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Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy.

Herpes viruses are characterized by their ability to establish and maintain latent infections that can be reactivated. Several stimuli can trigger the reactivation of herpes viruses, which are perhaps best recognized in the recurrent blisters and ulcers associated with herpes simplex virus. We present two clinical cases of reactivation of herpes simplex virus during radiation therapy for management of cancers of the head and neck. Although the role of ionizing radiation in the reactivation of herpes simplex virus has not been established, we review the viral and host events associated with the establishment of orofacial herpes simplex virus infection, latency, and reactivation of the virus. We discuss current models of viral reactivation and suggest directions for further clinical research into the reactivation of orolabial herpes simplex virus during radiotherapy.

Acyclovir↗

Autoinoculation herpes of the hand in a child with recurrent herpes labialis.

Herpes simplex virus infections involving the fingers and hands have been reported primarily in medical and dental personnel. A 10-year-old boy is described who presented with herpes simplex virus infection of his left hand two weeks after resolution of an episode of recurrent herpes labialis. Since herpes simplex infections of the fingers and hands may be confused with a variety of other more common conditions, clinicians should be alert to this possibility when diagnosing vesiculopustular lesions of the hands, particularly in medical and dental personnel and in patients with histories of recurrent herpes simplex infections elsewhere. A need for greater patient awareness of the potential for herpes simplex virus autoinoculation is also stressed.

Child↗

Herpes zoster and zosteriform herpes simplex virus infections in immunocompetent adults.

Among 111 immunocompetent patients referred to a general hospital setting with the clinical diagnosis of herpes zoster, viral cultures were obtained from 47 patients. Six of these patients (13 percent) had herpes simplex virus isolated, with four of the six infections involving the facial distribution, and the other two involving the T4 (breast) distribution. Excluding those in whom herpes simplex virus was isolated, the mean age (+/- SD) of the remaining 105 patients was 50 +/- 19 years. Thirty-two percent of the patients were at least 65 years old; however, 39 percent were younger than 40 years of age. Thus, herpes zoster frequently occurs in young, immunocompetent adults. Also, since zosteriform rashes may be caused by herpes simplex virus, viral cultures of lesions are useful to differentiate infections caused by herpes simplex virus from those due to varicella-zoster virus. The need to distinguish between these two viruses may be important with the advent of antiviral drugs and for use of the proper epidemiologic isolation procedures.

Adolescent↗

Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis.

The objectives of this study were to evaluate the reliability of herpes simplex virus (HSV) PCR testing in cerebrospinal fluid (CSF) for the detection of herpes simplex encephalitis. This was done by examining retrospectively the clinical follow-up of a large group of patients tested routinely by HSV-PCR. In addition, an attempt was made to assess the incidence of herpes simplex encephalitis in a central European population. CSF samples from 1,427 patients from all Vienna hospitals were submitted for HSV-PCR testing during a period of 4 years and 8 months. Herpes simplex encephalitis was detected by PCR in 12 cases and by serological methods in one additional patient. Retrospective analysis of the course of disease, which was possible in 799 PCR-negative patients, led to the identification of three additional cases in which herpes simplex encephalitis appears to have occurred despite negative PCR results. Failure of the PCR in these patients is most likely due to the time of obtaining CSF during the course of disease. A high specificity of the assay was demonstrated by the lack of false positive results in any of the 708 cases in which other causes for the neurological symptoms had been identified in the follow-up. The incidence of herpes simplex encephalitis in the population of Vienna was between 1 case/469,000-577,000 individuals/year. The highest annual incidence was detected in the age group between 3 months and 3 years, which, however, could not be confirmed statistically.

Adolescent↗

Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 1: herpes simplex virus infections.

Primary herpes simplex virus (HSV) infection may lead to severe illness in pregnancy and may be associated with transplacental virus transmission and fetal infection. The consequences may be abortion, stillbirth and congenital malformations. In neonates, the clinical findings after intrauterine HSV infection are characterized by skin lesions, diseases of the eye and neurologic damage. Herpes genitalis of pregnant women at the time of labor may result in life-threatening neonatal herpes. Currently, neither active nor passive immunization is available to prevent HSV infections during pregnancy and in the newborn infant. Therefore, antiviral treatment using aciclovir and/or valaciclovir must be considered in all primary episodes of genital herpes as well as in neonates who show signs of either infection. Clinical herpes lesions of the genitalia and/or positive test for virus detection at the time of delivery are an indication for cesarean section. However, this surgical intervention may be reduced by suppressive treatment of recurrent genital herpes with aciclovir or valaciclovir.

