Alpha-herpes virus infections--male genital herpes

In Japan, male genital herpes is the third popular male STD, the most popular one being gonococcal infection and the second chlamydial infection. As specific clinical findings, superficial ulcer lesions with pain are formed in the genital area, especially in the prepuce. After HSV infection in genital mucocutaneous sites, viral particles are transported to the neurons. The state of subsequent HSV infection from external genitalia to the neurons is known as latent infection. 76% of our cases of the first episode of genital herpes infection were caused by HSV-2, and most of the recurrent episodes was caused by HSV-2. Oral acyclovir administration for five to ten days has shortened the treatment period, although about 20 days were required without any treatment. The remaining problems are, asymptomatic HSV shedding, severe infections in immunocompromised patients, transmission of HSV to sex partners and vertical infection to neonates.     

Current diagnostic techniques in genital herpes: their role in controlling the epidemic

Genital herpes continues to be a public health problem in both developed and developing countries. Laboratory confirmation of clinical diagnosis is important, particularly as there are other conditions which present similarly to genital herpes, while atypical presentations of genital herpes also occur. Herpes simplex virus type 2 (HSV-2) is the most common cause of genital herpes globally, although HSV-1 genital herpes infections occur also. Type-specific serology has overcome the technical problems posed by earlier cross-reactive HSV serological assays, hence HSV-2 specific antibodies can be identified using both in-house and commercial assays. All HSV-2 serological assays require an appropriately thorough validation, and here an understanding of the natural history of genital HSV infection is important. Validated HSV-2 specific antibody assays have featured in seroepidemiological studies which have emphasised the largely asymptomatic nature of this infection. Subsequent seroepidemiological studies have included a sexual lifestyle questionnaire to identify risk factors for genital HSV-2 infection. This has given rise to serological screening proposals which, it is argued, may arrest the spread of genital herpes in the general population. However, counter arguments to such proposals are important to consider. As regards diagnosis and management of genital herpes in individual patients, situations have been identified where type-specific serology may be of benefit. PCR has become the method of laboratory diagnosis for HSV encephalitis over the past decade, but its role in the diagnosis of genital herpes has been addressed only in recent years. Evaluation of HSV PCR on specimens from genital herpes cases has shown PCR to be more sensitive than virus culture, the traditional "gold standard" of HSV identification. However, questions remain regarding the acceptance of HSV into routine diagnostic settings, particularly concerning sample preparation, although automation and the ability to include diagnosis of other genital infections in a multiplex PCR is an advantage. Such developments should enhance the role of PCR in genital herpes diagnosis and ultimately reduce costs relative to traditional methods such as culture and HSV antigen detection. Finally, the use of type-specific serology and HSV PCR in genital herpes research is noted.     

Recurrent genital infection in the guinea pig: differences between herpes simplex types 1 and 2.

Recurrence rates of genital infections are significantly higher for herpes simplex virus (HSV) type 2 than HSV type 1. Reasons for this difference are not known. In this report, multiple strains of HSV-1 and HSV-2 were evaluated in the guinea-pig model. HSV-2 strains showed significantly higher genital lesion recurrence than HSV-1, including HSV-1 McKrae strain which is highly recurrent in ocular infections. HSV-2 strains were also associated with more frequent asymptomatic vaginal virus shedding. Further study showed that HSV-1 strains replicated as well as HSV-2 in both the genital tract and the nervous system during acute infection. In addition, no difference was detected between HSV-1 and HSV-2 in nervous system latency. Thus, a number of possible explanations for the observed difference in genital herpes recurrence rates were examined and excluded.     

