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Find video protocols related to scientific articles indexed in Pubmed.
Respiratory syncytial virus transplacental antibody transfer and kinetics in mother-infant pairs in bangladesh.
J. Infect. Dis.
PUBLISHED: 06-05-2014
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Pneumonia is the leading cause of childhood mortality globally. Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia. Maternal serum antibody protects infants from RSV disease. The objective of our study was to characterize RSV antibody levels in mother-infant pairs.
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Clinical utility of droplet digital PCR for human cytomegalovirus.
J. Clin. Microbiol.
PUBLISHED: 05-28-2014
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Human cytomegalovirus (CMV) has historically been the major infectious cause of morbidity and mortality among patients receiving hematopoietic cell or organ transplant. Standard care in a transplant setting involves frequent monitoring of CMV viral load over weeks to months to determine when antiviral treatment may be required. Quantitative PCR (qPCR) is the standard molecular diagnostic method for monitoring. Recently, digital PCR (dPCR) has shown promise in viral diagnostics, although current dPCR systems have lower throughput than qPCR systems. Here, we compare qPCR and droplet digital PCR (ddPCR) for CMV detection in patient plasma samples. Droplet digital PCR exhibits increased precision over qPCR at viral loads of ?4 log10 with equivalent sensitivity. However, retrospective analysis of longitudinal samples from transplant patients with CMV viral loads near therapeutic thresholds did not provide evidence that the improved precision of ddPCR would be of clinical benefit. Given the throughput advantages of current qPCR systems, a widespread switch to dPCR for CMV monitoring would appear premature.
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Three phase III randomized controlled trials of topical resiquimod 0.01-percent gel to reduce anogenital herpes recurrences.
Antimicrob. Agents Chemother.
PUBLISHED: 04-07-2014
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Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ?4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.
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Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR.
Clin. Chem.
PUBLISHED: 03-04-2014
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Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests.
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Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy.
J. Clin. Virol.
PUBLISHED: 02-21-2014
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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.
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Virologic and immunologic evidence of multifocal genital herpes simplex virus 2 infection.
J. Virol.
PUBLISHED: 02-19-2014
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Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.
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In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease.
Mol Ther Nucleic Acids
PUBLISHED: 02-06-2014
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Following acute infection, herpes simplex virus (HSV) establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they do not prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks in latent HSV genomes by rare-cutting endonucleases, leading to mutagenesis of essential viral genes. We tested this approach in an in vitro HSV latency model using the engineered homing endonuclease (HE) HSV1m5, which recognizes a sequence in the HSV-1 gene UL19, encoding the virion protein VP5. Coexpression of the 3'-exonuclease Trex2 with HEs increased HE-mediated mutagenesis frequencies up to sixfold. Following HSV1m5/Trex2 delivery with adeno-associated viral (AAV) vectors, the target site was mutated in latent HSV genomes with no detectable cell toxicity. Importantly, HSV production by latently infected cells after reactivation was decreased after HSV1m5/Trex2 exposure. Exposure to histone deacetylase inhibitors prior to HSV1m5/Trex2 treatment increased mutagenesis frequencies of latent HSV genomes another two- to fivefold, suggesting that chromatin modification may be a useful adjunct to gene-targeting approaches. These results support the continuing development of HEs and other nucleases (ZFNs, TALENs, CRISPRs) for cure of chronic viral infections.Molecular Therapy-Nucleic Acids (2014) 3, e1; doi:10.1038/mtna.2013.75; published online 4 February 2014.
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Frequent genital HSV-2 shedding among women during labor in Soweto, South Africa.
Infect Dis Obstet Gynecol
PUBLISHED: 01-21-2014
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Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor.
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Helicase-primase inhibitor pritelivir for HSV-2 infection.
N. Engl. J. Med.
PUBLISHED: 01-17-2014
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Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection.
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Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.
J. Infect. Dis.
PUBLISHED: 07-30-2013
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Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.
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Quantitation of cytomegalovirus DNA load in dried blood spots correlates well with plasma viral load.
