First-episode Genital Herpes Research Articles

Viral Shedding 1 Year Following First-Episode Genital HSV-1 Infection

Herpes simplex virus type 1 (HSV-1) is the leading cause of first-episode genital herpes in many countries. To inform counseling messages regarding genital HSV-1 transmission, oral and genital viral shedding patterns among persons with first-episode genital HSV-1 infection were assessed. The trajectory of the development of HSV-specific antibody and T-cell responses was also characterized. Prospective cohort followed up for up to 2 years, with 82 participants followed up between 2013 and 2018. Participants were recruited from sexual health and primary care clinics in Seattle, Washington. Persons with laboratory-documented first-episode genital HSV-1 infection, without HIV infection or current pregnancy, were referred for enrollment. First-episode genital HSV-1 infection. Genital and oral HSV-1 shedding and lesion rates at 2 months, 11 months, and up to 2 years after initial genital HSV-1 infection. Participants self-collected oral and genital swabs for HSV polymerase chain reaction testing for 30 days at 2 and 11 months and up to 2 years after diagnosis of genital HSV-1. Blood samples were collected at serial time points to assess immune responses to HSV-1. Primary HSV-1 infection was defined as absent HSV antibody at baseline or evolving antibody profile using the University of Washington HSV Western Blot. HSV-specific T-cell responses were detected using interferon γ enzyme-linked immunospot. Among the 82 participants, the median (range) age was 26 (16-64) years, 54 (65.9%) were women, and 42 (51.2%) had primary HSV-1 infection. At 2 months, HSV-1 was detected from the genital tract in 53 participants (64.6%) and in the mouth in 24 participants (29.3%). Genital HSV-1 shedding was detected on 275 of 2264 days (12.1%) at 2 months and declined significantly to 122 of 1719 days (7.1%) at 11 months (model-predicted rate, 6.2% [95% CI, 4.3%-8.9%] at 2 months vs 3.2% [95% CI, 1.8%-5.7%] at 11 months; relative risk, 0.52 [95% CI, 0.29-0.93]). Genital lesions were rare, reported on 65 of 2497 days (2.6%) at 2 months and 72 of 1872 days (3.8%) at 11 months. Oral HSV-1 shedding was detected on 88 of 2247 days (3.9%) at 2 months. Persons with primary HSV-1 infection had a higher risk of genital shedding compared with those with nonprimary infection (model-predicted rate, 7.9% [95% CI, 5.4%-11.7%] vs 2.9% [95% CI, 1.7%-5.0%]; relative risk, 2.75 [95% CI, 1.40-5.44]). Polyfunctional HSV-specific CD4+ and CD8+ T-cell responses were maintained during the follow-up period. Genital HSV-1 shedding was frequent after first-episode genital HSV-1, particularly among those with primary infection, and declined rapidly during the first year after infection.

Comparison of herpes simplex virus 1 genomic diversity between adult sexual transmission partners with genital infection.

Herpes simplex virus (HSV) causes chronic infection in the human host, characterized by self-limited episodes of mucosal shedding and lesional disease, with latent infection of neuronal ganglia. The epidemiology of genital herpes has undergone a significant transformation over the past two decades, with the emergence of HSV-1 as a leading cause of first-episode genital herpes in many countries. Though dsDNA viruses are not expected to mutate quickly, it is not yet known to what degree the HSV-1 viral population in a natural host adapts over time, or how often viral population variants are transmitted between hosts. This study provides a comparative genomics analysis for 33 temporally-sampled oral and genital HSV-1 genomes derived from five adult sexual transmission pairs. We found that transmission pairs harbored consensus-level viral genomes with near-complete conservation of nucleotide identity. Examination of within-host minor variants in the viral population revealed both shared and unique patterns of genetic diversity between partners, and between anatomical niches. Additionally, genetic drift was detected from spatiotemporally separated samples in as little as three days. These data expand our prior understanding of the complex interaction between HSV-1 genomics and population dynamics after transmission to new infected persons.

A holistic perspective on herpes simplex virus (HSV) ecology and evolution.

