Acquisition Of Herpes Simplex Virus Research Articles

Herpes simplex virus dissemination with necrotizing hepatitis following Descemet membrane endothelial keratoplasty

BackgroundCorneal transplants are the most common type of transplant and increasing in frequency. Donor cornea tissues are a rare source of herpes simplex virus (HSV) transmission and not routinely tested for presence of HSV. Donor graft-to-recipient transmission typically causes graft failure and anterior uveitis, and extra-ocular HSV disease has not been previously reported. We present a case of HSV transmission from donor cornea tissue that nearly cost the corneal transplant recipient his life.Case reportAn elderly immunocompetent man developed an acute illness 10 days after having donor corneal tissue implanted in a Descemet membrane endothelial keratoplasty (DMEK). He was found to have HSV necrotizing hepatitis per liver biopsy, trilineage cytopenia, rhabdomyolysis, acute kidney failure, altered mental status, early-stage hemophagocytic lymphohistiocytosis (HLH), and donor corneal tissue implant infection resulting in graft failure and anterior uveitis. HSV DNA was detected in cerebral spinal fluid, peripheral blood, explanted donor corneal tissue, and anterior chamber fluid (220 million HSV DNA copies per mL). HSV-1 seroconversion denoted a primary HSV infection, and the patient had no other risk factor for HSV acquisition. Early recognition of HSV dissemination prompting treatment with intravenous acyclovir, as well as a short course of HLH-directed therapy, resolved the systemic illness. Vision was restored to near normal by replacement of the infected corneal graft with new donor DMEK tissue in conjunction with intravitreal foscarnet treatment.ConclusionAwareness of the potential risk of donor cornea tissue transmitting HSV and leading to life-threatening HSV disease is paramount to early diagnosis and treatment. The role of donor cornea tissue in HSV transmission and disease merits additional attention and investigation.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Evolving Scalp Lesions in an 8-day-old Infant

Evolving Scalp Lesions in an 8-day-old Infant

Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques.

Herpes simplex virus 2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study host-HSV-2 interactions, an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333, and/or G) at a total dose of 1 × 107 PFU of HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA were consistently shed in vaginal swabs for the first 7 to 14 days after each inoculation. Proteins associated with wound healing, innate immunity, and inflammation were significantly increased in cervical secretions immediately after HSV-2 inoculation. There was histologic evidence of acute herpesvirus pathology, including acantholysis in the squamous epithelium and ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen in mucosal epithelial cells and keratinocytes. Further, an intense inflammatory infiltrate was found in the cervix and vulva. Evidence of latent infection and reactivation was demonstrated by the detection of spontaneous HSV-2 shedding post-acute inoculation (102 to 103 DNA copies/swab) in 80% of RM. Further, HSV-2 DNA was detected in ganglia in most necropsied animals. HSV-2-specifc T-cell responses were detected in all animals, although antibodies to HSV-2 were detected in only 30% of the animals. Thus, HSV-2 infection of RM recapitulates many of the key features of subclinical HSV-2 infection in women but seems to be more limited, as virus shedding was undetectable more than 40 days after the last virus inoculation.IMPORTANCE Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study of the initial molecular interactions of the two agents requires an animal model. We found that HSV-2 can infect RM after vaginal inoculation, establish latency in the nervous system, and spontaneously reactivate; these features mimic some of the key features of HSV-2 infection in women. RM may provide an animal model to develop strategies to prevent HSV-2 acquisition and reactivation.

Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25–0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34–1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66–2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

Use of injectable hormonal contraception and HSV-2 acquisition in a cohort of female sex workers in Vancouver, Canada

ObjectivesIncreased risk of herpes simplex virus 2 (HSV-2) has been proposed as a possible indirect pathway through which hormonal contraceptives (specifically depot medroxyprogesterone acetate (DMPA)) may increase the risk of...