J. Clin. Microbiol.
PUBLISHED: 05-15-2013
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An assay to accurately quantitate cytomegalovirus (CMV) load in finger-stick-collected dried blood spots (DBS) could potentially be useful for field studies or for analyzing patient self-collected specimens. We therefore assessed CMV DNA load in paired venipuncture-collected plasma samples and finger-stick DBS, using a previously validated quantitative PCR assay. Assay variability, sensitivity, and changes in viral load during antiviral therapy in finger-stick DBS were compared to the reference plasma quantitative PCR assay, using 106 prospectively collected pairs of finger-stick DBS and plasma samples from 35 solid-organ transplant (SOT) patients. The DBS assay showed good agreement with the reference plasma viral load assay on the log10 scale (Pearson correlation coefficient, 0.92; P < 0.001). The 95% limit of detection of the DBS assay was estimated at 2,700 plasma copies/ml (675 plasma IU/ml). In 94% (76/81) of paired DBS and plasma samples above the limit of detection, the difference in CMV load was <1 log10. CMV viral load changes during antiviral treatment were comparable in plasma and DBS. We conclude that finger-stick DBS provides a convenient sample type for quantitation of CMV load that correlates well with plasma levels. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted.
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An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia.
J. Clin. Virol.
PUBLISHED: 04-24-2013
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Additional drugs are needed for the treatment of cytomegalovirus (CMV) infection. Artesunate is an antimalarial drug that has activity against CMV in vitro and in a rodent model. Only a small number of case reports are available describing the clinical effects of artesunate on CMV infection, and these yielded inconsistent results.
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Impact of human cytomegalovirus (CMV) infection on immune response to pandemic 2009 H1N1 influenza vaccine in healthy adults.
J. Med. Virol.
PUBLISHED: 04-04-2013
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Human cytomegalovirus (CMV) infection has been implicated in immunosenescence. To examine the influence of CMV on ability of healthy adults to respond to a novel influenza antigen, the rate of seroconversion and the magnitude of titers to pandemic 2009 H1N1 vaccine was assessed. The clinical trial was stratified by age; 52 persons aged 18-64 and 55 aged 65 and older were enrolled. Among the younger group, 33% had CMV antibody compared with 62% among the older group. No differences by CMV seropositivity in the proportion of participants achieving a seroprotective titer 21 days following the second immunization were noted. However, the geometric mean titer in hemagglutination inhibition assay was significantly higher among CMV seronegative younger participants compared with CMV seropositive younger participants (385 vs. 142, P?=?0.013). In contrast, among the older group, CMV serostatus was not associated with differential antibody titers (53 vs. 63, P?=?0.75). These data suggest that CMV may shape immune response to neoantigens among younger persons; these groups should be included in future studies of immunosenescence and CMV.
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High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-02-2013
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Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding.
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Molecular epidemiology of respiratory syncytial virus transmission in childcare.
J. Clin. Virol.
PUBLISHED: 01-10-2013
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Respiratory syncytial virus (RSV) is the most important cause of serious respiratory infections in young children. No prior studies using molecular techniques to examine RSV transmission in the community childcare setting have been performed.
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Mycobacterium tuberculosis bacteremia in a cohort of HIV-infected patients hospitalized with severe sepsis in Uganda-high frequency, low clinical sand derivation of a clinical prediction score.
PLoS ONE
PUBLISHED: 01-01-2013
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When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.
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Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract.
Elife
PUBLISHED: 01-01-2013
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Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium. DOI:http://dx.doi.org/10.7554/eLife.00288.001.
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Sample Size for a Binomial Proportion with Autocorrelation.
Stat Commun Infect Dis
PUBLISHED: 10-24-2011
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A flexible sample size computation is desired for a binomial outcome consisting of repeated binary measures with autocorrelation over time. This type of outcome is common in viral shedding studies, in which each individuals outcome is a proportion: the number of samples on which virus is detected out of number of samples assessed. Autocorrelation between proximal samples occurs in some conditions such as herpes infection, in which reactivation is episodic. We determine a sample size computation that accounts for: (1) participant-level differences in outcome frequency, (2) autocorrelation in time between samples, and (3) varying number of samples per participant. In addition, we develop a computation appropriate for crossover designs that accounts for the dependence of the investigational treatment effect on the pretreatment detection frequency. The computations are validated through comparison with real and simulated data, and sensitivity to misspecification of parameter values is examined graphically.
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Detailed analysis of mucosal herpes simplex virus-2 replication kinetics with and without antiviral therapy.
