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Herpes zoster and recurrent herpes simplex.

87 patients with the clinical diagnosis of herpes zoster were seen during a one-year period in 8 general practices in Glasgow, the rate per 1 000 practice population being approximately 2.4. Of these, 78 (90%) had serological evidence of active infection with herpes zoster. A history of recurrent herpes simplex was obtained in 25 (32%) of the 78 patients with confirmed herpes zoster; 63 (81%) of these 78 had complement-fixing (CF) antibodies to herpes simplex. Thus, latent herpes simplex infection did not prevent herpes zoster nor modify the severity of herpes zoster. In most of the patients CF antibodt to varicella-zoster was not detected within 5 days from appearance of the rash. After the acute phase of the illness CF antibody titres fell fairly rapidly, the geometric mean titre being 189 at 2-4 weeks after the rash, 27 from 3-6 months, and 8 from 12-18 months. The rapid rise and decline in CF antibody after herpes zoster infection compared with the unchanging CF titres associated with recurrent herpes simplex infection suggest that varicella-zoster and herpes simplex virus differ in their mechanism of latency.

Adult↗

An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes.

Almost all neonatal herpes simplex virus infections occur as a result of first-episode maternal infection during late pregnancy when delivery occurs before the development of protective maternal antibodies. Screening of pregnant women for the presence of type-specific herpes simplex virus antibodies has therefore been suggested as a means of identifying women vulnerable to herpes simplex virus acquisition and subsequent transmission of herpes simplex virus to their neonates. Couples in whom herpes simplex virus serotype discordance is identified could be counseled regarding sexual behavior modification to avoid maternal herpes simplex virus infection. However, the ramifications of routine screening for herpes simplex virus susceptibility during pregnancy could be profound in terms of costs, prenatal care delivery, and even social duress. The recent US Food and Drug Administration approval of type-specific herpes simplex virus antibody assays for clinical use lends temporal urgency to the need for a critical examination of the relevant data. After we performed such an evaluation and created a decision analysis model to assess the potential cost-effectiveness of herpes simplex virus antibody screening, we concluded that screening for maternal type-specific herpes simplex virus antibodies cannot be recommended to prevent neonatal herpes.

Antibodies, Viral↗

Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.

BACKGROUND: Genital herpes and herpes labialis are prevalent, physically and psychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex, a highly bioavailable prodrug of acyclovir (Zovirax, and famciclovir (Famvir), a highly bioavailable prodrug of penciclovir (Denavir). OBJECTIVE: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. METHODS: All published literature containing the word "valacyclovir" was reviewed and summarized. RESULTS: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. CONCLUSION: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.

2-Aminopurine↗

The ubiquitin-like domain of Herp is involved in Herp degradation, but not necessary for its enhancement of amyloid beta-protein generation.

Herp is an endoplasmic reticulum (ER)-stress-inducible membrane protein, which has a ubiquitin-like domain (ULD). However, its biological function is as yet unknown. Previously, we reported that a high expression level of Herp in cells increases the generation of amyloid beta-protein (Abeta) and that Herp interacts with presenilin (PS). Here, we addressed the role of the ULD of Herp in Abeta generation and intracellular Herp stability. We found that the ULD is not essential for the enhancement of Abeta generation by Herp expression and the interaction of Herp with PS, but is involved in the rapid degradation of Herp, most likely via the ubiquitin/proteasome pathway. Thus, the ULD of Herp most likely plays a role in the regulation of the intracellular level of Herp under ER stress.

Acetylcysteine↗

[Incidence of herpes zoster in pediatricians and history of reexposure to varicella-zoster virus in patients with herpes zoster].

