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Abstract
Herpes simplex virus infections are transmitted through contact with infected oral or genital secretions. The virus can be present on mucosa during a symptomatic recurrence or asymptomatically. Most transmissions to neonates and sexual partners occur during asymptomatic viral shedding. The frequency of viral isolation in the absence of lesions ranges from 2% to 6% of days; however, studies using more sensitive tests, such as polymerase chain reaction, show that viral shedding can occur on the average 28% of days.
... The outermost layer of the virion is an envelope constructed from the lipid bilayer, derived from the infected host cell. The surface of the envelope is covered with 10-12 glycoproteins (Wald, 1998). The penetration of both HSV-1 and HSV-2 into the host cell involves at least five viral envelope glycoproteins (gC, gB, gD, gH, gL), together with three classes of host cell membrane receptors (herpes virus entry mediator, nectin-1, nectin-2, and cell surface glycosaminoglycans, preferentially heparan sulfate) (Akhtar and Shukla, 2009;Wald, 1998). ...
... The surface of the envelope is covered with 10-12 glycoproteins (Wald, 1998). The penetration of both HSV-1 and HSV-2 into the host cell involves at least five viral envelope glycoproteins (gC, gB, gD, gH, gL), together with three classes of host cell membrane receptors (herpes virus entry mediator, nectin-1, nectin-2, and cell surface glycosaminoglycans, preferentially heparan sulfate) (Akhtar and Shukla, 2009;Wald, 1998). Heparan sulfate thus becomes a very attractive target to generate NPs able to block HSV interaction with the host cell surface. ...
... Therefore, we can assume that the antiviral activities of tannic acid-modified NPs are the effect of the combined activities of silver and tannic acid. The surface of HSV-2 is composed of glycoproteins with N-or O-linked sugars (Wald, 1998), which can readily interact with tannic acid moieties on the surface of NPs and help the nanosilver to interact with the virus envelope and destroy it (Fig. 12.12). By binding to virions, NPs also play a role of a physical obstacle, making virion-receptor interaction difficult ( Fig. 12.12). ...
Tannins are phenol derivatives naturally synthesized by plants as metabolic products. For centuries tannins have been used in medicine as agents supporting wound healing, due to their antiinflammatory and antimicrobial properties. Tannic acid is the most common and principal hydrolysable tannin. Here, we describe the method for synthesis of silver or gold copper/silver nanoparticles by chemical reduction method using tannic acid. This method allows for precise shape and size control of metallic nanoparticles having surface modified by tannic acid to increase attachment, antimicrobial and antiinflammatory properties. The interaction between nanoparticles and viruses is attracting great interest due to the need for new antivirals. We demonstrated that tannic acid modified silver nanoparticles are capable of reducing herpes simplex type 2 (HSV-2) infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver and silver/copper nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified AgNPs and Ag/CuNPs reduced both infection and inflammatory reaction in the mouse model of HSV infection. Therefore, tannic acid modified silver and silver copper alloy nanoparticles consist good candidates for microbicides used in treatment of infections with enveloped viruses, such as herpes viruses.
... The significance of latency is that it is a reservoir of infection that can periodically reactivate, causing virus to travel down nerve fibers to skin or mucous membranes in the dermatome of primary infection. This may be manifest clinically as recurrent GH or more frequently, causes unrecognized shedding of infectious HSV [4-7] which despite being unrecognized is responsible for the majority of new HSV-2 infections [8]. The epidemiology is further complicated by the fact that many primary infections are asymptomatic or unrecognized, which has the important implication that the first clinical presentation of GH, often referred to as the initial episode, may be caused by a recurrence of a prior asymptomatic primary infection [9]. ...
Background
Genital herpes (GH) is a recurrent sexually transmitted infection (STI) that causes significant morbidity and is also the major source of herpes simplex virus (HSV) in cases of neonatal herpes. Vaccination is a current goal which has had limited success so far in preventing GH and microbicides offer an attractive alternative. Treatment of primary disease cannot prevent establishment of latent infections and thus, cannot prevent subsequent recurrent disease. Recently, many of the molecular events leading to entry of HSV into cells have been elucidated, resulting in the description of a number of herpesvirus entry mediators (HVEMs) that interact with HSV glycoprotein D (gD) on the surface of virions. Described here is a strategy for interrupting the spread of HSV based on interfering with these interactions. The hypothesis addressed in the current report was that single chain antibody variable fragments (scFv) that interrupt associations between gD and HVEMs would not only prevent infection in vitro but could also be used as microbicides to interfere with acquisition GH.
Results and Conclusions
Here we show that a scFv derived from a particular hybridoma, DL11, not only inhibits infection in vitro but also prevents development of GH in a guinea pig model when applied intravaginally in an inert vehicle. Comparison of different anti-gD single chain antibodies supported the hypothesis that the activity of DL11-scFv is based on its ability to disrupt the associations between gD and the two major receptors for HSV, nectin-1 and HveA. Further, the results predict that bacterial expression of active single chain antibodies can be optimized to manufacture inexpensively a useful microbicidal product active against HSV.
Introduction: Little information is available regarding the specific sexual practices of lesbians, and whether these activities may carry an associated health risk. Methods: Self-identified lesbians from all U.S. states (N = 6935) responded to a questionnaire that was printed in a national biweekly gay, lesbian and bisexual news magazine. Items included sexual practices engaged in with women during the past 1 and 5 years, past history of a sexually transmitted disease (STD), number and gender of lifetime and recent sexual partners, concerns regarding STDs, and risk reduction behaviors. Results: Lesbians engaged in a variety of sexual activities with female partners including orogenital sex, use of a dildo, and anilingus. Seventeen percent reported a lifetime diagnosis of an STD. Women with a history of an STD were more likely to be concerned about STDs, to ask questions of their new female sexual partners, and to have had an HIV test. Conclusions: Lesbians participate in a variety of sexual activities with their female partners that involve the exchange of body fluids, potential exposure to blood, and genital and anal stimulation that may put them at risk for STDs.
