Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model.

Herpes simplex virus type 2 (HSV-2) infection affects 24 million births annually and is associated with adverse pregnancy outcomes, including neonatal herpes; however, the mechanisms underlying in utero transmission of HSV-2 are largely unknown. We examined the effects of primary HSV-2 infection during early pregnancy on gestational outcomes in a novel, clinically relevant mouse model. Pregnant C57BL/6 mice were infected intravaginally with 102-105 pfu/mL HSV-2 on gestation day (gd) 4.5. Controls were infected, nonpregnant, diestrus-staged mice and pregnant, uninfected mice. Compared to nonpregnant mice, pregnant mice were 100-fold more susceptible to HSV-2 infection. Three days post-inoculation (gd7.5), viral DNA was present in implantation sites, but pregnancy outcomes were largely unaffected by infection. Eight days post-inoculation (gd12.5), HSV-2 DNA persisted in placental tissues, resulting in inflammation and hemorrhage. Fetal and placental weights were reduced and fetal loss was observed with high viral doses. HSV-2 DNA and increased expression of pro-inflammatory mediators were detected in fetal tissues at gd12.5, signifying viral transmission and fetal infection, even with low viral doses. This mouse model shows a dose-dependent effect of primary HSV-2 infection on pregnancy outcomes and suggests that fetal loss may occur due to placental inflammation, thus providing valuable insight into in utero transmission of HSV-2.

Sexually Transmitted Infections: Part I: Genital Bumps and Genital Ulcers.

Sexually transmitted infections (STIs) affect young people in a disproportionate way, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Pediatricians should be familiar with the social, behavioral, and biological factors that predispose adolescents to STIs. Preventive visits for teens and pre-teens should incorporate education and counseling about sexuality, safe sexual behavior, and STIs. Pediatricians should be able to identify, diagnose, and manage STIs presenting as genital "bumps" and genital "ulcers." Pediatricians should also offer human immunodeficiency virus testing and expedited partner treatment to all adolescents who are diagnosed as having an STI.

Management of Genital Herpes in Pregnancy: ACOG Practice Bulletin Summary, Number 220.

Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to the developing fetus and newborn. Genital herpes is common in the United States. Among 14- to 49-year-old females, the prevalence of HSV-2 infection is 15.9%. However, the prevalence of genital herpes infection is higher than that because genital herpes is also caused by HSV-1 (1). Because many women of childbearing age are infected or will be infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a major health concern. This document has been revised to include that for women with a primary or nonprimary first-episode genital HSV infection during the third trimester of pregnancy, cesarean delivery may be offered due to the possibility of prolonged viral shedding.

Management of Genital Herpes in Pregnancy: ACOG Practice Bulletinacog Practice Bulletin, Number 220.

Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to the developing fetus and newborn. Genital herpes is common in the United States. Among 14- to 49-year-old females, the prevalence of HSV-2 infection is 15.9%. However, the prevalence of genital herpes infection is higher than that because genital herpes is also caused by HSV-1 (). Because many women of childbearing age are infected or will be infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a major health concern. This document has been revised to include that for women with a primary or nonprimary first-episode genital HSV infection during the third trimester of pregnancy, cesarean delivery may be offered due to the possibility of prolonged viral shedding.

Genital herpes and pregnancy: Evaluating practices and knowledge of French health care providers.

BACKGROUND: Genital herpes during pregnancy is a frequent occurrence, whereas infection of newborns is rare but likely severe. In the absence of specific national guidelines from the CNGOF (French National College of Gynaecologists and Obstetricians) in France until December 2017, we supposed that knowledge of health care providers on the topic was not up to date. OBJECTIVE: To assess health care provider knowledge of genital herpes and management practices during pregnancy, before the publication of national recommendations edited by the CNGOF. STUDY DESIGN: A questionnaire on genital herpes during pregnancy was published on the CNGOF website and sent by e-mail to members of the French College of Fetal Ultrasound (CFEF). Questions focused on prevention and screening practices, epidemiological knowledge, and management of herpes infection during pregnancy and after birth. RESULTS: Between April and June 2017, 354 health care providers completed the survey (263/354 (75 %) Obstetrician-Gynaecologists, 85/354 (24 %) Midwives and 6/354 (2%) General Practitioners). Overall, obstetricians were better informed about epidemiology of Herpes Simplex Virus (HSV), midwives were more familiar with neonatal risks in case of maternal primary infection but overestimated risks in case of maternal recurrence. 21 % of health care providers never prescribed antiviral prophylaxis in the third trimester if genital herpes occurred during pregnancy. Finally, most practitioners were unaware of newborn management in case of maternal genital herpes at delivery. CONCLUSION: Management of genital herpes in pregnancy appears to be heterogeneous due to varying degrees of knowledge among French health care providers. This highlights the urgent need for national guidelines, that were published 5 months after this study. They should be broadly disseminated and adapted to the shortcomings of health professionals. It would be interesting to repeat this study later to evaluate the impact of national guidelines.

