Episode Of Herpes Simplex Virus Research Articles

A Multicenter Assessment of the Outcomes and Toxicities of Foscarnet for Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex in Immunocompromised Patients.

Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized. This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance. Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction. Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.

Bilateral changes in corneal sensitivity after unilateral corneal infections

AbstractOcular infections such as herpes simplex virus (HSV) keratitis result in ocular sensitivity changes. During acute HSV episodes and eventually during postherpetic outbreaks, spontaneous pain and hyperalgesia are experienced, being reduced by treatment with Na+ channel blockers (not only by local anaesthetics but also by gabapentin, lacosamide or amitriptyline). At the same time, patients commonly develop hypoesthesia due to the decrease of sensitivity to mechanical stimulation, whose appearance could be due to the internalization of Na+ channels in trigeminal sensory neurons innervating the infected cornea.When explored using a gas esthesiometer that allows selective mechanical, chemical, heat and cold stimulation, HSV‐infected corneas showed those sensitivity disturbances to be expected when corneal polymodal nociceptor activity is altered. On the contrary, sensitivity to cold stimuli is not modified, which suggest that cold thermosensitive ocular neurons are not infected by the virus. A surprising result is the alteration, in the same sense although to a lesser degree, of the sensitivity of the contralateral eye. This contralateral altered sensitivity could be caused by a subclinical HSV infection of the contralateral side. Another possibility is that to be due to a neuroimmune interaction that ends up affecting the activity of sensory nerves of both eyes, in a similar way to what happens in non‐infectious inflammatory processes affecting only one eye.(PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103)

Karaciğer nakli alıcılarında herpes simpleks virüs viremisinin tanısı, klinik görünümleri ve tedavi yönetimi

Aim: We aimed to evaluate the clinical variations, possible risk factors and results of diagnostic procedures in liver transplant (LT) recipients who suffered from Herpes Simplex Virus (HSV) viremia in the post-transplant period, despite Cytomegalovirus (CMV) prophylaxis.
 Material and methods: The data of 1100 LT recipients were evaluated retrospectively. HSV DNA RT-PCR detected in blood and vesicular fluid samples of the patients with active painful mucocutaneous vesicular lesions and patients with organ involvement who had biopsy and confirmed HSV viremia were included in the study. The 110 recipients diagnosed with HSV viremia were included.
 Results: In 110 recipients, total 130 HSV viremia episodes were observed over sixty months. HSV viremia rate was 11.8%. Of the 130 HSV episodes, 120 (92.3%) were mucocutaneous form of the disease. In 10 cases, there was a specific organ involvement. HSV-1 was detected in all of viremia episodes. Sixty-four (49.2%) episodes developed six months after the LT, 41 (31.5%) episodes developed between the 1st and 6th months after LT, and 25 (20.3%) episodes were observed within the first postoperative month. All episodes were treated successfully with different antiviral therapy modalities.
 Conclusion: Despite CMV prophylaxis performed, HSV viremia may be occurred as a wide range of clinical presentation in LT recipients. It can be seen at any time point after the LT. HSV DNA RT-PCR from serum samples may not be sufficient for diagnosis of viremia, therefore the analysis of the vesicular fluid or the biopsy from the organs may be necessary for supporting the diagnosis.

P052 Using modern technology to improve the management of initial presentation of herpes simplex virus infection – communication with patients and delivering pcr results

IntroductionThe first presentation of Herpes Simplex Virus (HSV) may be distressing, with severe symptoms and associated stigma pertaining to the diagnosis. Initial audit confirmed clinic staff were inconsistent with how the initial clinical diagnosis was relayed to patients, the amount of information given and how follow up and PCR test results would be provided. Best practice dictates that detailed information and uncertainties around diagnosis should be communicated.MethodsStaff training was delivered using workshop style sessions and local protocol changed to highlight ‘10 key points’ to be communicated. An SMS used to deliver positive HSV PCR results was changed to include a bitlink to clinic website ‘Genital Herpes’ page and link to BASHH patient information leaflet. The automated results line was changed for PCR negative results, providing information for follow up if symptoms remained. A GP letter was created for PCR positives.ResultsAudit cycles were comparable in gender, age distribution, HSV type and PCR negativity rate. There was a significant improvement in the number of patients who received written information (p=0.0043), discussion on PCR sensitivity (p<0.0001), discussion on disclosure (p<0.0001) and significant reduction positive PCR results with no record of result being given (p=0.0091). There number of patients requiring follow up appointment for same episode of HSV did not change.DiscussionUsing modern technology can improve communication of important information to the patient and ensure the patient receives the result appropriately. Altering electronic resources can give more information and provide a back up when the diagnosis is unclear.

Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir

ABSTRACTPurpose: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN).Methods: Retrospective chart review.Results: Four immunocompetent men aged 45–90 years presented with ARN from 2008–2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2–8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40).Conclusions: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.

Long-term follow-up of HIV-infected patients once diagnosed with acyclovir-resistant herpes simplex virus infection

Acyclovir-resistant herpes simplex virus (HSV) infection is common in immunocompromised patients, but the course of such infection is little known. We describe the long-term follow-up of HIV-infected patients diagnosed once with acyclovir-resistant HSV infections. We retrospectively studied all HIV-infected patients between 2000 and 2010 diagnosed with virologically confirmed acyclovir-resistant HSV infection. Patients' socio-demographic and immunovirological characteristics were described. Response to foscarnet or cidofovir and recurrences were reported. Among 5295 HIV-infected patients, 13 (0.2%) were once diagnosed with an acyclovir-resistant HSV infection. Twelve patients were men, nine patients were of African origin. All patients reported previous acyclovir exposure and median CD4 count was 183 cells/mm(3) Ten patients presented exclusively with cutaneous lesions. Initially, 11 patients were treated with foscarnet and two with cidofovir. The median follow-up was 67 months (6-145). All patients recurred, 10 presenting at least one acyclovir-resistant HSV recurrence. The median number of acyclovir-resistant HSV recurrences per patient was 2 (0 - 5). Regarding the first and second recurrences, 7/13 (54%) and 5/11 (45%) HSV clinical isolates exhibited resistance to acyclovir, respectively. Acyclovir-resistant HSV infection prevalence was low in our cohort. The rate of acyclovir-resistant HSV episodes averaged 50% during the two first recurrences.

Rapidly Cleared Episodes of Oral and Anogenital Herpes Simplex Virus Shedding in HIV-Infected Adults

To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults. Twenty HSV-2-seropositive, HIV-seropositive adults, including 9 (45%) who were also HSV-1 seropositive, collected oral and anogenital swabs for HSV DNA polymerase chain reaction 4 times a day for 60 days. Samples were positive for HSV if we detected > or =150 copies of HSV DNA/mL of specimen. Median HSV shedding episode duration was 7.5 (range 4-253) hours for oral and 11 (range 4-328) hours for anogenital reactivation. Thirty-five percent of oral and 29% of anogenital reactivations lasted < or =6 hours, and 59% of oral and 53% of anogenital reactivations lasted < or =12 hours. Seven of 9 participants who shed orally and 10 of 15 who shed anogenitally had > or =1 reactivation lasting < or =6 hours. The median maximum level of HSV DNA detected in an episode increased with episode duration for both oral and anogenital episodes. Concurrent oral and anogenital shedding occurred more frequently than expected: oral HSV shedding was detected on 17% of time points with anogenital but 1% of time points without anogenital, shedding (P < 0.001). Rapidly cleared episodes of oral and anogenital HSV shedding occur in HIV-infected persons, supporting the hypothesis that frequent anogenital mucosal immune activation caused by HSV-2 is present in HIV coinfected persons, potentially contributing to HIV infectiousness.

An unusual vulval lesion in an HIV-infected woman

This is the case of a black African woman who presented with three distinct episodes of herpes simplex virus (HSV) infection unresponsive to first-line therapy. Clinical and virological resistance to aciclovir therapy was demonstrated, and although the first two episodes manifested as the deep ulceration often associated with HIV/HSV coinfection, the third was an atypical hypertrophic lesion. This is despite her CD4 count being persistently above 300 and there being no previous diagnosis of AIDS.

Epithelial Herpetic Simplex Keratitis Recurrence and Graft Survival After Corneal Transplantation in Patients With and Without Atopy

To compare the incidence of herpes simplex virus (HSV) epithelial recurrence and graft survival after penetrating keratoplasty (PK) in patients with and without self-reported atopy. Retrospective cohort comparative study. Cornea Service, Wills Eye Hospital. Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004 and who underwent primary PK for ocular HSV at the Cornea Service. From the 58 patients invited, 49 patients (50 eyes) were included. Nine patients were ineligible in accordance with the exclusion criteria: no active classic HSV episode before PK, immunosuppression, less than one year of follow-up, previous history of PK before presentation at the Service. Eligible patients filled out a questionnaire regarding their history of atopic disease, considering: presence of allergic rhinitis, asthma, or atopic dermatitis. Ocular history was obtained through chart review. main outcome measures: Incidence of epithelial HSV recurrences and corneal graft survival in both groups. Each group (atopic and nonatopic) included 25 eyes. The atopic patients had a mean incidence of 0.07 episode/eye year (SD +/- 0.9) compared with 0.12/eye year (standard deviation [SD] +/- 0.21) in the nonatopics (P = .002). At 10 years of follow-up, the survival rate in the atopics was of 92% and in the nonatopics was of 79% (P = .88). Nonatopics had significantly more epithelial recurrences after PK compared to atopics; however, both groups presented low incidences of recurrences and high graft survival rates.