Herpes simplex viruses (HSV) cause chronic infection in humans that are characterized by periodic episodes of mucosal shedding and ulcerative disease. HSV causes millions of infections world-wide, with lifelong bouts of viral reactivation from latency in neuronal ganglia. Infected individuals experience different levels of disease severity and frequency of reactivation. There are two distantly related HSV species, with HSV-1 infections historically found most often in the oral niche and HSV-2 infections in the genital niche. Over the last two decades, HSV-1 has emerged as the leading cause of first-episode genital herpes in multiple countries. While HSV-1 has the highest level of genetic diversity among human alpha-herpesviruses, it is not yet known how quickly the HSV-1 viral population in a human host adapts over time, or if there are population bottlenecks associated with viral reactivation and/or transmission. It is also unknown how the ecological environments in which HSV infections occur influence their evolutionary trajectory, or that of co-occurring viruses and microbes. In this review, we explore how HSV accrues genetic diversity within each new infection, and yet maintains its ability to successfully infect most of the human population. A holistic examination of the ecological context of natural human infections can expand our awareness of how HSV adapts as it moves within and between human hosts, and reveal the complexity of these lifelong human-virus interactions. These insights may in turn suggest new areas of exploration for other chronic pathogens that successfully evolve and persist among their hosts.

Time Trends in First-Episode Genital Herpes Simplex Virus Infections in an Urban Sexually Transmitted Disease Clinic.

Genital herpes simplex virus type 1 (HSV-1) has emerged as the leading cause of first-episode genital herpes among specific populations in the United States, such as adolescents, young adult women, and men who have sex with men (MSM). We examined trends in the etiology of first-episode genital herpes diagnoses over time in a sexually transmitted disease (STD) clinic population. Using an electronic database, we identified persons diagnosed as having first-episode genital herpes at Public Health - Seattle & King County STD Clinic from 1993 to 2014 and compared risk factors for genital HSV-1 versus herpes simplex virus type 2 (HSV-2) infection. Of 52,030 patients with genital ulcers, 3065 (6.15%) had first-episode genital herpes infection: 1022 (33.3%) with HSV-1 and 2043 (67.7%) with HSV-2. Overall, 1154 (37.7%) were women, the median age was 28 years (interquartile range, 24-36 years), 1875 (61.2%) patients were white, and 353 (11.5%) were MSM. The number of patients diagnosed as having first-episode genital HSV-2 declined on average by 5.5 persons per year, from 208 in 1993 to 35 in 2014 (change of -5.6 per year; 95% confidence interval [CI], -6.9 to -4.1), whereas HSV-1 diagnoses remained stable at approximately 50 per year (change of 0.2; 95% CI, -0.4 to 0.9). In a multivariate model, persons diagnosed as having first-episode genital HSV-1 rather than genital HSV-2 infection were more likely to be younger (age <30 years [relative risk {RR}, 1.38; 95% CI, 1.22-1.55]), white (RR, 3.16; 95% CI, 2.57-3.88), and MSM (RR, 1.50; 95% CI, 1.31-1.71). We observed a significant decrease in the frequency of first-episode genital HSV-2 and a stable number of first-episode genital HSV-1 infections in a STD clinic over the last 2 decades.

First-episode genital herpes: interventions for men and women.

The mission of the Cochrane Nursing Care Field (CNCF) is to improve health outcomes through increasing the use of the Cochrane Library and supporting Cochrane's role by providing an evidence base for nurses and healthcare professionals who deliver, lead or research nursing care. The CNCF produces Cochrane Corner columns, summaries of recent nursing-care-relevant Cochrane Reviews that are regularly published in collaborating nursing-related journals. Information on the processes CNCF has developed can be accessed at: cncf.cochrane.org/evidence-transfer-program-review-summaries. This is a Cochrane review summary of: Heslop R, Roberts H, Flower D et al ( 2016 ) Interventions for men and women with their first episode of genital herpes. Cochrane Database of Systematic Reviews. Issue 8. CD010684. doi: 10.1002/14651858.CD010684.pub2.

Interventions for men and women with their first episode of genital herpes

Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode. To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases. We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection. All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators. We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I(2) = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies.There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I(2) statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes.Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo. There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse.

P96 Access of level 2 sexual health services by men who have sex with men: who goes and what services do they get?