For the primary infection of genital herpes, antiviral therapy with acyclovir is the gold standard. For recurrences, there are two options: antiviral treatment of each outbreak as it arises, or suppression of outbreaks with daily oral therapy. Patients tend to prefer the latter because it can decrease the number and severity of outbreaks, but it increases asymptomatic viral shedding and, therefore, the risk of unwittingly transmitting herpes simplex virus to uninfected sexual partners.
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.
Neonatal herpes is a serious condition. The objectives of this critical review of the literature are to: 1) define the modes of mother-infant and indirect transmission of HSV infection; 2) determine current treatments and perspectives for the future.
We searched for articles published since 1980 in databases using a series of key words. The articles were classed into three categories by level of scientific proof: good (level 1), fair (level 2), poor (level 3, 4 or 5). General reviews were excluded.
We selected 153 articles and retained 96. Man to woman contamination was generally reported: 10p.100 of the couples were serodiscordant. Presence of anti-HSV1 antibodies was partially protective against HSV2 infection. Neonates can be contaminated in utero via transplacental hematogenic transmission, at delivery (the most frequent route), or during the postnatal period (indirect transmission). The risk of neonatal contamination is greatest for primary infection (PI) or non-primary infection occurring the last month of pregnancy (50p.100), but transmission is low for maternal recurrence during the week before delivery (5p.100). Cesarean section is mandatory in case of genital PI or non-primary maternal infection during the last month of pregnancy, especially in case of membrane rupture<6 hr, but does not protect the infant in two-thirds of the cases. The decision for cesarean is controversial in case of recurrence. Antiviral treatment of the mother using aciclovir (ACV) is well tolerated. ACV-cesarean combination provides maximal protection for the neonate. A neonate with proven or suspected HSV infection should be isolated from other neonates but not from the mother. Breastfeeding is contraindicated in case of breast lesions. Parenteral ACV 60 g/kg/d is preferred over vidarabine. It should be started immediately after the first virology samples. The risk of recurrence is estimated at 7p.100 for all neonates and warrants treatment using a high oral dose (90-100mg/kg/d) due to the low bioavailability, if the number of recurrences is>3 in 6 months. Antiviral treatment is formally indicated if: 1) neonate viral cultures are positive at day 1 and day 3, 2) clinical lesions suggest herpes, 3) neurological disorders or signs of sepsis with negative bacteriology are present and the mother has a history of herpes or contact with labial herpes; and can be discussed if: 4) PI is proven at delivery or during the last month of pregnancy (irrespective of the delivery route, even if the mother is treated or if the membranes are intact), 5) late cesarean (membrane rupture>4 h) with clinical herpes at delivery, 6) vaginal delivery and recurrent herpes within the last month with associated clinical risk factor(s).
Many points remain to be clarified concerning optimal management of the mother-infant couple in case of maternal herpes during pregnancy or at delivery. New perspectives concerning diagnosis and prevention of neonatal contamination include: identification of asymptomatic primary infections using rapid identification of genital viral antigen during delivery, identification of women with a risk of asymptomatic excretion using specific serology tests for the pregnant woman and her partner, antiviral treatment for men, topical genital treatments, vaccination of women at risk, monoclonal antibodies, new antiviral agents with mechanisms of action independent of viral thymidine kinase.
A European panel of physicians reviewed the current treatments and perceptions of recurrent genital herpes (GH) across the continent. The panel consisted of specialists in dermatology and venereology from France, Finland, Germany, Italy, Norway, Spain, Sweden and the UK. A wide variety of factors that influence GH management were considered, including different health delivery systems, funding and cultural differences. The poor awareness of GH among both the general public and physicians was highlighted. The effectiveness of GH management was then examined from a patient's viewpoint, including the confirmation of the diagnosis, information and counselling about GH, as well as prescriptions for treatment. It was agreed that both physicians and patients often feel uncomfortable about discussing the disease, and that a European-wide effort is needed to re-educate patients and physicians about GH. The panel identified clear and unmet needs to manage a patient with clinical recurrences and to attempt to reduce the risk of GH transmission. Finally, resiquimod, an immune response modifier, was considered as a potential treatment option for GH.
To present to general dentists the typical signs and symptoms associated with adult acute (primary) herpetic gingivostomatitis. The pertinent laboratory tests, management options and current pharmacotherapy are also reviewed. REVIEW DESIGN: The clinical files of 13 adult patients were reviewed. All had no history of herpes simplex virus infection and presented with oral lesions suggestive of primary herpetic infection. The subjects were all patients of one of the investigators, and their workup included Tzanck testing and viral culture.
The patients ranged in age from 18 to 79 (mean 37.2, standard deviation 19.6) years. Nine (69%) were men. Viral culture was confirmed as the gold standard for diagnosis. The sensitivity of Tzanck testing was 77% (10/13), slightly higher than that reported previously (40% to 50%). In this patient group the febrile lymphadenopathic profile was typical of younger patients (18 to 42 years of age), whereas older patients presented with predominantly oral symptoms.
Primary herpetic gingivostomatitis is not limited to children but can affect people of any age. Proper diagnosis and treatment are essential, particularly in elderly and immunocompromised patients. Tzanck testing may serve as a useful adjunct in diagnosis. Antiviral agents such as valacyclovir and famciclovir should be considered part of early management. Dentists are often the first health care professionals to be consulted by patients with this condition, and recognition of the infection is paramount.
The scope of gynecologic infections presenting to the emergency department is quite diverse. This article presents an update on the current literature for vaginitis, cervicitis, pelvic inflammatory disease, tubo-ovarian abscesses, the Fitz-Hugh-Curtis syndrome, herpes, and syphilis. Inadequate identification or treatment of these diseases can result is significant morbidity or mortality for the patient and for the fetus.
This review considers the epidemiology and impact of genital herpes, discusses how herpes simplex virus-2 (HSV-2) is transmitted, and reviews data on methods of reducing the risk of HSV transmission.