S06.2 Herpes simplex virus vaccine development: pipelines and possibilities

Genital herpes simplex virus (HSV) infection causes recurrent genital ulcers, neonatal herpes, and increases the risk of HIV acquisition. HSV-2, the most common cause of genital herpes, is highly prevalent worldwide, with an estimated 417 million people infected between the ages of 15–49. The urgent need for a prophylactic vaccine against genital HSV has been long recognized. Multiple glycoprotein subunit vaccines candidates have been tested but none have successfully prevented HSV-2 genital ulcer disease in phase III trials. Despite these findings, there is strong interest in pursuing novel vaccine platforms to induce immune responses to protect against HSV acquisition. Therapeutic vaccines to reduce genital symptoms and viral shedding in persons already infected with HSV-2 are also being tested in early phase clinical trials. The global STI vaccine roadmap provided a framework for research priorities to move the HSV vaccine field forward. This presentation will review 1) lessons from prior clinical trials of HSV vaccines, 2) new insights into immunology of HSV infection, 3) current status of HSV vaccine pipeline, with an emphasis on candidates currently in clinical trials and 4) discussion of clinical trial design issues unique to HSV.

S01.3 Making Anal Sex Safe: Current Status of Products For Rectal Use

There are no products available that make anal sex completely safe from the point of view of HIV acquisition, and the likelihood of this happening in the future is slim....

Preventing Neonatal Transmission of Herpes Simplex Virus

Herpes simplex virus (HSV) infections are highly prevalent and may have devastating consequences if transmitted to newborns. The highest risk of transmission is when the mother has primary HSV infection (rather than recurrence of chronic infection) late in pregnancy. Clinicians should obtain a careful history, performing serologic testing and counseling as appropriate. Delayed diagnosis of neonatal HSV is associated with high mortality. Even with adequate treatment, permanent sequelae, such as cerebral palsy and developmental delay, may occur. Clinicians should develop prudent strategies to avoid primary HSV acquisition during pregnancy, and provide prophylaxis or treatment when indicated.

Safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring

Systemic aciclovir and its prodrug valaciclovir are effective in treating and reducing recurrences of genital herpes simplex virus (HSV) and reducing transmission. Local aciclovir delivery, if it can achieve and maintain comparable intracellular genital tract levels, may be equally effective in the treatment and suppression of genital HSV. Intravaginal ring (IVR) delivery of aciclovir may provide pre-exposure prophylaxis against HSV acquisition. Tolerability and pharmacokinetics were evaluated in six HIV-negative women with recurrent genital HSV who switched their daily oral valaciclovir suppression to an aciclovir IVR for 7 days (n = 3) or 14 days (n = 3). Blood and cervicovaginal lavage (CVL) were collected after oral and IVR dosing to measure aciclovir concentrations and genital swabs were obtained to quantify HSV shedding by PCR. The rings were well tolerated. Median plasma aciclovir concentrations were 110.2 ng/mL (IQR, 85.9-233.5) 12-18 h after oral valaciclovir. Little or no drug was detected in plasma following IVR dosing. Median (IQR) CVL aciclovir levels were 127.3 ng/mL (21-660.8) 2 h after oral valaciclovir, 154.4 ng/mL (60.7-327.5) 12-18 h after oral valaciclovir and 438 ng/mL (178.5-618.5) after 7 days and 393 ng/mL (31.6-1615) after 14 days of aciclovir ring use. Median CVL aciclovir levels 2 h after oral dosing were similar to levels observed 7 (P = 0.99) and 14 (P = 0.75) days after ring use. HSV DNA was not detected in genital swabs and there was no significant change in inflammatory mediators. This first-in-human study demonstrated that an IVR could safely deliver mucosal levels of aciclovir similar to oral valaciclovir without systemic absorption. More intensive site-specific pharmacokinetic studies are needed to determine whether higher local concentrations are needed to achieve optimal drug distribution within the genital tract.

Incidence, Prevalence, and Epidemiology of Herpes Simplex Virus-2 in HIV-1-Positive and HIV-1-Negative Adolescents

