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Find video protocols related to scientific articles indexed in Pubmed.
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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Oral HHV-8 replication among women in Mombasa, Kenya.
J. Med. Virol.
PUBLISHED: 03-11-2014
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Human herpesvirus-8 (HHV-8) replication in the oropharynx may play an important role in HHV-8 transmission and contribute to the development of Kaposi sarcoma (KS) in some individuals. Studies in the United States and Europe report high rates of HHV-8 DNA detection in saliva of HHV-8 infected men, but little is known about the natural history of HHV-8 among persons in sub-Saharan Africa, where prevalence of HHV-8 infection and KS is greatest. To address this gap, this study evaluated oral HHV-8 replication in a cohort of 40 HHV-8 seropositive Kenyan women. Study clinicians collected daily oral swabs from participants for up to 30 consecutive days, and swab samples were tested for HHV-8 DNA using quantitative, real-time polymerase chain reaction. HHV-8 was detected at least once in 27 (68%) participants, and the overall shedding rate was 23%. On days with HHV-8 detection, mean HHV-8 quantity was 4.5?log10 ?copies/ml. Among HIV-infected women, CD4 count ?500?cells/mm(3) versus <500?cells/mm(3) was associated with higher HHV-8 copy number (4.8?log10 ?copies/ml vs. 3.4?log10 ?copies/ml; coef 1.2 [95% CI, 0.5-1.9]; P?=?0.001) and a higher HHV-8 shedding rate (49% vs.12%; RR, 4.2 [95% CI, 0.8-21.4]; P?=?0.08). No other factors were associated with HHV-8 shedding rate or copy number. The study demonstrates high rates and quantity of HHV-8 in the oropharynx of HHV-8 seropositive African women. These findings support the observation that oral replication is an essential feature of HHV-8 infection, with likely implications for HHV-8 transmission and KS pathogenesis.
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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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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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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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Longitudinal study on oral shedding of herpes simplex virus 1 and varicella-zoster virus in individuals infected with HIV.
J. Med. Virol.
PUBLISHED: 04-04-2013
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Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n?=?715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain.
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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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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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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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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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Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 03-23-2011
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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.
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Genital HSV detection among HIV-1-infected pregnant women in labor.
Infect Dis Obstet Gynecol
PUBLISHED: 01-13-2011
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To compare genital HSV shedding among HIV-positive and HIV-negative women.
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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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Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-18-2010
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Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8(+) lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8(+) lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8(+) T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8(+) lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host.
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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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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 detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men.
PLoS ONE
PUBLISHED: 02-04-2010
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The association between baseline seropositivity to human adenovirus (HAdV) type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection.
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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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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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Impact of HIV infection and Kaposi sarcoma on human herpesvirus-8 mucosal replication and dissemination in Uganda.
PLoS ONE
PUBLISHED: 01-20-2009
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Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.
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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.

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

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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.