Information for the paper was identified through multiple PubMed searches. Information in the section on interventions was identified through PubMed searches using several pairs of key words (herpes and transmission, herpes and treatment, herpes and antiviral, herpes and valacyclovir, herpes and famciclovir, herpes and acyclovir, herpes and condom, herpes and clinical trial). The searches, conducted in January 2005, did not have date limits. Papers were selected for inclusion based on the author's judgment of their relevance to the topic of the review.
An estimated 45 million persons in the United States have genital herpes infection, and new infections occur at a rate of approximately one million per year. Approximately 85% to 90% of infections are unrecognized and therefore undiagnosed. Individuals with genital HSV-2 infection shed virus during asymptomatic periods as well as symptomatic periods. In fact, transmission frequently occurs during periods of asymptomatic viral shedding. Asymptomatic viral shedding (1) occurs in the majority of patients with genital HSV-2 infection; (2) accounts for approximately one third of the days of viral shedding; (3) occurs regardless of duration of infection but is most frequent during the first year after infection; (4) occurs more than 7 days before or after a symptomatic recurrence 50% of the time; and (5) does not differ significantly when comparing patients with 1 to 12 annual recurrences to those with no recurrences. A recently published study of discordant couples counseled on safe sex practices found that once daily suppressive therapy with valacyclovir reduced the risk of transmission of HSV-2 in heterosexual immunocompetent adult couples discordant for HSV-2 infection. In an 8-month study, daily valacyclovir compared with placebo reduced the risk of acquisition of symptomatic genital HSV-2 infection by 75% (2.2% placebo vs. 0.5% valacyclovir; hazard ratio = 0.25; p = 0.008). The overall risk of acquisition of HSV-2 infection (defined via laboratory-confirmed symptoms or seroconversion) was reduced by 48% (3.6% placebo vs. 1.9% valacyclovir hazard ratio = 0.52; p = 0.04). The most common adverse events in the study were headache, nasopharyngitis, and upper respiratory infection.
Daily suppressive therapy is recommended as a therapeutic option for HSV-2 seropositive individuals at risk of transmitting HSV-2. Because no intervention completely protects against transmission of HSV, infected individuals and their partners should be counseled to use safer sex practices, including the use of condoms.
Herpes simplex virus (HSV) infections are among the most common infectious diseases in humans. The prevalence of herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) varies widely across the world. HSV-2 infection is the primary cause of genital herpes. It is highly prevalent in human populations in many parts of the world, and is the most common cause of genital ulcer disease worldwide. In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few data have been published regarding the seroprevalence of herpes simplex infection, while no data exist regarding the Turkish population.
We aimed to investigate the prevalence of HSV-1 and HSV-2 in selected populations in Turkey. A cross-sectional study was conducted involving 2082 serum samples of 725 adults, 300 pregnant women, 200 blood donors, 483 sex workers and 110 patients with genital warts and 264 hotel staff in Istanbul, Turkey. All serum samples were assessed for HSV1 and HSV-2 IgG antibodies using an HSV-type specific, enzyme-linked immunosorbent assay (ELISA).
The prevalence of HSV-2 and HSV-1 antibodies was 4.8 and 85.3% in sexually active adults; 5.5 and 96% in blood donors; 5 and 98% in pregnant women, 17.3 and 93.6% in patients with genital warts; 8.3 and 97.3% in hotel staff; and 60% and 99% in sex workers.
These results confirm a higher prevalence of HSV infection than estimated, especially in high risk groups in Turkey. The high prevalence of HSV infection underlines the need for education among these populations.
A wireless network consists of a large number of nodes that use wireless communication links to collectively perform certain tasks in various application domains (industry, military, etc.). Since wireless nodes are irregularly scattered over a large application area, a suitable wireless multihop routing protocol is needed to facilitate the communication between arbitrary nodes. Many geographic routing protocols use a planar graph as the underlying network topology. This paper presents an efficient algorithm for the localized computation of such an underlay, namely, the short Delaunay triangulation (SDT). The SDT contains all edges of the Delaunay triangulation that are shorter than the communication range. The great asset of the short Delaunay triangulation is its spanning property: It approximates the shortest path of the unit disk graph by a constant factor. Our distributed algorithm for constructing the SDT surpasses alternative underlay construction algorithms and requires point-to-point communication links only.
Herpes simplex virus type 2 (HSV-2) infection is usually transmitted sexually and can cause recurrent, painful genital ulcers. In neonates the infection is potentially lethal. We investigated the seroprevalence and correlates of HSV-2 infection in the United States and identified changes in HSV-2 seroprevalence since the late 1970s.
Serum samples and questionnaire data were collected during the National Health and Nutrition Examination Surveys (NHANES) II (1976 to 1980) and III (1988 to 1994). HSV-2 antibody was assessed with an immunodot assay specific for glycoprotein gG-2 of HSV-2.
From 1988 to 1994, the seroprevalence of HSV-2 in persons 12 years of age or older in the United States was 21.9 percent (95 percent confidence interval, 20.2 to 23.6 percent), corresponding to 45 million infected people in the noninstitutionalized civilian population. The seroprevalence was higher among women (25.6 percent) than men (17.8 percent) and higher among blacks (45.9 percent) than whites (17.6 percent). Less than 10 percent of all those who were seropositive reported a history of genital herpes infection. In a multivariate model, the independent predictors of HSV-2 seropositivity were female sex, black race or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. As compared with the period from 1976 to 1980, the age-adjusted seroprevalence of HSV-2 rose 30 percent (95 percent confidence interval, 15.8 to 45.8 percent). The seroprevalence quintupled among white teenagers and doubled among whites in their twenties. Among blacks and older whites, the increases were smaller.
Since the late 1970s, the prevalence of HSV-2 infection has increased by 30 percent, and HSV-2 is now detectable in roughly one of five persons 12 years of age or older nationwide. Improvements in the prevention of HSV-2 infection are needed, particularly since genital ulcers may facilitate the transmission of the human immunodeficiency virus.