Prevention and treatment of neonatal herpes simplex virus infection.

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a well-known cause of infections including genital herpes and herpes labialis in the adolescent and adult population. Transmission of HSV infection to an infant during the first 4-6 weeks of life can lead to devastating disease with the potential for poor outcomes. Early diagnosis is imperative when evaluating neonatal HSV infection in order to prevent further disease progression, neurological complications, and even death. In the past 4 decades, significant advancements have been made in the diagnosis, treatment, and prevention of neonatal HSV infection, but there remains room for improvement as efforts continue to reduce the burden of disease caused by this infection.

Preventing HIV and HSV-2 through knowledge and attitudes: A replication study of a multi-component community-based intervention in Zimbabwe.

INTRODUCTION: Approximately two-thirds of HIV-infected individuals reside in sub-Saharan Africa. The region accounts for 68% of the new HIV infections occurring worldwide with almost one-half of these infections being among young adults aged 12-24 years. Cowan and colleagues conducted a community-based, multi-component HIV intervention aimed at youth in rural Zimbabwe. Despite some changes in knowledge and attitudes, the community-based intervention did not affect the prevalence of HIV or HSV-2. We selected this frequently cited study for replication since it incorporates individual-, community-, and structural- level intervention components that are often considered in global HIV/AIDS prevention programs. Additionally, the intervention could be easily scaled-up, which is especially important in the context of limited resources. Although this study indicated no intervention effects in reducing HIV, the authors acknowledged some key methodological challenges. Our replication analysis provided important insights regarding the impact of these challenges to the interpretation of the results of this study. METHODS: Our replication study focused on replicating Cowan's findings and assessing the robustness of Cowan's results to alternative analytical models based on their study design. We determined how out-migration occurring during Cowan's study may have affected the population characteristics, the intervention exposure level, and the study findings. While the original intervention targeted knowledge and attitudes as a mechanism to decrease HIV/HSV-2, the Cowan study evaluated the intervention effects on knowledge, attitudes, and prevalence of HIV or HSV-2 separately. To better identify the pathway describing the interrelationship among the intervention and knowledge, attitudes, and prevalence of HIV or HSV-2, we assessed whether increases in knowledge or attitudes were associated with decreased HIV or HSV-2 prevalence. RESULTS: We replicated the original findings with minor discrepancies during the pure replication. Our additional analyses revealed that the study population characteristics changed over time in ways that may have affected outcomes. These changes also affected the levels of intervention exposure, with 48.7% males and 75.5% females of the intervention group receiving low-level exposure. Both genders with higher level intervention exposure experienced higher increments in multiple knowledge, attitude, and sexual risk behavior outcomes. Unfortunately, these did not translate to a significant reduction in HIV or HSV-2 regardless of the level and combination of knowledge and attitude domains. However, males receiving high-level intervention exposure compared to control indicated significantly lower odds of having HIV or HSV-2 under a Bayesian modeling paradigm. CONCLUSIONS: Our findings suggest a more robust conclusion on the study intervention effects. Further study based on a design that more consistently maximizes the exposure level of the intervention is necessary and should ideally be an evaluated goal in similar studies. Evaluation of the intervention impact for key subgroups of the target population is important and would better advise the use and scale-up of the evaluated interventions in various contexts. Our observation of a consistent lack of relationship between knowledge/attitudes and HIV/HSV-2 suggests a need to explore and include relevant additional and or complementary interventions, e.g., promoting effective skills in reducing risky sexual behaviors and addressing cultural and structural bottlenecks that may reduce HIV/HSV-2 risk among youth.