Acyclovir↗

Prevalence of herpes simplex type 2 antibodies and a clinical history of herpes in three different populations in Campinas City, Brazil.

OBJECTIVES: To determine the seroprevalence of herpes simplex virus type 2 (HSV-2) antibodies and the relation between the history of clinical herpes and the presence of type-specific HSV-2 antibodies in three different populations from the city of Campinas City, Brazil. POPULATION AND METHODS: One hundred and one college students, 96 patients with sexually transmitted diseases (STD), and 102 women at delivery were interviewed and blood samples were collected. Total HSV (HSV-1 and HSV-2) antibodies were screened by enzyme-linked immunosorbent assay (ELISA) and type-specific HSV-2 antibodies were detected by Western blot assay. RESULTS: Herpes simplex virus antibodies were detected in 66.3% of the students, 97.1% of the women at delivery, and 99.0% of the STD patients. Type-specific HSV-2 antibodies were detected in 6.9% of the students, 22.6% of the women at delivery, and in 53.1% of the STD patients. History of genital herpes was reported by none of the students, by one of the women at delivery, and by 11 of 51 (21.6%) STD patients who were HSV-2 seropositive. Four of the 45 (8.9%) seronegative STD patients reported a history of genital herpes. CONCLUSION: The prevalence of HSV-2 infection in Campinas City can be significantly affected by the characteristics of the population studied, as was shown in previous studies. The sensitivity of the history of genital herpes was low in the present series, stressing that prophylactic measures for vertical and horizontal transmission of HSV-2 should not be based only on a positive history of genital ulcers.

Adolescent↗

Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students.

UNLABELLED: A retrospective review of genital herpes simplex virus (HSV) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993. BACKGROUND: Herpes simplex virus (HSV) type 1 is usually thought to cause less than 30% of genital herpes infections in the United States, but the proportion of infections resulting from HSV-1 is increasing in some populations. GOAL: The goal was to review the relative proportion of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of U.S. college students and to assess trends in the change of this proportion over time. STUDY DESIGN: Genital HSV isolates collected at a university student health service from 1993 to 2001 (n = 499) were reviewed retrospectively. Analyses included comparisons of isolates by HSV type, age group, and sex. RESULTS: The proportion of newly diagnosed genital herpes infections resulting from HSV-1 increased from 31% in 1993 to 78% in 2001 (P <0.001, linear trend P <0.001). HSV-1 was more common in females than males, but increases were noted for both sexes. HSV-1 was more common in persons aged 16 to 21 than in persons aged 22 or older. CONCLUSIONS: HSV-1 has become the most common cause of newly diagnosed genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio.

Adolescent↗

Herpes simplex virus infections of the central nervous system. Encephalitis and neonatal herpes.

Herpes simplex virus (HSV) infections are among the most commonly encountered in humans. Fortunately, the resulting diseases are more usually nuisances, such as recurrent fever blisters, rather than life threatening or morbidity inducing. Nevertheless, HSV can result in disease of the central nervous system (CNS) with attendant neurological complications. Examples of the latter include herpes simplex encephalitis (HSE) or neonatal HSV infection. The past decade has witnessed significant advances in our understanding of the pathogenesis of these 2 forms of disease and, even more importantly, their amenability to treatment. This review summarises our current understanding of the natural history, pathogenesis, presentation, and treatment of HSV infections of the CNS. Because of the life-threatening nature of herpes simplex infections of the CNS, particular attention is paid to clinical presentation and differential diagnosis of confounding entities which mimic herpes simplex encephalitis. The controversy of brain biopsy versus alternative noninvasive diagnostic procedures is discussed. Clinical presentation and, importantly, the lack of uniform clinical presentation, as well as the value of intervention with appropriate antiviral drugs such as aciclovir and vidarabine (adenine arabinoside, ara-A), are stressed. The clinical outcome of herpes simplex virus infections of the CNS with therapy is particularly relevant. In spite of early intervention with selective and specific inhibitors of viral replication, return to normal function is not always achieved. At the conclusion of this review, the reader should be aware of the potential value of therapy as well as the problems encountered with diagnosis and management of patients with herpes simplex virus infections of the CNS.