Objective:
To determine the frequency of asymptomatic perianal shedding of herpes simplex virus (HSV) in adult patients with acquired immunodeficiency syndrome (AIDS).Design:
Cross-sectional study.Setting:
A 1000-bed, state-supported hospital in Brazil that provides comprehensive health care.Patients:
Eighty-two consecutively hospitalized patients with AIDS (Centers for Disease Control and Prevention class C).Main Outcome Measurement:
Specimens for HSV culture were obtained with premoistened swabs of the perianal region at approximately 7-day intervals during the hospitalization of each patient. After the specimens were inoculated into cultures of human foreskin and Vero cells, supernatants of cultures showing the cytopathic effect characteristic of HSV infection were tested for virus in a confirmatory immunoenzymatic assay. Typing of HSV was performed by polymerase chain reaction amplification of HSV-1- and HSV-2-specific DNA polymerase sequences.Results:
On entry into the study, 12 (15%) of 82 patients had perianal ulceration and 70 did not. None of the patients in the latter group developed perianal ulcers during the study period, but HSV was isolated at least once from 17 (24%) of them. Nine of the 17 asymptomatic perianal shedders had a mean of 3 perianal swabs collected before the first HSV isolation, and 11 (65%) of 17 had a total of 18 perianal swabs collected 8 to 62 days after the HSV isolation. All postpositive samples were negative for HSV except 1 obtained from a patient 13 days after the first positive sample. Twelve of the 17 asymptomatic perianal shedders of HSV were followed up clinically for 8 to 62 days after the first episode of shedding, and none developed perianal ulceration.Conclusions:
We conclude that asymptomatic perianal shedding of HSV is common in patients with AIDS, even among those without a history of perianal HSV lesions. This shedding appears to be short-lived, intermittent, and not associated with early subsequent development of perianal ulcers. These findings present a new perspective on the natural course of perianal HSV infection in patients with AIDS.Arch Dermatol. 1997;133:180-183
The aim of this prospective study is to determine if patients identified by history, clinical examination and serologic status as having asymptomatic herpes virus type 2 infection report clinically recognizable genital lesions after having a detailed instructional session on the clinical signs and symptoms of genital herpes
Obiective: 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
. Objective : To compare the prevalence of genital herpes simplex virus type 2 (HSV-2) shedding in human immunodeficiency virus (HIV)-seropositive women and HIV-seronegative women. . Design : Cross-sectional study . Setting : A major inner-city medical center. . Patients : 106 women who were HIV-seropositive and HSV-2-seropositive and 70 women who were HIV-seronegative and HSV-2-seropositive were enrolled from various primary care settings. . Measurements : Herpes simplex virus type 2 antibody determinations were done for all patients. Regardless of symptoms, vulvar and cervical HSV cultures were obtained from all HIV-seropositive women and from a randomly selected subgroup of HIV-seronegative women. . Results : The prevalence of HSV-2 shedding was nearly four times greater in HIV-seropositive than in HIV-seronegative women (13.2% compared with 3.6% ; P = 0.04 ; odds ratio, 4.1 [95% CI, 1.0 to 27.4]) when the serum antibody for HSV-2 was present. Seventy-nine percent of viral shedding among HIV-seropositive women was asymptomatic. Overall viral shedding increased significantly as the CD4 cell count decreased. . Conclusions : Women with HIV infection, particularly those with low CD4 cell counts, shed HSV-2 from the vulva and cervix more commonly than women not infected with HIV. Most of this shedding is asymptomatic.
Objective.
—To investigate the prevalence and level of genital herpes simplex virus (HSV) among women at delivery.Design, Patients, and Setting.
—A prospective analysis of HSV by culture and by polymerase chain reaction (PCR) of genital specimens and by HSV serologic studies in 100 asymptomatic women in labor; prospective analysis of HSV by PCR among 50 seronegative nonpregnant women at a student health center; and retrospective analysis of genital specimens for HSV by PCR from 17 HSV culture-positive women with uninfected neonates and from two HSV culture-negative women with HSV-infected neonates. All pregnant women were at a university hospital.Main Outcome Measures.
—Presence of HSV by culture and levels of HSV by quantitative, type-specific PCR in cervical and vulvar specimens; HSV serologic testing by Western blot.Results.
—All of the 100 asymptomatic women in labor who were studied prospectively were HSV culture negative. In nine HSV was recovered by PCR. Herpes simplex virus was recovered by PCR in one of the 50 seronegative nonpregnant women; she soon became seropositive. All 17 culture-positive women had HSV recovered by PCR. High levels of HSV DNA were obtained by PCR from the two culture-negative women with infected neonates. Among those from whom HSV was recovered by PCR, HSV DNA levels were 250 times higher from culture-positive samples than from culture-negative samples (11 571 genome equivalents vs 46 genome equivalents; P<.001).Conclusions.
—The frequency of infant exposure to HSV DNA—containing secretions from HSV-seropositive mothers is about eight times higher than previously reported using HSV culture methods. High maternal levels of HSV DNA may be associated with an increased frequency of transmission of HSV to the infant.(JAMA. 1994;272:792-796)
Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.
(JAMA. 1990;263:418-420)
Objective : To assess the effect of the antiviral drug acyclovir on the frequency of subclinical shedding of herpes simplex virus (HSV) in the genital tract. Design : A double-blind, placebo-controlled, crossover clinical trial. Setting : A university-based virology research clinic. Patients : 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. Intervention : Participants were randomly assigned to receive either acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period, and then placebo for 70 days, or the study medications in the reverse order. Measurements : Women collected daily genital swabs of the vulvar, cervicovaginal, and perianal areas for HSV culture, maintained a diary of genital lesions, and were examined at the time of recurrences. Results : In an intent-to-treat analysis of the initial treatment period, 15 of the 17 women who received placebo and 3 of the 17 women who received acyclovir had at least 1 day of subclinical shedding (P < 0.001). Among the participants who received placebo, subclinical shedding occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the participants who received acyclovir (P < 0.001). The relative risk for subclinical shedding was 0.09 (95% Cl, 0.03 to 0.35) for the women who received acyclovir compared with the women who received placebo. In a paired analysis of 26 women who completed both arms of the study, acyclovir therapy was associated with a decrease in the frequency of subclinical shedding ; subclinical shedding occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days with acyclovir (P < 0.001)-a 94% reduction. The frequency of subclinical shedding was reduced at all anatomic sites and in all patients. Conclusions : Daily therapy with oral acyclovir suppresses subclinical shedding of HSV-2 in the genital tract, suggesting that studies to evaluate the use of acyclovir in preventing HSV-2 transmission are warranted.