Several studies have assessed risk factors associated with herpes simplex virus-2 (HSV-2) prevalence in adults; however, few have focused on HSV-2 incidence, particularly in adolescents. The objective of this study was to determine HSV-2 prevalence and incidence and associated risk factors in a HIV-1-positive and at risk HIV-1-negative adolescent population. Sera were tested for HSV-2 antibodies in 518 adolescents in the Reaching for Excellence in Adolescent Care and Health cohort at baseline and again at the final follow-up visit. Prevalence at baseline and incidence (per person years) of HSV-2 infection were calculated. Furthermore, among HIV-1-positive individuals, a subgroup analysis was performed to assess risk factors for HSV-2 infection. Conditional logistic regression was used to estimate odds ratios and P values for associations between CD4+ T-cell (CD4+) count, HIV-1 viral load (VL), and HSV-2 acquisition, adjusting for antiretroviral therapy use, other sexually transmitted infections, gender, race, and number of sexual partners. At baseline, 179 (35%) subjects were HSV-2 positive, with an additional 47 (16%) new cases being identified during a median follow-up time of 1.95 years and an incidence rate of 7.35 cases per 100 person years. Several risk factors were associated with HSV-2 prevalence (being female, non-Hispanic, uncertainty of sexual preference, and HIV-1 positive) and incidence (using drugs, alcohol, and number of new sexual partners). Among HIV-1 positives, an increase in CD4+ count by 50 cell/mm(3) (odds ratio, 1.17; 95% CI, 1.04-1.31, P = 0.008) was associated with HSV-2 acquisition. The high prevalence and incidence of HSV-2 infection among adolescents, compared with the general population at this age group suggests a critical need for screening and preventive programs among this targeted group.

Tenofovir-based pre-exposure prophylaxis for HIV prevention

Topical tenofovir gel and oral tenofovir and emtricitabine-tenofovir [FTC/tenofovir disoproxyl fumarate (TDF)] have been demonstrated to have efficacy in preventing HIV-1 in some populations. Preexposure prophylaxis (PrEP) trials and future directions are summarized. Pericoital use of 1% tenofovir gel in the CAPRISA 004 study reduced HIV-1 acquisition by 39% and herpes simplex virus-2 acquisition by 51%. Daily oral FTC/TDF demonstrated 44% reduction in HIV-1 acquisition among MSM in the iPrEx study (Pre-Exposure Prophylaxis Initiative). Both studies showed higher efficacy among those with higher adherence. Efficacy of daily oral TDF and FTC/TDF was 66 and 73%, respectively, among HIV-1-uninfected partners in an HIV-1 serodiscordant partnership in the Partners PrEP Study. Efficacy of daily oral FTC/TDF was 66% in young heterosexuals in Botswana in the TDF2 trial. The FEM-PrEP and VOICE (Vaginal and Oral Interventions to Control the Epidemic) studies in African women found no efficacy with oral FTC/TDF and TDF, respectively. Safety and tolerability were excellent and limited resistance was observed in seroconverters. Topical tenofovir gel showed efficacy in African women and daily oral TDF and FTC/TDF were efficacious in MSM, and African HIV-1 serodiscordant couples and young heterosexuals. The reasons for lack of efficacy of oral FTC/TDF and TDF in two studies in African women are being investigated. Longer-acting formulations, invtravaginal rings, and new candidate antiretrovirals are being evaluated for pre-exposure prophylaxis (PrEP).

Herpes Simplex Virus Type 2 Infection in Young Adult Women: Risk Factors for Infection and Frequency of Viral Shedding

Population-based studies suggest that acquisition of herpes simplex virus 2 (HSV 2) is most common between ages 20 and 29, especially in minority women. We examined HSV 2 infection and viral shedding in a cohort of young women. Women, age 18 to 24 (median 21), who were part of an observational cohort enrolled between ages 14 to 17, had blood obtained for HSV 2 antibody. Intensive diary collections on sexual behavior and genital symptoms and weekly vaginal swabs were obtained at regular intervals. HSV 2 antibodies were detected in 43 of 127 participants (33.9%), only 4 of whom were previously known to be positive. Factors associated with a positive test included older age, years of sexual activity, and number of lifetime partners. Testing for HSV 2 DNA by polymerase chain reaction on weekly vaginal swabs from a 13-week sampling period for each HSV 2 antibody positive participant showed 32 of 43 (74.4%) were positive at least once. The positive predictive value of pain for viral shedding was poor. HSV 2 infection is very common among young adult women, but symptomatic genital herpes is not. Shedding of HSV 2 DNA can be detected in most antibody positive persons. Early intervention strategies will be needed to control HSV 2 infection.