Topical microbicides for the prevention of genital herpes infection

Genital herpes is one of the most prevalent sexually transmitted infections worldwide and is the most common cause of genital ulcers. Despite increased public awareness and the initiation of efforts to prevent transmission, the prevalence of herpes simplex virus (HSV) type 2 continues to increase. What makes HSV so difficult to control is that most sexual and perinatal transmission occurs during unrecognized or asymptomatic shedding. The impact of genital herpes as a public health threat is amplified because of its epidemiological synergy with HIV/AIDS. Thus, there is an urgent need for novel prophylactic methods, such as topical microbicides designed for genital application, to prevent both HSV and HIV transmission. Several candidate microbicides are being advanced to clinical trials based on in vitro activity and animal studies. These include compounds that inactivate virus directly, those that enhance innate immunity, and drugs that block viral binding and entry. A more vigorous evaluation of the safety of these and other candidate topical microbicides in development should include assessment of the impact of repeated application on innate host defences in the genital tract.     

Genital herpes simplex virus type 1 infection: new fields for an old acquaintance?

Herpes simplex virus (HSV)-2 is the principal agent of chronic remittent genital herpes. Worldwide, only 10-20% of genital isolates are HSV-1. Studies from the British Isles and Scandinavia indicate, however, that HSV-1 is responsible for a significant proportion or even the majority of first clinical episodes of genital herpes in young women. Actual data show that a trend towards genital HSV-1 infections may also hold true for Germany. This article summarizes possible reasons for and consequences of the observed changes in the epidemiology of genital HSV infections.     

Valacyclovir for the treatment of genital herpes

Genital herpes is the most prevalent sexually transmitted infection in the USA. While sometimes mild in severity, it can be a distressing and painful chronic condition. Likewise, herpes labialis and herpes zoster can be both physically and psychologically painful. While there is no cure for these conditions, treatment to alleviate symptoms, suppress recurrences and reduce transmission has been drastically improved over the past 20 years with the use of guanine nucleoside antivirals, such as valacyclovir hydrochloride (Valtrex), GlaxoSmithKline) the highly bioavailable prodrug of acyclovir (Zovirax((R)), GlaxoSmithKline), and famciclovir (Famvir, Novartis), a highly bioavailable prodrug of penciclovir (Denavir, Novartis). Clinical trials involving approximately 10,000 patients (including patients from nongenital herpes studies, such as herpes zoster) have assessed the safety and efficacy of valacyclovir in the treatment of initial genital herpes outbreaks, episodic treatment of recurrent episodes and daily suppressive therapy. It was shown that valacyclovir has similar efficacy to acyclovir in the episodic and suppressive treatment of genital herpes. Valacyclovir is the only antiviral drug approved for a once-daily dose of suppressive therapy for genital herpes, as well as the only antiviral drug US FDA approved for a 3-day regimen of episodic treatment of recurrent genital herpes. In addition, valacyclovir is also indicated in the reduction of the sexual transmission of herpes simplex virus infection and for the treatment of herpes labialis. In herpes zoster, valacyclovir is more effective than acyclovir or placebo (and as equally effective as famciclovir) in shortening the length and severity of herpes zoster-associated pain and postherpetic neuralgia. Valacyclovir has an acceptable safety profile in patients with herpes simplex and herpes zoster. The less frequent dosing regimen makes it an attractive option in the treatment of genital herpes and other viral infections, and may contribute to increased patient adherence to therapy.     

Type-specific testing for herpes simplex virus

The prevalence of genital herpes is increasing worldwide. Type-specific antibody tests for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are widely available, however, only those based on glycoprotein G have acceptable accuracy. When diagnosing genital herpes, it is important to use type-specific tests in order to distinguish HSV-1 from HSV-2 since the type of HSV infection affects prognosis and subsequent counseling. Populations appropriate for type-specific serologic testing for HSV include people with an uncertain clinical diagnosis, high-risk patients, partners of an HSV-infected individual, HIV-infected individuals and pregnant women.     

Sexually transmitted diseases of alpha herpes virus in women

Among two alpha herpes viruses, Herpes Simplex Virus(HSV) and Varicella Zoster virus(VZV), HSV infects genital sites and is frequently transmitted by sexual contact while VZV has quite different mode of transmission and rarely infects genital site except herpes zoster at the vulva. Genital herpes is the second and the third leading cause of STDs in women and men respectively. While 90% of male genital herpes was caused by HSV-2, 55% of female genital herpes was by HSV-2 and the remaining 45% by HSV-1. As for primary infection of female genital herpes, 60% was caused by HSV-1 and 40% by HSV-2. On the otherhand about 90% of recurrent infection was by HSV-2 suggesting that HSV-2 is closely related to latent infection of the female genital tract.     

Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster

Acyclovir (Zovirax) was approved for the treatment of herpesvirus infections almost two decades ago. It was the first agent in a novel group of antiviral medications that now include valacyclovir (Valtrex), penciclovir (Denavir and famciclovir (Famvir). These agents have made a dramatic impact on the morbidity associated with herpes simplex virus infections and herpes zoster. Topical and oral antiviral use have shown modest but statistically significant efficacy in treating herpes labialis with most studies demonstrating a significant reduction in episode length and/or healing time. Oral acyclovir, valacyclovir and famciclovir are efficacious and safe for the treatment of the first episode and recurrent genital herpes and are useful as suppressive therapy for individuals with frequent genital herpes recurrences. In addition, high doses of oral acyclovir, valacyclovir and famciclovir have been shown to speed the healing of herpes zoster, and data suggests that these agents also decrease associated acute and chronic pain in people of 50 years of age or older. Further research is required to clarify the safety of these agents in pregnant women with genital herpes, the role of antiviral therapy in decreasing the sexual transmission of genital herpes, and the efficacy and cost-effectiveness of these agents in treating herpes zoster in people below the age of 50 years.     

Neonatal herpes simplex virus infections

Neonatal herpes simplex virus infections can result in serious morbidity and mortality. Many of the infections result from asymptomatic cervical shedding of virus after a primary episode of genital HSV in the third trimester. Antibodies to HSV-2 have been detected in approximately 20 percent of pregnant women, but only 5 percent report a history of symptomatic infection. All primary episodes of HSV and secondary episodes near term or at the time of delivery should be treated with antiviral therapy. If active HSV infection is present at the time of delivery, cesarean section should be performed. Symptomatic and asymptomatic primary genital HSV infections are associated with preterm labor and low-birth-weight infants. The diagnosis of neonatal HSV can be difficult, but it should be suspected in any newborn with irritability, lethargy, fever or poor feeding at one week of age. Diagnosis is made by culturing the blood, cerebrospinal fluid, urine and fluid from eyes, nose and mucous membranes. All newborns suspected to have or who are diagnosed with HSV infection should be treated with parenteral acyclovir.     

Seroepidemiology of alphaherpesviruses

The seroepidemiology of herpes simplex virus (HSV) type-1 and -2 was studied in different Japanese populations, by applying HSV gG1 and gG2 type-specific antibody assays. HSV-1 infections correlated mostly with age and was widely prevalent among subjects over 40 years old. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and were associated with risk behaviors, from 80% among prostitutes to 7% among pregnant women. Since HSV-1 infection during childhood has been decreasing, primary genital HSV-1 or HSV-2 infection, with its higher frequency of clinical manifestations, will become more important. In contrast, antibody prevalence to varicella-zoster virus has been constantly high in children, with no tendency to change in seroepidemiology of VZV infections so far.     

Clinical assessment of assays for diagnosis of herpes simplex infection

It is becoming increasingly clear that the herpes simplex viruses (HSVs) 1 and 2 constitute a major, global, public health problem, particularly as genital herpes is implicated in the causation of a significant percentage of onwards transmission of the HIV virus. A major factor in the transmission of HSV is that most carriers are unaware of their diagnosis. In the last few years, the development of nucleic acid amplification technology and type-specific antibody serology to test for HSV-1 and -2 has contributed significantly to the accurate diagnosis of these infections. Despite guidance to the contrary, there is still much use of less sensitive tests such as viral culture and antibody testing based on crude antigen. It is essential that we use the most sensitive and specific diagnostic tests if we are to curb this epidemic.     

Comparison of intramuscular recombinant alpha interferon (rIFN-2A) with topical acyclovir for the treatment of first-episode herpes genitalis and prevention of recurrences.

