34-selected autologous PBSC transplants. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic work-up, and prevention strategies similar to those used in allogeneic recipients are warranted.
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  • Therapy for Human Immunodeficiency Virus Infection — What Have We Learned?

    Corey, Lawrence   Holmes, King K.  

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  • The Kinetics of Mucosal Herpes Simplex Virus-2 Infection in Humans: Evidence for Rapid Viral-Host Interactions

    Wald, Anna   Selke, Stacy   Corey, Lawrence   Magaret, Amalia  

    Background. Herpes simplex virus type 2 (HSV-2) reactivations in the genital tract are responsible for mucocutaneous lesions and transmission and manifest as discrete shedding episodes.Methods. We analyzed duration, peak copy number, and expansion and decay rates of 1020 shedding episodes in 531 immunocompetent HSV-2-seropositive persons from whom daily swabs of genital secretions were collected.Results. Viral quantity varied by as much as a multiple of 10 million in a single person over time. Peak episode copy number was distributed approximately evenly from 10(3) through 10(8) HSV DNA copies/mL. Median rate of increase was 10(7.6) HSV DNA copies/day during the first 12 hours of an episode and 10(5) copies/d from episode initiation to peak. These values depended only moderately on episode duration. Median decay rate was -10(6.2) HSV DNA copies/d during the final 12 hours of an episode and -10(3.6) copies/d from peak to termination. Episodes lasted a median of 3 days (interquartile range, 1-8 days). Prolonged (> 5 days) episodes were associated with nonmonotonic decay.Conclusions. HSV-2 shedding episodes are notable for rapid expansion and decay and extreme heterogeneity of duration and viral production. The net effect of these dynamic episodes is frequent shedding at high copy numbers.
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  • Recurrence Rates of Genital Herpes

    Corey, Lawrence  

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