Efficacy of Oral Antiviral Prophylaxis in Preventing Ocular Herpes Simplex Virus Recurrences in Patients With and Without Self-Reported Atopy

To compare the efficacy of oral antiviral prophylactic treatment for herpes simplex virus (HSV) recurrences in patients with and without self-reported atopy. Retrospective cohort comparative study. setting: Cornea Service, Wills Eye Hospital. study population: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004. From 244 patients invited, 54 patients (58 eyes) were included. One hundred and ninety patients were excluded according to exclusion criteria: no active episode during follow-up, immunosuppression, less than one year of follow-up, or previous history of penetrating keratoplasty. The Questionnaire regarding history of atopic disease, considers: presence of allergic rhinitis, asthma or atopic dermatitis, and chart review of ocular history. main outcome measures: Incidence of all types of HSV recurrences with and without antiviral prophylaxis within each group and between groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. Atopic/nonatopic (P value): mean follow-up without prophylaxis 8.1 (+/- 8.2)/7.3 years (+/- 8.6) (P = .71); mean follow-up with prophylaxis 2.9 (+/- 2.3)/2.6 years (+/- 2.2) (P = .51); the effect of prophylaxis significantly reduced the all recurrences in both groups except in the inflammatory recurrences in the atopic group and in the mixed recurrences in both groups. Prophylaxis decreased infectious episodes by 44% in nonatopic and 76% in atopics and decreased inflammatory manifestations by 69% in the nonatopic group and 8% in the atopic group. Antiviral prophylaxis for HSV recurrences was more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics.

Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy

To compare the characteristics of ocular herpes simplex virus (HSV) in patients with and without atopy. Retrospective cohort comparative study. Patients who presented at the Cornea Service, Wills Eye Hospital, between March 2003 and March 2004 who had been previously diagnosed in the same institution as having ocular HSV diagnosis or were just diagnosed as having the disease were asked to complete a study questionnaire that enabled categorization into atopic and nonatopic. In April 2005, 223 patients who agreed to be in the study had their charts reviewed, and 125 patients were excluded according to exclusion criteria: immunosuppression, follow-up less than one year, previous history of penetrating keratoplasty (PK) out of the Cornea Service, and no active HSV episode during follow-up. Incidence of all types of HSV recurrences. Bilaterality, visual loss, need for PK , and secondary bacterial infection in both groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. Ninety eight patients (110 eyes) were included in the study. Atopic/nonatopic (P value): the mean follow-up was 11.6 (+/- 10.6)/8.8 years (+/- 8.4) (P = .14); the mean incidence of HSV episodes per year of follow-up was: total episodes 0.32 (+/- 0.36)/0.28 (+/- 0.33) (P = .14), infectious 0.16 (+/- 0.22)/0.10 (+/- 0.14) (P < .01), inflammatory 0.11 (+/- 0.19)/0.11 (+/- 0.19) (P < .01), and mixed 0.09 (+/- 0.20)/0.07 (+/- 0.16) (P = .06); bilateral HSV was present in 9/3 patients (P = .22); the mean loss of vision was four lines of Snellen in both groups; PK was performed in 14 of 16 eyes (P = .45); secondary bacterial infection was present in two of four eyes (P = .26). Atopic patients had considerably more infectious and fewer inflammatory episodes when compared with nonatopics.

A Retrospective, Case-Control Study of Acyclovir Resistance in Herpes Simplex Virus

Occasional cases of acyclovir resistance have been documented in the treatment of herpes simplex virus (HSV) infection. Thirty-eight subjects with acyclovir-resistant infections were identified in an epidemiological surveillance program involving 1811 HSV-infected subjects in France. Twenty-three index cases from whom acyclovir-resistant HSV strains had been isolated were compared with 46 control subjects matched for immunological status. Sociodemographic characteristics, features of the acyclovir-resistant HSV episode, history of HSV infection, treatment, outcome, and immunological history were recorded. Twenty-two index case patients presented with immunodepression. Sixty-five percent reported clinically manifest recurrences, compared with 33% of matched control subjects. Significantly more index case patients had used antiviral drugs, and they had used them more often than had control subjects. However, 26.1% of index case patients reported no antiviral exposure in the previous 2 years. Two-thirds of the strains recovered from the index case patients were isolated because of suspicion of clinical resistance to acyclovir. Clinical treatment resistance is associated with acyclovir-resistant HSV strains, but acyclovir-resistant strains were also isolated from treatment-naive subjects.

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): A viral disease with an autoimmune component.

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.