J. Antimicrob. Chemother.
PUBLISHED: 08-24-2011
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The presence of herpes simplex virus-2 (HSV-2) shedding episodes correlates with transmission to sexual partners and neonates, and some episodes correlate with disease manifestations. HSV-2-targeted guanosine analogues are effective when given on a prophylactic basis, but do not completely eliminate recurrences, asymptomatic shedding or transmission. We sought to describe the impact of twice-daily aciclovir and famciclovir on shedding episodes.
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Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men.
J. Med. Virol.
PUBLISHED: 08-13-2011
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Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually infected men enrolled in three previous clinical trials of valacyclovir and famciclovir for HIV-1 and/or HSV-2 suppression. Fifty-eight participants contributed 6,036 swabs. HHV-8 was detected in 1,128 (19%) of 6,036 swabs, including 618 (21%) of 2,992 on placebo, 323 (15%) of 2,221 on valacyclovir, and 187 (23%) of 823 on famciclovir. After adjusting for baseline HIV viral load and highly active antiretroviral therapy (HAART) use, an 18% reduction in HHV-8 shedding frequency (IRR 0.822; P?=?0.011) was found in participants on valacyclovir and a 30% reduction (IRR 0.700; P?
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The kinetics of mucosal herpes simplex virus-2 infection in humans: evidence for rapid viral-host interactions.
J. Infect. Dis.
PUBLISHED: 07-28-2011
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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.
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Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: a case-control study.
AIDS
PUBLISHED: 05-07-2011
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adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition.
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Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection.
J. Clin. Microbiol.
PUBLISHED: 05-04-2011
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Propionibacterium acnes is increasingly recognized as an important agent of prosthetic joint infection (PJI). However, the optimum culture conditions for recovery of this organism from PJI specimens have not been determined. By applying a prolonged 28-day culture incubation to all periprosthetic specimens received for bacterial culture from 198 revision arthroplasty procedures, we retrospectively determined that a 13-day culture incubation period is necessary for the recovery of P. acnes from patients with PJI. Incubation beyond this period was associated with increasing recovery of nondiagnostic isolates: 21.7% of P. acnes isolates believed to be clinically unimportant were recovered after 13 days of incubation. Importantly, a diagnosis of P. acnes PJI would have been missed in 29.4% of patients had extended culture incubation been applied only to anaerobic culture media. Although specimens from P. acnes PJIs were more commonly associated with the presence of ? 2 culture media positive for growth, acute inflammation (? 5 neutrophils/high-power field) was observed in only 40% of patients with PJIs that had more than one specimen submitted for bacterial culture. These results support the need for a minimum culture incubation period of 13 days to be applied to both aerobic and anaerobic culture media for all periprosthetic specimens. Optimal recovery of infecting organisms from PJI specimens will be an important component in generating a universal definition for PJI due to indolent agents of infection, such as P. acnes.
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Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection.
JAMA
PUBLISHED: 04-14-2011
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Since herpes simplex virus type 2 (HSV-2) antibody tests have become commercially available, an increasing number of persons have learned that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain.
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Risk Factors for HSV-2 Infection among Sexual Partners of HSV-2/HIV-1 Co-Infected Persons.
BMC Res Notes
PUBLISHED: 03-01-2011
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Herpes simplex virus type 2 (HSV-2) is the most frequent cause of genital ulcer disease worldwide and has been associated with increased risk for HIV-1 acquisition and transmission. We conducted a cross-sectional analysis of risk factors for HSV-2 infection among HIV-1 uninfected partners, whose partners were co-infected with HIV-1 and HSV-2.
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Predictors of survival after a diagnosis of non-Hodgkin lymphoma in a resource-limited setting: a retrospective study on the impact of HIV infection and its treatment.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-26-2011
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We examined factors associated with survival among patients with newly diagnosed non-Hodgkin lymphoma (NHL) in Uganda.
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Development of an interferon-gamma ELISPOT assay to detect human T cell responses to HSV-2.
Vaccine
PUBLISHED: 01-11-2011
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The need for an HSV-2 vaccine is great considering the increasing prevalence of HSV-2 despite the widespread use of antiviral drugs. Human clinical trials of HSV-2 vaccines that elicit neutralizing antibodies have proven to be only partially effective suggesting that induction of effective T cell responses to HSV-2 is also a critical component to an efficacious vaccine. A sensitive and specific assay to measure HSV-specific T cell responses is a necessary part of vaccine development and thus we undertook the development of an interferon-? (IFN-?) ELISPOT assay to measure T cell responses to HSV-2.