A Pooled Analysis of the Effect of Condoms in Preventing HSV-2 Acquisition

The degree of effectiveness of condom use in preventing the transmission of herpes simplex virus 2 (HSV-2) is uncertain. To address this issue, we performed a large pooled analysis. We identified prospective studies with individual-level condom use data and laboratory-defined HSV-2 acquisition. Six studies were identified through a review of publications through 2007: 3 candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational sexually transmitted infection (STI) incidence study, and a behavioral STI intervention study. Study investigators provided us individual-level data to perform a pooled analysis. Effect of condom use was modeled using a continuous percentage of sex acts during which a condom was used and, alternatively, using absolute numbers of unprotected sex acts. A total of 5384 HSV-2-negative people at baseline contributed 2 040 894 follow-up days; 415 persons acquired laboratory-documented HSV-2 during follow-up. Consistent condom users (used 100% of the time) had a 30% lower risk of HSV-2 acquisition compared with those who never used condoms (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.40-0.94) (P = .01). Risk for HSV-2 acquisition increased steadily and significantly with each unprotected sex act (HR, 1.16; 95% CI, 1.08-1.25) (P < .001). Condom effectiveness did not vary by gender. To our knowledge, this is the largest analysis using prospective data to assess the effect of condom use in preventing HSV-2 acquisition. Although the magnitude of protection was not as large as has been observed with other STIs, we found that condoms offer moderate protection against HSV-2 acquisition in men and women.

Understanding Herpes Simplex Virus: Transmission, Diagnosis, and Considerations in Pregnancy Management

Genital herpes simplex virus (HSV) infections are frequently asymptomatic or undiagnosed, but more than half the US population is seropositive for HSV, and about one-fifth are positive for HSV-2. These two factors contribute to the risk for sexual transmission and therefore to the risk of late-pregnancy acquisition of HSV. Most neonatal herpes infections are the result of undiagnosed, new-onset HSV infection in the mother. This article reviews the epidemiology of HSV, risks of transmission, and testing and management of HSV during pregnancy. Options for evaluation and management are presented.

HIV-1/HSV-2 co-infected adults in early HIV-1 infection have elevated CD4+ T cell counts.

IntroductionHIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2). We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes.MethodsWe assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naïve adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status.ResultsOf 186 recently HIV-1 infected persons, 101 (54 %) were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04) than those with HIV-1 infection alone (Figure 1), after adjustment for HIV-1 RNA levels (−57 cells per 1 log10 higher HIV-1 RNA, p<0.0001). We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquistion after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status.DiscussionWe observed no effect of HSV-2 status on viral load. However, we did observe that treatment naïve, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.

Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes

Neonatal herpes simplex virus (HSV) is a rare but devastating disease. We have conducted pooled analyses of data from 3 cohorts to evaluate the effects of maternal HSV serostatus and HSV type on risk of neonatal HSV acquisition and severity. Data from cohorts in Seattle, WA, and Stanford, CA, USA, and Stockholm, Sweden were pooled using Mantel-Haenszel methods. Seventy-eight infants with documented neonatal HSV and known maternal HSV serostatus were included. The risk of neonatal HSV-2 infection was similar in infants born to HSV seronegative women compared with HSV-1 seropositive women (pooled OR: 1.6; 95% CI: 0.6-4.0). The odds of neonatal HSV infection was increased in the presence of exposure to maternal HSV-1 versus HSV-2 (adjusted pooled OR: 19.2; 95% CI: 5.8-63.6). An elevated odds of disseminated HSV in infants born to women with newly acquired genital herpes was observed in Stockholm (OR=13.5; 95% CI: 1.4-630), but not in Seattle or Stanford. Our results suggest that maternal HSV-1 antibody offers little, if any, protection against neonatal HSV-2 infection. During reactivation, HSV-1 appears more readily transmissible to the neonate than HSV-2, a concerning finding given the rising frequency of genital HSV-1 infection.