<h3>Background</h3> Men who have sex with men (MSM) bear a disproportionate burden of sexually transmitted infections (STIs) including HIV. While routine STI surveillance data indicate MSM regularly access genitourinary medicine (GUM) services for their sexual health care, the extent to which MSM attend non-specialist Level 2 sexual health services is unclear. We investigated access of Level 2 services by MSM in England. <h3>Methods</h3> We used provisional data from the GUM Clinic Activity Dataset (GUMCADv2) to compare the characteristics, service usage and outcomes between MSM accessing GUM and Level 2 services who reported data in 2013. <h3>Results</h3> Of all male attendances where sexual orientation was recorded, 12.3% (6,957/57,048) of Level 2 attendances were among MSM compared to 26.3% (299,456/1,139,424) of GUM attendances (p &lt; 0.001). MSM attending Level 2 compared to GUM services, were younger (mean age: 30.5 yrs vs 38.5 yrs; p &lt; 0.001), and more likely to be of black ethnicity (6.8% vs 4.1%; p &lt; 0.001) and reside in London (49.9% vs 46.0%; p &lt; 0.001). MSM attending non-GUM services were more likely to have a full sexual health screen (41.4% vs 27.0%; p &lt; 0.001), HIV test (8.9% vs 7.1%; p &lt; 0.001), and be diagnosed with chlamydia (6.2% vs 3.0%; p &lt; 0.001), gonorrhoea (5.6% vs 4.6%: p &lt; 0.001) and first-episode genital warts (1.5% vs 1.0%: p &lt; 0.001). There was no significant difference in the proportion newly diagnosed with HIV (0.57% vs 0.69%; p = 0.268) or first-episode genital herpes (0.47% vs 0.46%; p = 0.830). <h3>Conclusion</h3> Level 2 sexual health services play an important role in the sexual health care of MSM, especially those of younger age.

Mother-to-Child Transmission of Herpes Simplex Virus.

Infections with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), both alpha herpesviruses, are highly prevalent worldwide. Both HSV types commonly cause genital infection, which, when acquired or reactivated during pregnancy, carries with it the risk of transmission to the fetus or neonate. Women who acquire primary or first-episode genital herpes during pregnancy are at greater risk for transmitting the infection than are women with recurrent genital herpes. Because viral infection and reactivation are frequently asymptomatic, many affected women are unaware of their infection and risk of transmission to their infants. Neonatal HSV infection can have devastating long-term consequences, especially when the central nervous system (CNS) is involved. Treatment of affected neonates with intravenous acyclovir has improved outcomes but there is room for further improvement, especially in regard to CNS disease. Working with pregnant women to prevent mother-to-child transmission of HSV is an important component in reducing the overall disease burden of neonatal HSV infections.

Asymptomatic Shedding of Herpes Simplex Virus 1 and 2: Implications for Prevention of Transmission

It is counterintuitive that sexual transmission of herpes simplex virus (HSV) more commonly results from contact during a short episode of asymptomatic shedding than from contact with lesions. After all, virus titers are much higher and the average duration of shedding is much longer when lesions are present [1, 2], and the risk of transmission following a single contact with lesions is undoubtedly much higher than a single contact with asymptomatic shedding. More than 2 decades ago, the role of asymptomatic shedding in transmission of HSV was suggested by evaluation of recent sex partners implicated in transmission of genital herpes and by evaluation of mothers who transmitted HSV to neonates yet lacked a history of genital herpes [3-6]. In a study published in 1985, recent sex partners of persons with first-episode genital herpes were interviewed and eval-

A Replication-Competent, Neuronal Spread-Defective, Live Attenuated Herpes Simplex Virus Type 1 Vaccine

Herpes simplex virus type 1 (HSV-1) produces oral lesions, encephalitis, keratitis, and severe infections in the immunocompromised host. HSV-1 is almost as common as HSV-2 in causing first episodes of genital herpes, a disease that is associated with an increased risk of human immunodeficiency virus acquisition and transmission. No approved vaccines are currently available to protect against HSV-1 or HSV-2 infection. We developed a novel HSV vaccine strategy that uses a replication-competent strain of HSV-1, NS-gEnull, which has a defect in anterograde and retrograde directional spread and cell-to-cell spread. Following scratch inoculation on the mouse flank, NS-gEnull replicated at the site of inoculation without causing disease. Importantly, the vaccine strain was not isolated from dorsal root ganglia (DRG). We used the flank model to challenge vaccinated mice and demonstrated that NS-gEnull was highly protective against wild-type HSV-1. The challenge virus replicated to low titers at the site of inoculation; therefore, the vaccine strain did not provide sterilizing immunity. Nevertheless, challenge by HSV-1 or HSV-2 resulted in less-severe disease at the inoculation site, and vaccinated mice were totally protected against zosteriform disease and death. After HSV-1 challenge, latent virus was recovered by DRG explant cocultures from <10% of vaccinated mice compared with 100% of mock-vaccinated mice. The vaccine provided protection against disease and death after intravaginal challenge and markedly lowered the titers of the challenge virus in the vagina. Therefore, the HSV-1 gEnull strain is an excellent candidate for further vaccine development.