Intramuscular recombinant alpha interferon (rIFN-2A; 9 million IU given for 5 days during a 9-day treatment period) was compared with topical acyclovir in a double-blind, placebo-controlled trial for the treatment of first-episode genital herpes simplex virus (HSV) infection and for subsequent alteration of the frequency of recurrences. rIFN-2A (within 96 h of onset of the first episode) was not superior to topical acyclovir in a well-matched group of 105 patients. The early use of rIFN-2A also did not alter the frequency or severity of genital HSV recurrences within either the first or second 6 months following therapy. Separate analyses by HSV type and by type of infection (primary versus nonprimary) did not change this conclusion. Furthermore, there was significant toxicity associated with rIFN-2A therapy. rIFN-2A is not indicated for the treatment of genital HSV infections.     

Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs.

Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in vivo anti-herpesvirus activity by inducing interferon and enhancing other only partially defined immune responses. Imiquimod treatment of primary genital herpes simplex virus (HSV) infection in guinea pigs reduces the level of genital disease by 90%. We further investigated its utility as suppressive therapy of recurrent disease in animals that had recently recovered from primary genital HSV-2 disease. Imiquimod administered intravaginally once per day for 5 days reduced the number of recurrences only during treatment, while a 21-day regimen reduced the number of recurrences for 8 weeks. For the entire 10 weeks of observation, overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased circulating alpha interferon activity was observed during therapy with both regimens. Interferon levels rapidly returned to baseline with cessation of treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day imiquimod treatment reduced both the number of clinical recurrences and levels of HSV antibody for 5 to 6 weeks posttreatment compared with the placebo. Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific interleukin 2 production and proliferative responses by mononuclear cells (P < 0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed recurrent HSV genital disease during and for weeks after therapy, enhanced memory-dependent cytokine and T-cell responses, and reduced the level of antibody responses.     

Review of antiviral therapy for herpes labialis,genital herpes and herpes zoster

Acyclovir (Zovirax^®) was approved for the treatment of herpesvirus infections almost two decades ago. It was the first agent in a novel group of antiviral medications that now include valacyclovir (Valtrex^®), penciclovir (Denavir^®) and famciclovir (Famvir^®). These agents have made a dramatic impact on the morbidity associated with herpes simplex virus infections and herpes zoster. Topical and oral antiviral use have shown modest but statistically significant efficacy in treating herpes labialis with most studies demonstrating a significant reduction in episode length and/or healing time. Oral acyclovir, valacyclovir and famciclovir are efficacious and safe for the treatment of the first episode and recurrent genital herpes and are useful as suppressive therapy for individuals with frequent genital herpes recurrences. In addition, high doses of oral acyclovir, valacyclovir and famciclovir have been shown to speed the healing of herpes zoster, and data suggests that these agents also decrease associated acute and chronic pain in people of 50 years of age or older. Further research is required to clarify the safety of these agents in pregnant women with genital herpes, the role of antiviral therapy in decreasing the sexual transmission of genital herpes, and the efficacy and cost-effectiveness of these agents in treating herpes zoster in people below the age of 50 years.     

Prevention,recognition and management of neonatal HSV infections

Neonatal HSV is most commonly transmitted at the time of delivery with the risk being dramatically higher if the mother has first-episode genital HSV and does not have an elective Cesarean section. Maternal HSV type-specific serology can be used to differentiate first-episode from recurrent infection in this setting, allowing for use of empiric acyclovir for the highest risk infants. There is a need for new strategies as current methods of prevention of transmission of HSV to neonates have limited effectiveness, as they do not account for the fact that the majority of transmission occurs from asymptomatic women. After transmission has occurred, early recognition of neonatal HSV improves the prognosis. Diagnosis needs to be considered in all infants who develop vesicles, unexplained seizures, or possible sepsis in the first 5 weeks of life.     