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The effects of daily distress and personality on genital HSV shedding and lesions in a randomized, double-blind, placebo-controlled, crossover trial of acyclovir in HSV-2 seropositive women.
Brain Behav. Immun.
PUBLISHED: 01-07-2011
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Herpes simplex virus (HSV) infections are ubiquitous in humans, but the determinants of clinical and virologic severity are not completely understood. Prior research has suggested that psychological distress can be a co-factor in reactivation of latent HSV infection. Personality traits such as extraversion and neuroticism influence stress attributions and may inform the relationship between psychological distress and health outcomes. Earlier studies in this area have primarily focused on subjective reports of HSV lesion recurrence, but such reports may be influenced by both personality traits and distress. We report results from a randomized, double-blind, placebo-controlled, crossover trial of acyclovir in 19 women for whom personality was assessed at baseline and daily assessments of genital lesions, stress, anxiety, and depression levels were collected for 22 weeks. In addition, daily swabs of the genital mucosa were collected to assess HSV-2 viral reactivation. We found that daily stress predicted genital lesion frequency, and that daily stress, anxiety, and depression predicted genital lesion onset approximately 5 days before onset. Anxiety was also associated with genital lesions 3 days after onset. Distress and viral reactivation were not associated; and no personality traits were associated with any of the outcomes. These results support the hypothesis that psychological distress is both a cause and a consequence of genital lesion episodes.
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Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.
J. Infect. Dis.
PUBLISHED: 12-09-2010
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Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking.
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Rapidly cleared episodes of oral and anogenital herpes simplex virus shedding in HIV-infected adults.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-10-2010
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To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults.
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Diversity in CD8(+) T cell function and epitope breadth among persons with genital herpes.
J. Clin. Immunol.
PUBLISHED: 05-27-2010
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CD8(+) T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8(+) T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8(+) T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8(+) T cell epitopes. CD8(+) T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.
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Rapid polymerase chain reaction assay to detect herpes simplex virus in the genital tract of women in labor.
Obstet Gynecol
PUBLISHED: 05-27-2010
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To develop a rapid quantitative real-time polymerase chain reaction (PCR) to detect herpes simplex virus (HSV) in the genital secretions of women that may be used in labor.
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Frequent and prolonged shedding of bocavirus in young children attending daycare.
J. Infect. Dis.
PUBLISHED: 04-27-2010
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Little is known about human bocavirus (HBoV) persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms.
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APOE genotype is associated with oral herpetic lesions but not genital or oral herpes simplex virus shedding.
Sex Transm Infect
PUBLISHED: 04-21-2010
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Apolipoprotein E is polymorphic in the human population. APOE4 has previously been reported to correlate with symptomatic oral and genital herpes disease.
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Detailed characterization of T cell responses to herpes simplex virus-2 in immune seronegative persons.
J. Immunol.
PUBLISHED: 02-17-2010
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In 2003, we described a small cohort of subjects (n = 6) who possessed no detectable serum Abs to HSV-1 or HSV-2 and no clinical or virological evidence of mucosal HSV infection yet possessed consistently detectable HSV-specific T cell responses measured primarily by lymphoproliferative (LP) and CTL assays to whole HSV-2 Ag. We termed these persons immune seronegative (IS). This report characterizes the T cell responses in 22 IS subjects largely recruited from studies of HSV-seronegative subjects in ongoing sexual relationships with HSV-2-seropositive (HSV-2(+)) partners using pools of overlapping peptides spanning 16 immuno-prevalent HSV-2 proteins. Overall, 77% of IS subjects had HSV-specific LP responses, 85% had IFN-gamma ELISPOT responses to at least one HSV-2 peptide pool, and 55% had both LP and IFN-gamma ELISPOT responses. In some cases, IFN-gamma ELISPOT responses were in excess of 500 spot-forming cells per 10(6) PBMCs and persisted for over 5 y. Although HSV-2(+) subjects (n = 40) had frequent responses to glycoproteins and tegument and immediate-early (IE) proteins of HSV-2, T cell responses in IS subjects were directed primarily at UL39 and the IE proteins ICP4 and ICP0. These data suggest that the antigenic repertoire of T cells in IS subjects is skewed compared with that of HSV-2(+) subjects and that IS subjects had more frequent T cell responses to IE proteins and infrequent T cell responses to virion components. Understanding the mechanism(s) by which such responses are elicited may provide important insights in developing novel strategies for preventing acquisition of sexually acquired HSV-2.