Suppressive Therapy With Valacyclovir in Early Genital Herpes: A Pilot Study of Clinical Efficacy and Herpes-Related Quality of Life

Suppressive therapy has not been studied during the first year after acquisition of genital herpes, the time of maximum frequency of reactivation, potential for transmission, and impact on quality of life. The objective of this study was to evaluate the effectiveness of suppressive therapy with valacyclovir initiated within 3 months of infection. The authors conducted a double-blind, randomized, controlled trial of 1.0 g valacyclovir daily versus placebo for 6 months in 119 patients. Herpes simplex virus (HSV) type 2 and HSV-1 were documented in 75 and 22 patients, respectively. In intention-to-treat analysis, annualized rates of symptomatic recurrences for valacyclovir and placebo, respectively, were 1.7 +/- 2.7 (mean +/- standard deviation) and 3.4 +/- 4.0 outbreaks per year (P = 0.012). Time to first recurrence was 80 +/- 47 days for valacyclovir and 54 +/- 49 days for placebo (P = 0.001). The differences in favor of valacyclovir were greatest in patients with confirmed HSV-2 infection. The Recurrent Genital Herpes Quality of Life score in HSV-2 infected patients rose 11.9 +/- 11.1 points for valacyclovir and 5.9 +/- 9.1 points for placebo (P = 0.040). Early suppressive therapy with valacyclovir reduces symptomatic recurrent outbreaks, especially in patients with HSV-2 infection. Valacyclovir therapy was associated with improved herpes-related quality of life.

Herpes simplex virus type 1 remains the principal cause of initial anogenital herpes in Edinburgh, Scotland.

The goal of this study was to investigate the trends in the prevalence of anogenital herpes caused by herpes simplex virus (HSV) type-1 and HSV-2 among patients attending a sexually transmitted infections clinic. We conducted a retrospective study of virologically proven first-episode genital herpes diagnosed in the Department of Genitourinary Medicine in Edinburgh between 1989 and 2002. First-episode anogenital herpes was associated with HSV-1 in 659 (62%) women and 294 (42%) men (P <0.0002). HSV-1 was recovered more often from women younger than 25 years than from older women (P <0.0005). For both HSV-1 and HSV-2 infections, the median ages of heterosexual men (26.0 and 28.0 years, respectively) were significantly higher than those of women (23.0 and 25.0 years, respectively)(P <0.05). The median age of men who have sex with men with HSV-1 (29.0 years) was significantly higher than that of heterosexual men (26.0 years)(P <0.01). HSV-1 remains the most common cause of symptomatic first-episode anogenital herpes, especially among young women in our clinic population.

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...

Virus de l'immunodéficience humaine: actualités en maternité

Identify measures to diagnose, prevent, and treat genital herpes infection during pregnancy and childbirth as well as neonatal herpes infection.Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines.Genital herpes lesions are most often due to HSV-2 (LE2). The risk of HSV seroconversion during pregnancy is 1–5% (LE2). Genital herpes lesions during pregnancy in a woman with a history of genital herpes is a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In pregnant women with genital lesions who report they have not previously had genital herpes, virological confirmation by PCR and identifying the specific IgG type is necessary (professional consensus). A first episode of genital herpes during pregnancy should be treated with aciclovir (200 mg 5 times daily) or valaciclovir (1000 mg twice daily) for 5–10 days (Grade C), and recurrent herpes during pregnancy with aciclovir (200 mg 5 times daily) or valaciclovir (500 mg twice daily) (Grade C). The risk of neonatal herpes is estimated at between 25% and 44% if a non primary and primary first genital herpes episode is ongoing at delivery (LE2) and 1% for a recurrence (LE3). Antiviral prophylaxis should be offered to women with either a first or recurrent episode of genital herpes during pregnancy from 36 weeks of gestation until delivery (Grade B). Routine prophylaxis is not recommended for women with a history of genital herpes but no recurrence during pregnancy (professional consensus). A cesarean delivery is recommended if a first episode of genital herpes is suspected (or confirmed) at the onset of labor (Grade B) or if it occured less than 6 weeks before delivery (professional consensus) or in the event of premature rupture of the membranes at term. When a recurrence of genital herpes is underway at the onset of labor, cesarean delivery is most likely to be considered when the membranes are intact and vaginal delivery in cases of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most cases of neonatal herpes, mothers have no history of genital herpes (LE3). When neonatal herpes is suspected, various samples (blood and cerebrospinal fluid) for HSV PCR must be taken to confirm the diagnosis (professional consensus). Any newborn with suspected neonatal herpes should be treated with intravenous acyclovir (20 mg/kg 3 times daily) (grade A) before the PCR results are available (professional consensus). The duration of the treatment depends on the clinical form (professional consensus)There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes and the risk of recurrence at term, as well as cesarean rate because of herpes lesions.