Herpes Simplex Virus Type 2 Seroprevalence in Pregnant Women in Urmia, Northwest of Iran, during 2014-2015

Background: Herpes simplex virus type 2 (HSV-2) seroprevalence has been shown to be a potential sign of infection in pregnant women, and it could be applied to check HSV-2 transmission. This study evaluated the anti-HSV-2 IgG prevalence in pregnant women who were referred to health centers in Urmia, Northwest of Iran, during 2014-2015. Methods: Serum samples were collected from 86 pregnant women and tested for Anti-HSV-2-specific IgG using a commercial enzyme-linked immunosorbent assays kit. Results: Five (5.8%) pregnant women showed the presence of Anti-HSV-2-specific IgG antibodies. Previous abortion was reported in 16 (19.7%) and 2 subjects in the seronegative and seropositive groups, respectively. Conclusion: Data from the present study indicate a lower number of HSV-2 seropositives among the pregnant women in Urmia. This reduction would be a result of low number of studied subjects used in the present study; hence, assessing a large sample is recommended.

[Diagnostic and therapeutic recommendations for sexually transmitted diseases: Genital herpes]. / Recommandations diagnostiques et thérapeutiques pour les maladies sexuellement transmissibles : herpès génital au cours de la grossesse.

TREATMENT OF THE INITIAL INFECTION OR FIRST CLINICAL EPISODE OF GENITAL HERPES: An initial infection or first clinical episode of genital herpes is treated with oral aciclovir 200mg×5/d for 5 to 10 days depending on clinical status. The recommended dosage for valaciclovir is 1g×2/d and treatment duration is identical to that for aciclovir. TREATMENT OF HERPES RECURRING DURING PREGNANCY: There are no studies of the efficacy of antiviral therapy on the symptoms of genital recurring during pregnancy. However, initial anti-viral treatment using aciclovir or valaciclovir may be given where warranted by symptoms (i.e. duration and severity of symptoms). Valaciclovir may be used instead (equivalent efficacy but better safety data for aciclovir). Valaciclovir may be given at a dosage of 1×500mg b.i.d. p.o. for 5 days. PROPHYLACTIC ANTI-VIRAL TREATMENT DURING PREGNANCY: In female patients presenting an initial infection or infection recurring during pregnancy, although there is no demonstrated benefit for prophylactic treatment in reducing the risk of neonatal herpes, anti-viral prophylaxis is recommended after 36 WA (weeks' amenorrhoea) to limit the need for Caesarean section due to herpetic lesions. The recommended antivirals are aciclovir at a dosage of 400mg t.i.d p.o. or valaciclovir at a dosage of 500mg b.i.d. p.o. until delivery.

Should Caesarian Section Be Offered to Women With Recurrent Genital Herpes Simplex Lesions After >4 Hours of Ruptured Membranes?

BACKGROUND: Neonatal herpes simplex virus (HSV) infection and its implications have been well defined. Several methods are recommended to mitigate the risk of maternal transmission of HSV to the neonate, including CS, suppressive antiviral therapy for the mother, and prophylaxis for the infant. The utility of CS in women who present with a duration of rupture of membranes greater than 4 hours remains a question. CASE: We present a case of a woman who presented following 10 hours of rupture of membranes with HSV genital lesions, suspected to be the result of untreated recurrent infection. A CS was done. CONCLUSION: Extensive studies for the presence of HSV by PCR of the placenta and infant failed to detect the virus.

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels. Methods: The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence. Results: A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001). Conclusions: There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

Neonatal herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.

Prevention and management of genital herpes simplex infection during pregnancy and delivery: Guidelines from the French College of Gynaecologists and Obstetricians (CNGOF).

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

Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health Problem of Increasing Concern?