We found that pediatricians have enhanced specific cellular immunity to varicella-zoster virus (VZV) compared with the general population, which may be due to reexposure to VZV from children with chickenpox. There have been some reported that the varicella vaccine enhance the specific cellular immunity. To estimate the efficacy of varicella vaccine for protection against herpes zoster in the elderly, we investigated the incidence of herpes zoster in 500 pediatricians and family practitioners with their fifties and sixties, and history of reexposure to VZV in 61 patients with herpes zoster by questionnaires retrospectively. Thirty-four of 352 pediatricians had a past history of herpes zoster. The incidence per 100,000 person-years of herpes zoster was 65.2 in those in their fifties and 158.2 in those in their sixties, which are 1/2 to 1/8 of other reports regarding the general population. Among 61 immunocompetent patients with herpes zoster, only 4 patients (6.6%) had the chance for reexpose to VZV before their herpes zoster. Only 7 (17.5%) of the 40 patients older than 50 years of age lived with their children less than 14 years of age. Twenty-three (57.5%) of them lived without their children and grandchildren. They are thought to be less chance to reexpose to VZV through children. We may think that the booster effect by reexposure to VZV plays an important role to prevent herpes zoster. Therefore, we can speculate that the varicella vaccine may protect against herpes zoster in the elderly by the enhanced specific cellular immunity due to the booster effect.

Adolescent↗

Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes.

OBJECTIVE: To determine frequency, anatomic site, and host factors associated with asymptomatic shedding of herpes simplex virus after initial episodes of genital herpes. DESIGN: Cohort study with follow-up for a median of 63 weeks. SETTING: Referral clinic. PATIENTS: Women (306) with first episode of herpes; 43 had primary herpes simplex virus type 1, and 227 and 36 had primary and nonprimary herpes simplex virus type 2, respectively. MEASUREMENTS: Cultures were obtained for herpes simplex virus every 4 to 6 weeks at times in which genital lesions and symptoms were not present. MAIN RESULTS: Asymptomatic shedding was detected among 11.9%, 18.3%, and 22.9% of women with primary herpes simplex virus type 1, primary HSV type 2, and nonprimary HSV type 2, respectively. Among patients with type 2 infection, previous type 1 antibody was associated with a lower rate of asymptomatic vulvar shedding. Asymptomatic cervical shedding was 3 times more frequent during the first three months after resolution of primary type 2 disease than during later time periods. In contrast, the rate of symptomatic recurrent herpes did not change over time. CONCLUSIONS: Asymptomatic genital herpes simplex type 2 is more common than type 1. Asymptomatic genital shedding occurs more often during the first 3 months after acquisition of primary type 2 disease than during later periods. Patients with HSV type 2 should be advised of this high early rate of asymptomatic shedding and of potential transmission to sexual partners.

Adult↗

Exclusive involvement of folliculosebaceous units by herpes: a reflection of early herpes zoster.

The histopathological changes of herpes simplex, herpes zoster, and varicella are considered to be indistinguishable from one another. Evaluation of the clinical setting, with adjunctive studies if necessary, generally clarifies the specific diagnosis. Vesicular lesions in all three conditions can involve epidermal and adnexal epithelium with characteristic cytopathic features. We describe three patients with non-vesicular eruptions on the head and neck whose biopsies revealed exclusive folliculosebaceous involvement by herpes. All three patients developed typical herpes zoster within days of the biopsy. There is compelling scientific evidence in the literature indicating that, in herpes zoster, the virus is transported from dorsal root or trigeminal ganglia via myelinated nerves to the skin. These terminate at the isthmus of hair follicles and primary infection of follicular and sebaceous epithelium occurs. Spread of infection to the epidermis follows. In contrast, data pertaining to recurrent herpes simplex indicates that axonal transport of the virus from sensory ganglia to the skin is directed primarily to the epidermis, via terminal non-myelinated nerve twigs. The clinical evolution of our three cases and scientific data in the literature indicate that exclusive folliculosebaceous involvement by herpes, in the setting of a non-vesicular eruption, represents early herpes zoster.

Adult↗

Valacyclovir in the treatment of genital herpes and herpes zoster.

Genital herpes is prevalent and sometimes debilitating. Likewise, herpes zoster ('shingles') can be painful and often disabling. The treatment of these conditions has been advanced over the past two decades by the introduction of guanosine nucleoside antivirals such as valacyclovir (Valtrex), Glaxo Wellcome), the highly bioavailable prodrug of acyclovir (Zovirax), Glaxo Wellcome). This review describes the pharmacology, pharmacokinetics, clinical efficacy and tolerability of valacyclovir and considers its clinical attributes in the context of those of the antivirals, acyclovir and famciclovir (Famvir), SmithKline Beecham). The data demonstrate that valacyclovir is more effective than placebo and as effective as other antivirals in the episodic and suppressive treatment of recurrent genital herpes. Valacyclovir is the only antiviral shown to be effective with a short (3-day) course in the episodic treatment of recurrent genital herpes, as well as with once-daily dosing for daily suppressive therapy. In herpes zoster, valacyclovir is as effective as famciclovir and more effective than either placebo or acyclovir at facilitating cutaneous healing and healing of zoster-associated pain and post-herpetic neuralgia. Valacyclovir is well tolerated, with convenient dosing frequencies for the treatment of genital herpes or herpes zoster, it also has the option for use as a short course therapy in the episodic treatment of recurrent genital herpes, all of which are important benefits in the management of these conditions.