▪ 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.
To determine the risk of sexual transmission of genital herpes simplex virus (HSV) in heterosexual couples.
Prospective study of couples who were participants in a clinical trial. Each source partner had symptomatic, recurrent genital HSV, and each susceptible partner was without serologic or clinical evidence of genital herpes. Couples were followed for a median of 334 days.
Two university-based research clinics.
One hundred forty-four heterosexual couples were studied out of an initial enrollment of 214 couples.
Development of culture-proven HSV infection or type-specific antibodies in the susceptible partner.
Transmission occurred in 14 (9.7%) couples, including 11 (16.9%) of 65 couples with male and 3 (3.8%) of 79 with female source partners (P = 0.05). The annual rate of acquisition was higher (31.8%) in susceptible female partners who lacked antibodies to either HSV type 1 or 2 at entry compared with females with HSV type 1 antibodies at entry (9.1%). Couples avoiding transmission of HSV reported fewer days with genital lesions in source partners. Detailed histories were available at the time of transmission in 13 couples. In nine couples, transmission occurred when the source partner was reported to be asymptomatic and in four, it resulted from sexual contact at the time of prodrome (1 case) or within hours before lesions were first noticed by the source partner (3 cases).
Despite clear recognition of genital herpes in source partners, there was substantial risk for transmission; in 70% of patients, transmission appeared to result from sexual contact during periods of asymptomatic viral shedding. The risk for acquisition of HSV was higher in women than men, and previous HSV type 1 infection appeared to reduce the risk for acquisition of HSV type 2 infection among women.
The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown.
We performed physical examinations, colposcopy, Pap smears, viral cultures, and HSV type-specific serologic assays of 779 randomly selected women attending a sexually transmitted disease clinic.
Evidence of HSV type 2 infection was detected in 363 women (47 percent), and 9 others (1 percent) had positive cultures indicative of urogenital or anal infection with HSV type 1. Of these 372 women, only 82 (22 percent) had symptoms. Fourteen women (4 percent) had viral shedding without symptoms, 60 (16 percent) had formerly had symptomatic episodes, and 216 (58 percent) had antibodies to HSV-2 with neither viral shedding nor a history of clinical episodes. Characteristic ulcerations of the external genitalia were present in only two thirds of the 66 women with positive HSV cultures; the others had atypical genital lesions or asymptomatic viral shedding. Isolation of HSV from a genitourinary tract specimen was the most sensitive (77 percent) test for confirming a first episode of infection. The detection of HSV-2-specific antibodies was the most sensitive (97 percent) way to confirm symptomatic reactivations of HSV-2 infection. HSV-2 serologic testing also identified the 290 women with asymptomatic HSV-2 infections (37 percent), including 14 (5 percent) who were shedding virus asymptomatically on the day of the examination.
The current strategy for diagnosing genital HSV infection in women misses many cases. Newly developed type-specific serologic methods can identify women with recurrent genital HSV-2 infection, as well as those with unrecognized or subclinical infection.
In this review we summarize current knowledge related to the identification of pregnancies that may be complicated by genital
herpes and describe the consequences of maternal infections with genital herpes. We address the implications of this information
for the management of genital herpes during pregnancy and at delivery and for the care of neonates exposed to herpes simplex
virus at delivery. On the basis of the current data, we cannot make specific recommendations concerning many of the clinical
problems that are caused by herpes simplex virus infections in pregnant women. We identify and discuss unresolved questions
about optimal management.
To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with
reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four
episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the
lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of
viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes,
and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus
3 of 17 days by viral isolation (P < .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure
of HSV infection than routine viral culture and that PCR detects the presence ofHSV at times when culture is negative.
To define the risk factors associated with neonatal acquisition of herpes simplex virus (HSV) infection, we prospectively obtained HSV cultures from the cervix and external genitalia of 15,923 pregnant women in early labor who were without symptoms or signs of genital HSV infection. Follow-up of the women with positive cultures for HSV and their HSV-exposed infants included serologic tests and serial cultures for HSV.
HSV was isolated from 56 of the women (0.35 percent), 18 of whom (35 percent) had serologic evidence of a recently acquired, subclinical first episode of genital HSV infection, and 34 of whom (65 percent) had reactivation of HSV. Neonatal HSV developed in 6 of 18 infants (33 percent) born to the women with a first episode of genital HSV, and in 1 of 34 infants (3 percent) born to the women with reactivation of HSV (P less than 0.01); neonatal HSV also occurred in three of the infants born to the 15,867 women with negative cultures. Neonatal HSV-2 occurred in 1 of 4 infants born to mothers seronegative at delivery for both HSV-1 and HSV-2, in 4 of 12 infants exposed to HSV-2 whose mothers had only HSV-1 antibodies at delivery, and in none of the infants born to 31 women who were HSV-2-seropositive. An increased risk of neonatal HSV was associated with exposure to viral shedding from the cervix and the use of fetal-scalp electrodes.
Of the asymptomatic women who shed HSV in early labor, about a third have recently acquired genital HSV, and their infants are 10 times more likely to have neonatal HSV than those of women with asymptomatic reactivation of HSV. The presence of maternal antibodies specific to HSV-2 but not HSV-1 appears to reduce the neonatal transmission of HSV-2. Further studies are necessary to determine whether screening and prophylactic treatment are warranted for infants of HSV-2-seronegative mothers who shed HSV-1 or HSV-2 in early labor.
Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.
To evaluate the prevalence of symptomatic versus asymptomatic or unrecognized type 2 herpes simplex virus (HSV-2) infection, the authors performed physical examination, viral cultures, and type-specific serologic assays in 776 randomly selected women attending an STD clinic and 636 female university students. Forty-six percent of women attending the STD clinic compared with 8.8% of the university students had serologic evidence of HSV-2 infection. Clinical or historical evidence of genital herpes was present in only 34% of the HSV-2 seropositive women attending the STD clinic and in 29% of the HSV-2 seropositive women attending the university clinic. Among women attending the STD clinic, the prevalence of recognized genital infection was more common among those with HSV-2 antibodies only versus those with HSV-1 and -2 antibodies (odds ratio = 2.39; 95% confidence interval = 1.30-4.37), suggesting that HSV-1 infection reduces the likelihood of recognizing HSV-2 infection. In view of the high proportion of seropositive individuals with unrecognized HSV-2 infection in both high and low prevalence HSV-2 seropositive populations, newly developed HSV type-specific serologic methods should be evaluated for detecting carriers of HSV-2 infection and counseling these individuals about strategies for avoiding sexual and perinatal transmission of HSV-2.
The polymerase chain reaction was adapted to the amplification ofa herpes simplex virus (HSV) DNA sequence, common to HSV
types 1 and 2 (HSV-1, HSV-2). The amplified product was detectable by ethidium-bromide staining or Southern hybridization
of gels and by dot hybridization. The HSV polymerase chain reaction detected HSV DNA in samples obtained from eight patients
with genital lesions from which HSV-2 was isolated in tissue culture and from four patients with labial lesions from which
HSV-1 was isolated. The HSV polymerase chain reaction identified HSV in clinical specimens obtained from 11 women who had
asymptomatic genital HSV infections at delivery. None of 11 samples obtaided at delivery from women who had antibodies to
HSV-2, but whose delivery cultures were negative, were positive by polymerase chain reaction and no false-positive reactions
were obtained when the reaction mixture contained human cell DNA or varicella-zoster virus, cytomegalovirus, Epstein-Barr
virus, or human papillomavirus DNA.
Twenty-six men and women with recurrent genital herpes maintained diaries of their symptoms and signs of infection and submitted 6,515 self-collected cultures during a one-year study of acyclovir therapy. As compared with periods before or after treatment, the mean rates of experiencing symptoms or lesions, and of shedding virus were significantly lower during treatment. Acyclovir treatment reduced the rate of symptomatic shedding from 95 positive cultures to six per 1,000 cultures, but the rate of asymptomatic shedding remained relatively constant, averaging eight per 1,000 cultures. Among the isolates of herpes simplex virus studied, there was no differences in sensitivity to acyclovir between strains recovered on or off therapy or during symptomatic or asymptomatic recurrences. The endonuclease cleavage profiles of asymptomatically shed viruses were essentially the same as those of the symptomatically shed viruses from the same individual. Chronic acyclovir therapy significantly reduced the symptoms and signs of recurrent genital herpes but did not eliminate virus shedding, nor, therefore, the possibility of disease transmission.
To determine the risk of transmission of genital herpes simplex virus (HSV) infection, we prospectively studied, for a median
of six months, 38 couples who had been together for a median of 10 mo. In each couple, one partner had a history of symptomatic
genital herpes and one did not. At entry, of the 38 asymptomatic, exposed partners, 21 were seronegative, and results of western
blot analysis showed that seven had antibody to HSV type 1 (HSV-1), four to HSV type 2 (HSV-2), and six to both HSV-1 and
HSV-2. One of the 28 exposed partners without antibody to HSV-2 at enrollment asymptomatically acquired HSV-2 infection, but
four of 10 with antibody to HSV-2 at enrollment developed culture-proven HSV-2 infection during follow-up. Restriction endonuclease
analysis of DNA from paired isolates revealed identical strains in three couples and different strains in one. In this group
of asymptomatic sex partners of persons with genital herpes, asymptomatic and unrecognized acquisition of HSV-2 infection
was common, but more than half of the exposed partners remained free of HSV-2 infection after a median of 16 mo of sexual
contact.
Sixty-six source contacts of index patients with first-episode genital infection caused by herpes simplex virus (HSV) were evaluated for evidence of current or past HSV infections. Forty-three source contacts (65%) reported a history consistent with previous recurrent HSV infection or were experiencing a first episode of genital herpes when initially examined. However, 60% of these 43 contacts were not aware that they had transmissible HSV infection. Twenty-nine (67%) of the 43 individuals had had recent sexual contact with an index patient when lesions were present. All of the remaining 23 source contacts, who were without a history of symptoms consistent with HSV infection, had detectable neutralizing antibody to HSV; HSV type 2 was isolated from the cervix of two of these asymptomatic source contacts. Efforts to identify individuals with undiagnosed genital herpes and to instruct these individuals concerning the risk of disease transmission in the presence of lesions are needed if the rate of transmission is to be decreased; however, methods designed to decrease the rate of transmission by asymptomatic individuals must also be evaluated.
13 men with a history of recurrent genital herpes simplex virus type 2 (HSV-2) infection were followed daily for 4 weeks with samples taken from the urethra for virus isolation. Asymptomatic virus shedding occurred in 5 men who had 1 single positive isolation each. Four of these urethral isolates were typed as HSV-1 and 1 as HSV-2.