Risk Factors for Herpes Simplex Virus Transmission to Pregnant Women: A Couples Study

An estimated 60% to 80% of neonatal herpes simplex virus (HSV) infections are a result of the mother acquiring HSV-1 or HSV-2 close to the time of delivery. Although it is relatively uncommon for HSV to be acquired at the end of pregnancy, transmission takes place efficiently. This suggests that preventing maternal acquisition of HSV during pregnancy may effectively lower the risk of neonatal infection. This couples study was done to identify risk factors for acquiring HSV in at-risk pregnant women who were participating in a prospective study of HSV in pregnancy. They invited their partners to undergo serologic testing for type-specific HSV. A total of 3192 couples took part in the study. Serum samples were taken at the initial prenatal visit and again at the time of labor, and swabs were taken at labor from the external genitalia and cervix. Antibodies to HSV-1 and HSV-2 were sought by the Western blot technique. Just over one fifth of women in the study were at risk of acquiring HSV. Of 582 who were seronegative for HSV-1 and whose partners were seropositive, 14 (3.5% when adjusted for gestational length) did acquire HSV-1. Having a partner with a history of oral herpes correlated with acquisition of HSV-1 (odds ratio [OR] 8.1; 95% confidence interval [CI], 1.8-36) and accounted for three fourths of incident infections. Of 125 women at risk for acquiring HSV-2, 17 (20% when adjusted for gestational length) became infected. Partnership for 12 months or less correlated with acquiring HSV-2 (OR, 7.8; 95% CI, 2.3-25.7) and accounted for 63% of incident infections. The presence of HSV-1 antibodies did not influence the rate of acquiring HSV-2 to any substantial degree. The rate of subclinical infection in 31 women who acquired HSV from their partners during pregnancy was 68%. The rate did not depend on whether the women acquired HSV-1 or HSV-2. There was a single case of neonatal herpes. No set of clinical features was found that identified a majority of susceptible women having serologically discordant partners. These findings imply that serologic screening may be necessary to identify women who are at risk of acquiring HSV while pregnant. Acquisition rates, especially those for HSV-2, are high for serologically discordant couples. Further studies are needed to determine the cost of serologically screening pregnant women and to what degree this practice will prevent maternal and neonatal HSV infections.

Risk factors for herpes simplex virus transmission to pregnant women: A couples study

This study was undertaken to determine risk factors for herpes simplex virus (HSV) acquisition among at risk pregnant women. Women in a prospective study of HSV acquisition in pregnancy invited their sexual partners for HSV type-specific serologic testing. Risk factors for HSV susceptibility, exposure, and acquisition were examined. A total of 3192 couples enrolled; 22% included women at risk for HSV-1 or HSV-2. Among 582 HSV-1 seronegative women with HSV-1 seropositive partners, 14 (3.5% adjusted for gestation length) acquired HSV-1. Having a partner with a history of oral herpes was associated with HSV-1 acquisition (odds ratio [OR] 8.1, 95% CI: 1.8-36.0) and accounted for 75% of incident infections. Among 125 HSV-2 seronegative women with HSV-2 seropositive partners, 17 (20% adjusted for gestation length) acquired HSV-2. Duration of partnership of 1 year or less was associated with HSV-2 acquisition (OR 7.8, 95% CI: 2.3-25.7) and accounted for 63% of incident infections. No combination of clinical characteristics could identify the majority of susceptible women with serologically discordant partners. HSV acquisition rates in pregnancy are high in discordant couples, especially for HSV-2. Interventions that address risk factors for HSV acquisition should be studied in pregnancy. Clinical profiles cannot replace serologic screening to identify susceptible women with serologically discordant partners.

New management of the pregnant patient to reduce the risk of transmitting herpes to the newborn

Growing understanding of the mechanisms and epidemiology of neonatal herpes simplex virus acquisition allows for the development of a new management of the pregnant patient, one that will reduce the risk of transmitting herpes to the newborn. Maternal herpes simplex virus infection, especially acquired during pregnancy, can result in transmission to the newborn. Infection of the CNS of the newborn results in death or significant neurodevelopmental impairment in most of these infected babies. Herpes simplex virus infection acquired prior to or during pregnancy has a physical and psychologic impact on the health of the mother. Newer, more sensitive and specific serology testing for herpes simplex virus in combination with antiviral pharmacotherapy is now recognized as an important option for reducing the risk of herpes simplex virus transmission from mother to newborn. This review discusses new information concerning the prevention, diagnosis and treatment options for the management of herpes simplex virus infection during pregnancy with a focus on the evolving role of prevention.