Encephalitis↗

Interventions for herpes simplex virus epithelial keratitis.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of antiviral pharmacology and of herpes simplex virus eye disease have evaluated different commercially available agents, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis. SEARCH STRATEGY: Sources searched for relevant studies were the Cochrane Eyes and Vision Group specialized register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE, Index Medicus, Excerpta Medica Ophthalmology, reference lists of primary reports, review articles, and corneal textbooks and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review includes comparative clinical trials that assessed oral or topical ophthalmic antiviral agents, or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment. MAIN RESULTS: This review includes data from 96 trials which randomised a total of 4991 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical and physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, and was useful with debridement. REVIEWER'S CONCLUSIONS: Currently available and investigational antiviral agents are effective and nearly equivalent, but the combination of an antiviral nucleoside and interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome and should consider the effect of lesion size and other characteristics on treatment response.

Administration, Oral↗

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars.

BACKGROUND: Cutaneous lymphoid infiltrates at sites of herpes zoster scars in patients with B-cell chronic lymphocytic leukemia (B-CLL) often are diagnosed as benign lymphoid hyperplasia ("pseudolymphomas"). The histologic and immunophenotypic features of these lesions are not well characterized. Appearance of skin lesions in B-CLL patients is considered a poor prognostic sign. METHOD: Eight punch biopsies from five patients (three males, two females; mean age, 66.7 years) affected by B-CLL and presenting with lesions at sites of previous herpes simplex (upper lip, one patient) or herpes zoster (trunk, four patients; forehead, one patient) infections were included in the study. Histologic examination was performed on routine sections stained with hematoxylin and eosin and Giemsa. Immunohistologic stainings were performed with a standard three-step immunoperoxidase technique on formalin fixed, paraffin embedded tissue sections. RESULTS: Specific cutaneous infiltrates of B-CLL were diagnosed histopathologically and immunophenotypically in eight biopsies from all five patients. Clinically, patients presented with erythematous papules or plaques confined to the area of previous herpes virus eruptions. Histopathologic features in most cases were characterized by a variably dense perivascular and periadnexal infiltrate of small hyperchromatic lymphocytes throughout the entire dermis, reaching the subcutaneous fat. In one case, a dense, diffuse infiltrate involving the entire dermis was observed. A granulomatous reaction with presence of epithelioid and multinucleated giant cells was a prominent feature in four biopsies from three patients. Light areas containing large lymphoid cells with features of prolymphocytes and paraimmunoblasts (so-called "proliferation centers") could be observed only in the case characterized by a diffuse infiltrate. Immunohistology revealed an aberrant CD20+/CD43+ phenotype of neoplastic B cells, which is not found in normal B lymphocytes (CD20+/CD43-). Reactive T lymphocytes were present in all lesions and had a normal CD20-/CD43+/CD45Ro+ phenotype. At the time of this writing, four patients were alive without signs of skin disease after a mean follow-up of 58.5 months, and one patient died of B-CLL 24 months after the cutaneous eruption. CONCLUSIONS: Specific cutaneous infiltrates of B-CLL are not uncommon at sites of herpes virus scars. The diagnosis can be confirmed by histopathologic and immunophenotypic criteria. The prognosis is better than previously reported.

Aged↗

[Therapy of recurrent herpes simplex and its surveillance by MIF determination: with levamisole, BCG, urushiol and herpes antigen vaccine (author's transl)].

Thirty patients with recurrent herpes simplex and 6 controls were included in our study. Before initiation of treatment, during therapy with Levamisole, BCG, poison ivy and herpes antigen vaccine and, thereafter, MIF-determinations were performed. The latter test proved to be a useful parameter in evaluating the sensitivity against herpes infection, (and subsequent recurrent manifestations), and effect of therapy. Treatment with Levamisole, BCG and herpes antigen vaccine was successful. MIF-inhibition values paralleled the therapeutic effect in the Levamisole- and herpes antigen vaccine treated group, not however, in the BCG-treated patients

Antigens, Viral↗

The relative infrequency and low levels of neutralising and immunoprecipitating antibody to herpes simplex viruses types 1 and 2 in patients with a history of recurrent herpes genitalis.