We compared the clinical presentation of 95 newborns with herpes simplex virus (HSV) infection from 1973 through 1981 (first
period) with data from 196 newborns evaluated from 1982 through 1987(second period). There was a significant change in the
presentation of infection in these infants. From the first to the second period, the frequency of disseminated disease decreased
from 50.5% to 22.9%, whereas the frequency of skin, eye, and mouth (SEM) diseases increased from 17.9% to 43.4% (P < .001). The frequency of infants with central nervous system (CNS) disease remained relatively unchanged - 31.6% versus
33.7%. We also compared the demographic and clinical characteristics of the infants and their mothers. For neonates with CNS
or disseminated infection, disease duration and frequency of prematurity were significantly decreased in the second period,
as was the frequency of skin vesicles for newborns with SEM or disseminated infection. These changes are most likely the consequence
of recognizing and treating SEM infection before its progression to more-severe disease.
To assess the effect of the antiviral drug acyclovir on the frequency of subclinical shedding of herpes simplex virus (HSV) in the genital tract.
A double-blind, placebo-controlled, crossover clinical trial.
A university-based virology research clinic.
34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration.
Participants were randomly assigned to receive either acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period, and then placebo for 70 days, or the study medications in the reverse order.
Women collected daily genital swabs of the vulvar, cervicovaginal, and perianal areas for HSV culture, maintained a diary of genital lesions, and were examined at the time of recurrences.
In an intent-to-treat analysis of the initial treatment period, 15 of the 17 women who received placebo and 3 of the 17 women who received acyclovir had at least 1 day of subclinical shedding (P < 0.001). Among the participants who received placebo, subclinical shedding occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the participants who received acyclovir (P < 0.001). The relative risk for subclinical shedding was 0.09 (95% CI, 0.03 to 0.35) for the women who received acyclovir compared with the women who received placebo. In a paired analysis of 26 women who completed both arms of the study, acyclovir therapy was associated with a decrease in the frequency of subclinical shedding; subclinical shedding occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days with acyclovir (P < 0.001)--a 94% reduction. The frequency of subclinical shedding was reduced at all anatomic sites and in all patients.
Daily therapy with oral acyclovir suppresses subclinical shedding of HSV-2 in the genital tract, suggesting that studies to evaluate the use of acyclovir in preventing HSV-2 transmission are warranted.
The frequency, pattern, and anatomical sites of subclinical shedding of herpes simplex virus (HSV) in the genital tract, along with factors that predict such shedding, have not been well characterized.
We studied prospectively the clinical and virologic course of genital herpes in 110 women. The women kept symptom diaries and provided daily samples from the vulva, cervix, and rectum for viral culture.
During a median follow-up of 105 days, subclinical shedding of virus was identified in 36 of 65 women (55 percent) with HSV type 2 (HSV-2), in 16 of 31 women (52 percent) with HSV type 1 (HSV-1) and HSV-2, and in 4 of 14 women (29 percent) with only HSV-1. Among women with genital HSV-2 infection, subclinical shedding occurred on a mean of 2 percent of the days. The mean duration of viral shedding during subclinical episodes was 1.5 days, as compared with 1.8 days during symptomatic episodes. HSV was isolated from several sites in the genital tract and rectum in 17 percent of subclinical episodes and 22 percent of symptomatic episodes. Half the episodes of subclinical shedding of HSV occurred within seven days of a symptomatic recurrence. The risk of subclinical shedding increased with the frequency of symptomatic recurrences. Subclinical shedding was more frequent among women with more than 12 recurrences per year than among those with no symptomatic recurrences (odds ratio, 3.3; 95 percent confidence interval, 1.4 to 7.9); it was also more frequent among women who had recently acquired genital herpes (odds ratio for women with HSV acquired in the past year as compared with those who had had the infection for a year or more, 1.85; 95 percent confidence interval, 1.1 to 3.1).
Among women with a history of genital herpes infection, subclinical shedding of HSV is common and accounts for nearly one third of the total days of reactivation of HSV infection in the genital tract. Women with frequent symptomatic recurrences also have frequent subclinical shedding and may be at high risk for transmitting HSV.
This retrospective study was undertaken to evaluate the prevalence of the viral types and temporal epidemiology in patients with ano-genital herpes between 1983-92. One thousand one hundred and thirty-five patients with anogenital herpes were available for analysis. The annual incidence of anogenital herpes nearly tripled over the period of 7 years (1986-92) from 59 to 171 cases. The percentage of HSV-1 infection in female cases (63-79%) was much higher than in other reported studies and remained relatively constant over the study period.
The changing epidemiology of genital herpes in Edinburgh is described in relation to herpes simplex virus (HSV) Type 1 and herpes simplex virus Type 2 infection over a period of 14 years.
2018 episodes of genital herpes in 1794 patients over a 14 year period were assessed. Data on age, sex, sexual orientation, geographical origin and herpes antibodies were also analysed.
The proportion of cases that were HSV Type 1 increased over the period from approximately 20% to over 40%. Type 1 infection is more common in the young, in women and as a primary infection.
HSV Type 1 is of increasing importance as a cause of genital herpes in our population. This may reflect changes in sexual attitudes and practises over the past decade.
In a prospective study of factors associated with genital herpes simplex virus (HSV) type 2 transmission in couples in whom
1 partner had clinical genital HSV and the other did not, 11 (19%) of the 57 history-negative partners had HSV-2 antibody
by Western blot at entry. In follow-up (mean, 16 months) of29 HSV-2-seronegative partners, overall 4 (14%) seroconverted compared
with 3 (23%) of 13 HSV-1- and -2-seronegative partners and 1 (6%) of 16 HSV-1-seropositive partners. Since all seroconverters
were women, the risk of transmission may be higher in HSV-seronegative women. No significant differences were found between
HSV-2-seronegative partners and seroconverters regarding duration of relationships, number of partner recurrences, intercourse
frequency, or contraceptive method. However, 2 seroconverters were exposed to lesions without barrier contraception. This
study suggests that infection is commonly asymptomatic and that although the overall risk of genital HSV transmission in couples
is low (10%/ year), the risk may be significantly increased in women and in seronegative individuals.