Predictors of Recurrent Herpes Simplex Virus Keratitis

Determinants of the natural history of recurrent herpes simplex virus (HSV) keratitis have not been consistently established. We assessed how previous HSV eye disease affects the risk of recurrent HSV keratitis and evaluated whether demographic and other variables play any predictive role. Three hundred forty-six patients in the placebo group of the Herpetic Eye Disease Study's Acyclovir Prevention Trial who had experienced an episode of HSV eye disease in the previous year were followed up for 18 months. Recurrences were categorized according to the type of involvement. Relative rates of recurrence were compared for categories of demographic variables, types and number of previous ocular HSV episodes, previous nonocular HSV infection, and month of the year. Fifty-eight (18%) of the 346 patients developed epithelial keratitis and 59 (18%) developed stromal keratitis during the 18 months of follow-up. Previous epithelial keratitis did not significantly affect the risk of epithelial keratitis (p = 0.84). In contrast, previous stromal keratitis increased the risk of stromal keratitis 10-fold (p < 0.001), and the risk was strongly related to the number of previous episodes (p < 0.001). Age, gender, ethnicity, and nonocular herpes were not significantly associated with recurrences, and no seasonal effects were observed. Among patients who experienced active ocular HSV disease in the previous year, a history of epithelial keratitis was not a risk factor for recurrent epithelial keratitis. In contrast, previous, especially multiple, episodes of stromal keratitis markedly increased the probability of subsequent stromal keratitis.

The impact of the herpetic eye disease studies on the management of herpes simplex virus ocular infections.

Herpes simplex virus (HSV) is a leading cause of chronic infectious ocular disease in the United States. The morbidity from recurrent herpetic episodes is high, and the resultant corneal scarring may require penetrating keratoplasty for visual rehabilitation. Effective treatments for acute episodes of HSV have been verified by early Herpetic Eye Disease Study (HEDS) trials. The recent HEDS trial on the efficacy of oral acyclovir as prophylaxis against recurrent stromal keratitis represents the first report of a treatment likely to reduce long-term scarring from herpetic disease. This article reviews all the HEDS trials and the implications of their findings for the management of patients with ocular HSV.

Herpes simplex virus

Herpes simplex virus (HSV) infection is prevalent worldwide. Herpes labialis, caused predominantly by HSV-1, and herpes vulvovaginitis, caused predominantly by HSV-2, may result in significant morbidity and mortality for infected neonates exposed during delivery. The diagnosis of HSV infection is made by serological testing, viral culture, or polymerase chain reaction. Women with primary herpes vulvovaginitis exhibit a painful vesicular rash which is self-limited but may be followed by multiple recurrences. Women at greatest risk to transmit HSV to their neonates are those who experience their first episode of HSV during the latter stage of pregnancy. If infected, their neonates may have localized skin, eye and mucosal lesions, invasive central nervous system infection, or disseminated disease. Because of the potentially devastating outcome for a baby infected with HSV, pregnant women with active HSV lesions at delivery should be offered a cesarean section. Still, many neonates who are infected with HSV are born to women with asymptomatic HSV shedding. Therefore, prevention of HSV during pregnancy is exceedingly important.

The impact of active herpes simplex virus infection on human immunodeficiency virus load.

The effect of a concurrent herpes simplex virus (HSV) infection on human immunodeficiency virus type 1 (HIV-1) load was evaluated. Sixteen subjects were identified with an active HSV infection and had pre-outbreak, acute-phase, and post-outbreak plasma (n = 16) and peripheral blood mononuclear cell (PBMC) (n = 8) samples for evaluation. All subjects were treated for an acute HSV outbreak with acyclovir for 10 days, followed by chronic prophylaxis. HIV-1 plasma RNA levels were determined by branched DNA, and intracellular HIV gag mRNA copy numbers were determined by quantitative reverse transcriptase-polymerase chain reaction ELISA. Plasma virus load increased a median of 3.4-fold during the acute outbreak (range, 0- to 10-fold; P = .002), while post-outbreak levels (30-45 days after the appearance of lesions) remained above pre-outbreak, baseline levels in some subjects. Intracellular HIV gag mRNA increased during the outbreak as well. Thus, an acute HSV episode can result in increased HIV transcription and plasma virus load.

Are reported stress and coping style associated with frequent recurrence of genital herpes?

OBJECTIVES: This paper reports on the cross sectional data from the longitudinal study examining the impact of genital herpes simplex virus (HSV) infection on quality of life. In particular the...

Herpes simplex virus infection of the hand

The first episode of herpes simplex virus (HSV) infection of the hand can occur in association with infection at another site, such as primary HSV-1 gingivostomatitis. Autoinoculation is the likely route of transmission. The attacks are usually solitary and last about 14 days. A first episode that results from exogenous inoculation may be severely inflammatory and may last up to 28 days. The majority of cases are recurrent infections and most often occur in adults with HSV-2 infection.