Twenty-seven per cent of 70 patients with a history of recurrent herpes genitalis but no concomitant history of recurrent oral or peri-genital disease, had no detectable neutralising antibody against type 1 or type 2 herpes simplex virus; the prevalence and levels of neutralising antibody were similar to 53 patients with no history of herpetic disease and significantly lower than 67 patients with a history of recurrent herpes genitalis in association with oral or peri-genital disease all of whom had neutralising antibody against both virus types. There were similar differences between groups for immunoprecipitating antibody where 80% of patients were herpes genitalis alone had no detectable immunoprecipitating antibody. The results indicate that the failure to detect immunising and immunoprecipitating antibody in an individual's serum is compatible with a long and even severe history of recurrent herpes genitalis and consequently that the development of neutralising antibody does not necessarily indicate an episode of primary herpetic disease.

Antibodies, Viral↗

[Herpes simplex virus type 1-induced rising dbl quote, left (low)tumor" in the nasal vestibule. The problem of resistance development of herpes simplex in a patient with chronic lymphatic B-cell leukemia].

Herpes simplex viruses are known to be among the most common disease-causing microorganisms. Their prevalence can exceed 90% depending on the socioeconomic status of the population. Since the number of immunocompromised patients has increased because of the increased incidence in the acquired immunodeficiency syndrome and an increase in organ transplantation, herpes virus infection may have a greater clinical significance. While treatment of otherwise healthy individuals will not usually cause any clinical problems herpes infection in an immunocompromised patient can have severe consequences. Additionally, development of viral resistance can be observed that may require alternative drugs in treatment. We present a case history of a man with a B-cell chronic lymphocytic leukemia that was associated with a very unusual herpes simplex virus infection in the nasal vestibule. Possible causes for the development of resistance in herpes infections and the use of famciclovir and forscarnet as two therapeutic alternatives to aciclovir are discussed.

Antiviral Agents↗

Thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model.

A series of 111 thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds were evaluated as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model. All derivatives tested were potent inhibitors of virus replication with mean 50% inhibitory concentrations of 1.1 micrograms/ml for both type 1 and 2 herpes simplex virus. Inhibitory concentrations for cellular protein and DNA synthesis were considerably higher for many compounds resulting in in vitro therapeutic indices ranging from greater than 100 (highly selective) to less than 1 (negatively selective). All compounds were tested for dermal toxicity following topical administration of saturated solutions in 1,3-butanediol to the shaved, depilated skin of guinea pigs. Approximately 50% of the compounds produced slight to no dermal toxicity whereas the remaining compounds produced moderate to severe dermal toxicity. 28 compounds were evaluated in the cutaneous herpes guinea pig model against herpes simplex virus type 1. A number of N4-monosubstituted 2-acetylpyridine thiosemicarbazones produced highly significant reductions in days to healing and lesion score without producing untoward dermal toxicity. Structure-activity relationships revealed that a reduction of the azomethine bond in the molecule (i.e., conversion of a thiosemicarbazone to a thiosemicarbazide) greatly diminished dermal toxicity apparently without producing a proportional decrease in antiviral activity.

Animals↗

Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis.

BACKGROUND: Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which this virus may be present in the blood during a localized infection in otherwise healthy adults is unknown. OBJECTIVE: The purpose of this study was to determine whether HSV may be detected in the peripheral blood during acute recurrent herpes labialis. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from otherwise healthy adults with recurrent herpes labialis, both during an acute episode and several weeks after the lesions had healed. The PBMCs were examined for the presence of HSV with the polymerase chain reaction (PCR) and viral culture. RESULTS: By PCR, HSV DNA was detected in 7 of 34 specimens from an acute episode but in none of 24 specimens in the convalescent stage (p less than 0.004). PBMCs from seven donors, who were seronegative for HSV, were also negative for HSV by PCR. Viral cultures of 22 PBMC specimens were negative (including four specimens that were positive by PCR). CONCLUSION: The presence of HSV DNA in the blood is a transient phenomenon limited to the period of active infection in a minority of patients with herpes labialis, although it may be important in the development of disseminated disease as well as in the pathogenesis of herpes-associated cutaneous processes such as erythema multiforme.

Acute Disease↗

Study of knowledge of genital herpes infection and attitudes to testing for genital herpes among antenatal clinic attendees.

A descriptive survey of knowledge of genital herpes and attitudes to testing was conducted among antenatal clinic attendees at the Gold Coast Hospital, Australia. The study subjects showed a good knowledge of genital herpes, to a level that appears sufficient for an informed choice regarding herpes serology testing to be made. A preference for testing for genital herpes was suggested. Although serological testing is not routinely required, the results of the study indicate that discussion of genital herpes should be considered in the antenatal clinic setting.

Adult↗