Monoclonal antibody blocking radioimmunoassays (MAb block RIAs) which detect specific humoral responses to each of the two human herpes simplex virus (HSV) types are described. RIAs were compared with Western blot assay (WBA) in a blind study of 64 sera obtained from clinically well-documented cases of genital herpes. WBA and MAb block RIA each detected HSV-1 antibodies in 16/17 (94%) sera from confirmed HSV-1 genital infections (first episodes and recurrent infections). Detection of HSV-2 antibody in 21 sera from HSV-2 first episodes was more effective by WBA which identified homologous antibody in 19 (96%), whereas MAb block RIA detected HSV-2 antibody in 16 (76%). HSV-2 antibody was detected in 24/25 (96%) sera from recurrent HSV-2 infections by WBA and by MAb block RIA, the highest degree of concordance for both methods. In addition, the MAb block RIA may be more effective in detecting the presence of HSV-1 antibody in sera from recurrent HSV-2 cases. Prevalence of HSV-1 and HSV-2 antibody was measured by the MAb block RIAs in 3 UK human study populations which consisted of 100 children/young adolescents, 104 adult blood donors and 80 genito-urinary medicine clinic attenders.
To determine the frequency of asymptomatic perianal shedding of herpes simplex virus (HSV) in adult patients with acquired immunodeficiency syndrome (AIDS).
Cross-sectional study.
A 1000-bed, state-supported hospital in Brazil that provides comprehensive health care.
Eighty-two consecutively hospitalized patients with AIDS (Centers for Disease Control and Prevention class C).
Specimens for HSV culture were obtained with premoistened swabs of the perianal region at approximately 7-day intervals during the hospitalization of each patient. After the specimens were inoculated into cultures of human foreskin and Vero cells, supernatants of cultures showing the cytopathic effect characteristic of HSV infection were tested for virus in a confirmatory immunoenzymatic assay. Typing of HSV was performed by polymerase chain reaction amplification of HSV-1- and HSV-2-specific DNA polymerase sequences.
On early into the study, 12 (15%) of 82 patients had perianal ulceration and 70 did not. None of the patients in the latter group developed perianal ulcers during the study period, but HSV was isolated at least once from 17 (24%) of them. Nine of the 17 asymptomatic perianal shedders had a mean of 3 perianal swabs collected before the first HSV isolation, and 11 (65%) of 17 had a total of 18 perianal swabs collected 8 to 62 days after the HSV isolation. All postpositive samples were negative for HSV except 1 obtained from a patient 13 days after the first positive sample. Twelve of the 17 asymptomatic perianal shedders of HSV were followed up clinically for 8 to 62 days after the first episode of shedding and none developed perianal ulceration.
We conclude that asymptomatic perianal shedding of HSV is common in patients with AIDS, even among those without a history of perianal HSV lesions. This shedding appears to be short-lived, intermittent, and not associated with early subsequent development of perianal ulcers. These findings present a new perspective on the natural course of perianal HSV infection in patients with AIDS.
Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.
The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied.
We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections.
Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died.
Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.
Herpes simplex virus (HSV) infection is one of the most common opportunistic infections in HIV-infected persons. However, most documentation of the effectiveness of antiviral therapy in reducing HSV reactivation is anecdotal.
To evaluate the quantitative effect of antiviral therapy on the frequency of HSV reactivation in HIV-infected persons.
Double-blind, placebo-controlled, crossover trial.
Research clinic at a university hospital.
48 persons (45 men and 3 women) who were HIV positive and HSV seropositive.
Patients were randomly assigned to receive famciclovir, 500 mg orally twice daily, or placebo for 8 weeks. They then crossed over to receive the other regimen after a 1-week washout period.
Patients obtained daily cultures of their perirectal, urethral, oral, and genital areas and kept dairy records of signs and symptoms of genital and oral-labial herpes.
The median CD4 cell count at study entry was 384 cells/mm3. In the intention-to-treat analysis of the first study period, HSV was isolated on 122 of 1114 (11%) placebo days compared with 9 of 1071 (1%) famciclovir days (relative risk, 0.15; P < 0.001). For patients who completed the crossover, the median difference in days with symptoms between placebo and famciclovir was 13.8% of days and the median difference in days on which HSV was isolated was 5.4% of days (P < 0.001 for both). Percentage of days with HSV-2 shedding was reduced from 9.7% to 1.3%. Breakthrough reactivations that occurred while patients were receiving famciclovir were infrequent, short, and often asymptomatic, HSV-2 isolates from these reactivations were susceptible to penciclovir in vitro.
Antiviral chemotherapy with famciclovir results in clinically and statistically significant reductions in the symptoms associated with HSV infection and the symptomatic and asymptomatic shedding of HSV among HIV-positive persons.
Genital herpes is most often transmitted while the patient is asymptomatic, presumably during episodes of viral shedding.
To determine whether famciclovir is effective in reducing asymptomatic shedding, women with frequent, recurrent genital outbreaks
were enrolled in a randomized, double-blind, double-dummy, placebocontrolled, parallel-group, 112-day trial of suppressive
treatment with famciclovir for anogenital viral shedding. Sixty women received 125 mg of famciclovir 3 times daily, 59 received
250 mg of famciclovir 3 times daily, and 58 received placebo. Patients recorded symptoms and self-obtained cultures daily.
Famciclovir reduced asymptomatic shedding, compared with placebo (P < .0001). The onset of asymptomatic shedding was also delayed (P < .0001). Famciclovir reduced symptomatic shedding in a dose-dependent manner (0.72% for 125 mg 3 times daily vs. 0.19% for
250 mg 3 times daily [P < .0001] vs. 5.53% for placebo [P < .0001]). In conclusion, suppressive treatment with famciclovir reduced both asymptomatic and symptomatic viral shedding
and delayed the onset of asymptomatic shedding in women with frequently recurring genital herpes. Studies to examine the effects
of suppression by famciclovir on the transmission of genital herpes are warranted.
A double-blind, placebo-controlled trial of famciclovir for the suppression of clinical and subclinical HSV infection in HIV-infected persons
- Schacker
Frequent genital HSV-2 shedding in immunocompetent women
- Wald