Prevention, recognition and management of neonatal HSV infections

Neonatal HSV is most commonly transmitted at the time of delivery with the risk being dramatically higher if the mother has first-episode genital HSV and does not have an elective Cesarean section. Maternal HSV type-specific serology can be used to differentiate first-episode from recurrent infection in this setting, allowing for use of empiric acyclovir for the highest risk infants. There is a need for new strategies as current methods of prevention of transmission of HSV to neonates have limited effectiveness, as they do not account for the fact that the majority of transmission occurs from asymptomatic women. After transmission has occurred, early recognition of neonatal HSV improves the prognosis. Diagnosis needs to be considered in all infants who develop vesicles, unexplained seizures, or possible sepsis in the first 5 weeks of life.     

Clinical and subclinical reactivation of genital herpes virus

Reactivations of herpes simplex virus (HSV) either symptomatically (recrudescence) or without symptoms (recurrence) are well documented. As an asymptomatic reactivation may contribute to transmitting HSV to potential acceptors the frequency of reactivations should be evaluated. In order to evaluate the frequency of HSV-2 reactivation 173 genital swabs of a group of women chosen at random were analyzed by nested PCR. 34 (19.6%) showed clinical evidence of a herpes infection, 77 (44.5%) had no symptoms at all and 62 (35.8%) had other symptoms. In 26 (15%) HSV-DNA was detected. 11 (38.4%) could be characterized as asymptomatic reactivations. Typing of the HSV-positive swabs resulted in 11 HSV-2 and 10 HSV-1 strains. Additionally 18 HSV-positive swabs of the oral cavity resulted in 15 (83.2%) HSV-1 and 3 (16.4%) HSV-2 strains. The results of typing indicate a change of HSV-1 and HSV-2 epidemiology.     

Genital Herpes: Diagnosis,Treatment, and Counseling in the Adolescent Patient

Genital herpes is one of the most prevalent sexually transmitted infections. An estimated 22% of the U.S. population older than 14 years is infected with herpes simplex virus-2 (HSV), with an additional 1.6 million new infections per year. The presentation of an infection can range from classic (multiple, painful, small vesicles on an erythematous base) to asymptomatic, and can be confused with a myriad of other conditions (urinary tract infections, candidiasis, bug bites). Diagnosis requires a combination of clinical presentation and laboratory studies. In addition, a diagnosis of HSV can have a profound psychological effect and must be tailored to the individual patient. The Centers for Disease Center (CDC) recommends initial and continued counseling regarding HSV and its treatment. This article reviews the diagnosis, treatment, and counseling of HSV genital infection in the adolescent.     

单纯疱疹病毒感染抗体IgG浓度水平的动态观察

目的 探讨单纯疱疹病毒（herpes simplex virus,HSV）感染后机体IgG抗体水平的变化规律.方法 对21例有症状生殖器疱疹患者和10例无症状单纯疱疹病毒携带者定期于第1、2、3、6、9、和12月抽取静脉血2ml,用ELISA定量方法测定其抗体浓度水平.结果 21例有症状生殖器疱疹患者的第1、2、3、6、9、和12月HSV1-IgG抗体浓度（RU/ml）分别是：160±56.72 、167±55.90、165±55.03、163±62.10、161±62.28以及158±59.67;HSV2-IgG抗体浓度（RU/ml）分别：139±82.52、136±85.01、130±80.81、140±82.81、132±78.00以及132±83.52.10例无症状单纯疱疹病毒携带者的第1、2、3、6、9、和12月HSV1-IgG抗体浓度（RU/ml）分别是：120±46.31、122±42.72、113±39.93、107±39.95、107±39.95以及101±48.58;HSV2-IgG抗体浓度（RU/ml）分别是：133±60.15、123.6±53.72、115.5±47.58、98±48.63、59±40.00 以及36±43.93.结论 有症状生殖器疱疹患者的HSV1-IgG抗体和HSV2-IgG抗体浓度在一年内的观察没明显的变化;无症状单纯疱疹携带者的HSV1-IgG抗体浓度在一年内的观察没明显的变化,HSV2-IgG抗体浓度在前6个月也没明显的变化,9个月开始有浓度明显的降低,HSV2-IgG抗体水平的变化有利于生殖器疱疹的复发和再发的判断.