HSV-2 specific serology should be offered routinely to antenatal patients.

The most devastating consequence of genital herpes is neonatal herpes. It is clear that the majority of newborns acquire their infection by contact with infected genital secretions during delivery from an asymptomatic mother who acquired a first episode of genital herpes near the time of labour. Since the majority of cases of first episode genital herpes during pregnancy are unrecognised, the prevention of neonatal transmission will depend upon the identification of the HSV serologically discordant couple and the institution of appropriate interventions by mid pregnancy. Therefore, the précis of this discussion paper is that universal HSV serological testing should be performed at the first prenatal visit. As a corollary, type specific HSV serology will need to be commercially available and relatively inexpensive. In any country, pregnant women and their partners represent a broad, cross section of sexually active adults. The vast majority present themselves to the health care system for care during their pregnancies which is a period of time in which the focus of care is primarily preventive and during which women are generally motivated and compliant. This is truly the 'golden opportunity' to identify patients already infected as well as those at risk for acquiring genital herpes. Information regarding genital herpes and methods of preventing transmission to susceptible partners and newborn infants can easily be added to educational programmes which have already become an institution within prenatal care.

Do we need antivirals for genital herpes simplex virus and human papillomavirus infection?

Genital herpes simplex virus (HSV) and human papillomavirus (HPV) infections are two widespread infections that are hardly recognized by the public as sexually transmitted diseases (STD). According to a survey of the American Social Health Association only 17% of adults recognize genital herpes as a STD and only 3% are aware of genital warts being sexually transmitted [1]. About 500 000 cases of genital herpes are estimated each year in the USA [2] and more than 20 000 cases are reported from STD clinics in the UK [3]. Data taken from ten developed countries show that 107 million people are herpes simplex virus type 2 (HSV 2) seropositive [4]. HSV 2 infection, which is mainly responsible for genital herpes, has increased worldwide [5]. A recently published report by Fleming et al. showed that every fifth person in the USA older than 12 years is carrying HSV 2 [6]. The HSV 2 seroprevalence has increased by 30% between 1976 and 1994. This affected increase particularly white teenagers [6]. This is surprising, because at the same time intensive HIV-prevention campaigns were performed in the USA. The special features of genital HSV infection which make therapy so vital are that it is carried lifelong and patients may suffer from many recurrences. Fortunately primary disease affects only 1% of those who get infected. Primary herpes is a severe outbreak of disseminated vesicular lesions accompanied by local swelling, discharge and altogether more serious symptoms than those of recurrent disease. However, recurrences with minor symptoms continually affect people and cause distress and psychosocial problems. In addition stable partnerships may be jeopardized and quality of life reduced. The list of complications and risks of genital HSV infection make efficacious therapy highly desirable. This applies particularly to persistent genital erosions and ulcers that make transmission and acquisition of HIV a lot easier [7–9]. In the case of genital herpes during pregnancy, different modes of management are being used. It is important to consider systemic antiviral therapy for the mother and for the benefit of the unborn child, for whom HSV may be dangerous and even life-threatening [10]. It is common knowledge that current systemic antiviral therapies alleviate symptomatic genital herpes and act prophylactically when long term therapy is continued. Treatment with acyclovir is safe according to several studies of long term treatment of persons with recurrent genital herpes [11,12]. Recently, moreover, antiviral therapy of genital herpes has been considerably improved. Valaciclovir, the valylester of acyclovir if given orally, has the same antiviral activity as acyclovir, but has the potential for less frequent administration because of its superior pharmacokinetics [13,14]. Both first-episodes and recurrences are best treated by twice daily oral administration of 500 mg valaciclovir for 5 days. Suppressive therapy is one tablet daily during the first year, in cases with frequent recurrences (history of six to eight genital herpes recurrences per year). Intravenous acyclovir should be reserved for severe first-episode or primary genital herpes. Another compound developed for herpesvirus infections and also successfully used for genital herpes is famciclovir, the diacetylester of penciclovir. Famciclovir acts similarly to acyclovir and valaciclovir. Its efficacy in genital herpes is comparable. There is also better biovailability of famciclovir in comparison to acyclovir which allows a less frequent and more convenient dosing schedule. Dosing three times daily is necessary for first-episode and recurrent disease. Suppressive therapy requires two oral administrations per day [15]. A recently published observation in mice suggests that * Tel.: +49-381-4949701; fax: +49-381-4949702.