Acyclovir↗

Clinical reactivation of herpes simplex virus type 2 infection in seropositive pregnant women with no history of genital herpes.

OBJECTIVE: To determine the risk for genital herpes and asymptomatic herpes simplex virus (HSV) shedding in late pregnancy and delivery in a population of HSV type 2 (HSV-2)-seropositive but previously asymptomatic pregnant women. DESIGN: A prospective inception cohort study. PARTICIPANTS: A total of 1355 pregnant women with no history of genital herpes referred from three private obstetrics practices between November 1985 and June 1988. MAIN OUTCOME MEASURES: Confidential questionnaires evaluated sexual risk factors in relation to HSV-2 serologic status as determined by Western blot analysis. Herpes simplex virus shedding was determined by viral culture of the cervix and vulva and of any suspicious lesions. RESULTS: Antibody to HSV-2 was detected in 439 of 1355 pregnant women (32%) with no history of genital herpes. Asymptomatic HSV shedding was detected in 5 of 1160 cultures (0.43%) obtained in late pregnancy and during delivery. A first episode of clinical genital herpes was recognized by 43 of 264 HSV-2-seropositive women (16%) during their pregnancy. CONCLUSIONS: Serologic evidence of unknown HSV-2 infection was common in pregnant women without a history of genital herpes. Asymptomatic viral shedding in these women occurred at a rate similar to that seen in women with symptomatic genital HSV-2 infection. To improve recognition of genital herpes near term, obstetricians should counsel pregnant women about the high prevalence and mild and diverse symptoms of genital HSV-2 infection.

Adult↗

Knowledge of partners' genital herpes protects against herpes simplex virus type 2 acquisition.

BACKGROUND: Prospective studies of herpes simplex virus type 2 (HSV-2) infection in discordant couples have shown a low rate of transmission. However, unlike partners with genital herpes in prospectively monitored couples, most persons who transmit genital herpes are not aware of having the infection. METHODS: Because HSV has a short incubation period and most persons who acquire genital herpes can identify the transmitting partner, a time-to-event design was used to assess risks of HSV acquisition among patients with newly acquired genital herpes. RESULTS: Among 199 persons with laboratory-documented newly acquired genital herpes, the median duration of the sexual relationship with the transmitting partner was 3.5 months, and the median number of sex acts before transmission was 40. The median time to HSV-2 acquisition was greater among participants whose partners disclosed that they had genital herpes, compared with participants whose partners did not disclose their status (270 vs. 60 days; P = .03). In multivariate models, having a partner who disclosed that he or she had genital herpes remained a strong protective factor against genital HSV-2 acquisition (hazard ratio, 0.48 [95% confidence interval, 0.25-0.91]). CONCLUSION: These findings suggest that testing persons with HSV type-specific serologic assays and encouraging disclosure may result in a decreased risk of HSV-2 transmission to sex partners.

Adolescent↗

The psychosocial impact of testing individuals with no history of genital herpes for herpes simplex virus type 2.