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Overlapping reactivations of herpes simplex virus type 2 in the genital and perianal mucosa.
J. Infect. Dis.
PUBLISHED: 01-22-2010
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Genital shedding of herpes simplex virus (HSV) type 2 occurs frequently. Anatomic patterns of genital HSV-2 reactivation have not been intensively studied.
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Detection of bocavirus in saliva of children with and without respiratory illness.
J. Clin. Microbiol.
PUBLISHED: 09-30-2009
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We evaluated saliva samples from 149 children 2 to 11 years old for human bocavirus (hBoV) DNA. hBoV was detected in saliva samples at asymptomatic enrollment in 3% (5/149) and during respiratory illness in 2% (2/106) of the cases. hBoV was detected in only 1/149 asymptomatic and 0/106 illness nasal samples.
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Frequent release of low amounts of herpes simplex virus from neurons: results of a mathematical model.
Sci Transl Med
PUBLISHED: 08-19-2009
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Herpes simplex virus-2 (HSV-2) is a sexually transmitted infection that is the leading cause of genital ulcers worldwide. Infection is life long and is characterized by repeated asymptomatic and symptomatic shedding episodes of virus that are initiated when virus is released from neurons into the genital tract. The pattern of HSV-2 release from neurons into the genital tract is poorly understood. We fit a mathematical model of HSV-2 pathogenesis to curves generated from daily quantification of HSV in mucosal swabs performed from patients with herpetic genital ulcers. We used virologic parameters derived from model fitting for stochastic model simulations. These simulations reproduced previously documented estimates for shedding frequency, and herpetic lesion diameter and frequency. The most realistic model output occurred when we assumed minimal amounts of daily neuronal virus introduction. In our simulations, small changes in average total quantity of HSV-2 released from neurons influenced detectable shedding frequency, while changes in frequency of neuronal HSV-2 release had little effect. Frequent HSV-2 shedding episodes in humans are explained by nearly constant release of small numbers of viruses from neurons that terminate in the genital tract.
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A pooled analysis of the effect of condoms in preventing HSV-2 acquisition.
Arch. Intern. Med.
PUBLISHED: 07-15-2009
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The degree of effectiveness of condom use in preventing the transmission of herpes simplex virus 2 (HSV-2) is uncertain. To address this issue, we performed a large pooled analysis.
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HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.
AIDS
PUBLISHED: 01-27-2009
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Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels.
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Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.
PLoS ONE
PUBLISHED: 01-13-2009
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The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.
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Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition.
Nat. Med.
PUBLISHED: 01-07-2009
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To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy. The CD4(+) T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies. The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition.
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Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: results of analyses from a multicenter randomized trial.
BMC Infect. Dis.
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The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries.
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Peripheral blood CD4 T-cell and plasmacytoid dendritic cell (pDC) reactivity to herpes simplex virus 2 and pDC number do not correlate with the clinical or virologic severity of recurrent genital herpes.
J. Virol.
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Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals.
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Case-crossover analysis of condom use and herpes simplex virus type 2 acquisition.
Sex Transm Dis
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Although growing evidence suggests that condoms offer moderate protection against herpes simplex virus type 2 (HSV-2), inability to control for unknown or unmeasured confounders associated with sexual activity may reduce the accuracy of the estimates. The case-crossover design offers increased control of individual-level confounders, and was thus used with the aim of producing a more accurate estimate of the effect of condom use on HSV-2 acquisition.
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Determinants of per-coital-act HIV-1 infectivity among African HIV-1-serodiscordant couples.
J. Infect. Dis.
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Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 (HIV-1) is important for designing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1.
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Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials.
Lancet
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Skin and mucosal herpes simplex virus type 2 (HSV-2) shedding predominantly occurs in short subclinical episodes. We assessed whether standard-dose or high-dose antiviral therapy reduces the frequency of such shedding.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.