Ability of a rapid serology test to detect seroconversion to herpes simplex virus type 2 glycoprotein G soon after infection.

Sera (n = 188) from 29 patients with first-episode genital herpes simplex virus type 2 (HSV-2) infections were tested by POCkit-HSV-2 and Western blot (WB) to determine the speed of seroconversion. The median time to detection of HSV-2 antibody was 13 days (range, 3 to 102 days) by the POCkit-HSV-2 test versus 13 days (range, 2 to 58 days) for WB.

New developments in the epidemiology, natural history and management of genital herpes

The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.

Clinical course of patients with serologic evidence of recurrent genital herpes presenting with signs and symptoms of first episode disease.

The care of patients with first episode and recurrent genital herpes differs with respect to therapy and source partner evaluation. Of 498 persons who presented with what appeared by history and symptoms to be a first episode of genital herpes, we identified 41 who had serologic evidence of remotely acquired herpes simplex virus 2 (HSV-2) infection. To define the natural history of these individuals with previously unrecognized HSV-2 and to evaluate if any clinical or historical features could differentiate these people from persons with true first episode infection. Observational cohort study. Clinical overlap existed in the frequency of local symptoms, fever, and size of genital lesions between those with remotely acquired versus recently acquired genital herpes. The frequency of new sexual partners and recent sexual history were also similar in the two groups. However, on follow-up, the lesions of persons with remotely acquired HSV-2 healed more rapidly and subsequently recurred less frequently than those of true primary HSV-2. Even in a referral clinic with experienced clinicians, almost 10% of persons who are judged to have first episode genital herpes have evidence of remotely acquired HSV-2, suggesting that clinical differentiation of first episode genital herpes from previously acquired infection is difficult. Type-specific serologic testing assists the clinician in correctly classifying the infection and determining the potential source partner.

Treatment of Genital Herpes in Males with Imiquimod 1% Cream

The aim of this randomised, double-blind, placebo-controlled study was to examine the clinical significance, efficacy and tolerability of imiquimod 1% cream to manage patients exposed to first episodes of genital herpes. Male patients (n = 60), ranging in age between 18 and 50 years (mean 25.7 years), presenting for <6 days (mean 4.4 days) with culture-confirmed diagnosis of genital herpes, and bearing a total of 696 lesions (mean 11.6 lesions/ patient), entered the study and were randomised to receive a precoded 40g tube and instructions on how to apply the trial medication to their lesions twice for 5 consecutive days per week. A marked clinical benefit from self-application of imiquimod 1% cream was demonstrated, resulting in both significantly shorter mean duration of healing than with the placebo (5.2 vs 14 days; p < 0.001) and more healed patients [23 of 30 (76.7%) vs 2 of 30 (6.7%); p < 0.0001]. Of the 60 patients, 54 (90%) reported no drug-related adverse effects. Two patients in the imiquimod group reported non-objective mild burning sensation and four experienced a transitory increase in their body temperature (>38 degrees C) accompanied by mild headache and malaise; however, such indications were not severe enough to cause discontinuation of the treatment, and resolved within 24 hours. Treatment was well tolerated by all the patients, with no dropouts. Among 25 healed patients, four had a relapse after 9 months. Although the analogue of imiquimod 1% cream demonstrated mild to moderate subjective adverse effects, it was significantly more effective than placebo in treating patients with a first episode of genital herpes. Further clinical studies appear warranted.