BACKGROUND: Although approximately 20% of the population has a genital herpes (HSV-2) infection, 80% of these infections are unrecognized or asymptomatic. Serologic identification of HSV-2 leads to recognition of infection, which could lead to behavioral changes that reduce transmission. However, there has been concern that HSV-2 testing among persons without symptoms will cause substantial psychosocial harm. GOAL: The goal of this study was to assess the psychosocial impact of an HSV-2 diagnosis among individuals without a history of genital herpes attending a sexually transmitted disease (STD) clinic. STUDY: We conducted a cohort study of persons with no history of genital herpes attending an STD clinic and seeking herpes testing. Two follow-up interviews were conducted 1 week and 3 months after persons received their test results. Serum was tested using HerpeSelect 2. Psychosocial morbidity was assessed at baseline and each follow up using a mental health score, sexual attitude score, and perception of genital herpes score. RESULTS: Twenty-one percent (41 of 196) of participants tested positive for HSV-2 antibody. Among patients who were HSV-2-positive, there was no significant change in mental health score from baseline during either follow-up visit, nor was there any difference compared with persons who were HSV-2-negative. Patients who were HSV-2-positive did have a decline (P = 0.01) in their sexual attitude scores at the 1-week follow up compared with persons who were HSV-2-negative, indicating a decrease in positive sexual attitude, but this difference no longer remained at the 3-month follow up (P = 0.74). Patients who were HSV-2-positive viewed having genital herpes as significantly less traumatic than patients who were HSV-2-negative at both follow-up visits (P <0.01). CONCLUSION: There was no apparent lasting adverse psychosocial impact of detecting HSV-2 infection among individuals without a history of genital herpes seeking herpes testing at an STD clinic.

Adolescent↗

First episodes of genital herpes in a Swedish STD population: a study of epidemiology and transmission by the use of herpes simplex virus (HSV) typing and specific serology.

OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners. METHODS: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes. CONCLUSIONS: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.

Adolescent↗

Incidence of herpes genitalis in Northern Ireland in 1973-83 and herpes simplex types 1 and 2 isolated in 1982-4.

During 1973 - 83 there was a pronounced rise in the number of new cases of herpes genitalis in Northern Ireland. This study of 127 patients with herpes genitalis shows that 30% had herpes simplex virus type 1 (HSV 1) and 70% had herpes simplex virus type 2 (HSV 2) infections. Of 41 sexual contacts who attended, only seven had herpes genitalis (caused in each case by HSV 2); another patient had a history of genital lesions, and one other of oral lesions, but HSV was not isolated from either patient. None of the other sexual contacts had a history of oral or genital infection. Of 31 women with herpes genitalis who consented to undergoing cervical cytology, five had atypical changes (all had primary herpes genitalis). Of these, four were infected with HSV 1 and one with HSV 2.

Female↗

Cytologic examination and viral and bacterial culture in herpes simplex, herpes zoster, and varicella.

Cytologic examination of epithelial cells from the base of vesicles, virus isolation, and bacterial culture were carried out in thirty-one patients with herpes simplex, in eleven patients with herpes zoster, and in three patients with varicella. Determination of herpes simplex complement fixation reaction was made in the patients with herpes simplex. Cytologic manifestations consistent with herpes were found 65 percent of patients with herpes simplex, while herpesvirus hominis was isolated in 77 percent of these patients. Diagnostic cytologic manifestations were found in 82 percent of the patients with herpes zoster or varicella. Varicella-zoster virus was isolated in 27 percent of these patients. The presence of pathogenic bacteria did not seem to influence the frequency of virus isolation or finding of characteristic cytologic features.

Bacteria↗

Interim summary of mortality in herpes simplex encephalitis and neonatal herpes simplex virus infections: vidarabine versus acyclovir.

Herpes simplex encephalitis and neonatal herpes simplex virus infections are important consequences of herpes simplex virus infections of humans. The association of both diseases with significant mortality and morbidity has prompted intensive therapeutic trials designed to improve outcome. The NIAID Collaborative Antiviral Study Group has been able to demonstrate that vidarabine therapy decreases the mortality and improves morbidity for both herpes simplex encephalitis and neonatal herpes simplex virus infections. Nevertheless, mortality for both diseases is about 40% and many survivors are left with significant neurological impairment. With the hope of improving outcome, we initiated comparative trials of vidarabine and acyclovir for these two diseases. This report summarizes the status of these trials, which are still underway, with particular reference to the complexities of studies such as these. Because adequate numbers of patients for definitive statistical analyses have not been entered into the trial, data were assessed according to outcome for the entire group, irrespective of drug administered. The mortality of herpes simplex encephalitis and neonatal herpes simplex virus infections has been reduced to 34 and 30%, respectively, a decrease of approximately 10% for each disease. Further analyses await completion of the trials.

Acyclovir↗

Evaluation of a novel, anti-herpes simplex virus compound, acyclovir elaidate (P-4010), in the female guinea pig model of genital herpes.

The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.

Acyclovir↗