BACKGROUND: This article provides an update on the incidence of neonatal herpes, guideline adherence by health care professionals (HCP) and trends in genital herpes simplex virus (HSV) infection during pregnancy in the Netherlands. METHODS: Questionnaires were sent to all hospitals inquiring about numbers and characteristics of neonatal and maternal HSV infections, and guideline adherence between 2012 and 2015. Longitudinal trends were investigated from 1999 onward using survey data and Perinatal Registry of the Netherlands data (Perined). Trends were smoothed with Poisson regression splines. Risk indicators for neonatal and maternal HSV infections were examined with Poisson regression analyses. RESULTS: Neonatal herpes incidence was 4.8/100,000 live births based on survey data (2012-2015) and 3.4/100,000 based on Perined (2012-2014). Mortality rate was 23% (7/30). Neonatal herpes incidence increased slightly over time as did the prevalence of genital HSV infection among pregnant women. Non-Western ethnicity (Rate Ratio: 1.9; 95% confidence interval: 1.5-2.5) and age <20 years (Rate Ratio: 2.3; 95% confidence interval: 1.2-4.7) were associated with genital herpes during pregnancy. In Perined, none of the neonatal herpes cases had a mother diagnosed with an active genital herpes infection during pregnancy. Preventive measures to reduce vertical herpes transmission (such as cesarean section) were less commonly reported by HCP in 2012-2015 compared with 2006-2011. CONCLUSIONS: Neonatal herpes incidence in the Netherlands slowly increased over the last 15 years. An increased genital HSV prevalence during pregnancy or, to lower extent, the decreased guideline adherence by HCP may be responsible. A rise in asymptomatic maternal HSV shedding is also plausible, emphasizing the challenges in preventing neonatal herpes.

HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study.

OBJECTIVES: To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy. METHODS: An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses. RESULTS: Assuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs. CONCLUSIONS: It is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition.

Associations between friendship characteristics and HIV and HSV-2 status amongst young South African women in HPTN-068.

INTRODUCTION: Prevalence of HIV among young women in South Africa remains extremely high. Adolescent peer groups have been found to be an important influence on a range of health behaviours. The characteristics of young women's friendships might influence their sexual health and HIV risk via connections to sexual partners, norms around sexual initiation and condom use, or provision of social support. We investigated associations between young women's friendships and their Herpes Simplex Virus Type 2 (HSV-2) and HIV infection status in rural South Africa. METHODS: Our study is a cross-sectional, egocentric network analysis. In 2011 to 2012, we tested 13- to 20-year-old young women for HIV and HSV-2, and collected descriptions of five friendships for each. We generated summary measures describing friend socio-demographic characteristics and the number of friends perceived to have had sex. We used logistic regression to analyse associations between friend characteristics and participant HIV and HSV-2 infection, excluding likely perinatal HIV infections. RESULTS: There were 2326 participants included in the study sample, among whom HIV and HSV-2 prevalence were 3.3% and 4.6% respectively. Adjusted for participant and friend socio-demographic characteristics, each additional friend at least one year older than the participant was associated with raised odds of HIV (odds ratio (OR) = 1.37, 95% CI 1.03 to 1.82) and HSV-2 (adjusted OR=1.41, 95% CI 1.18 to 1.69). Each additional friend perceived to have ever had sex also raised the odds of HIV (OR = 1.29, 95% CI 1.03 to 1.63) and HSV-2 (OR=1.18, 95% CI 1.03 to 1.35). DISCUSSION: We found good evidence that a greater number of older friends and friends perceived to have had sex were associated with increased risk for HSV-2 and HIV infection among young women. CONCLUSIONS: The characteristics of young women's friendships could contribute to their risk of HIV infection. The extent to which policies or programmes influence age-mixing and young women's normative environments should be considered.

[Genital herpes and pregnancy: Epidemiology, clinical manifestations, prevention and screening. Guidelines for clinical practice from the French College of Gynecologists and Obstetrician (CNGOF)]. / Herpès génital et grossesse : épidémiologie, manifestations de la maladie, prévention et dépistage. Recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français (CNGOF).

OBJECTIVES: To analyze the consequences of genital herpes infections in pregnant women. METHODS: The PubMed database and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: The symptomatology of herpes genital rash is often atypical (NP2) and not different during pregnancy (Professional consensus). It is most often due to HSV2 (NP2). Seventy percent of pregnant patients have a history of infection with Herpes simplex virus, without reference to genital or labial localization, and this is in most cases type 1 (NP2). The prevalence of clinical herpes lesions at birth in the event of recurrence is about 16% compared with 36% in the case of initial infection (NP4). In HSV+ patients, asymptomatic herpetic excretion is 4 to 10%. The rate of excretion increases in HIV+ patients (20 to 30%) (NP2). The risk of HSV seroconversion during pregnancy is 1 to 5% (NP2), but can reach 20% in case of sero-discordant couple (NP2). Questioning is not always sufficient to determine the history of herpes infection of a patient and her partner (NP2) and the clinical examination is not always reliable (NP2). Herpetic hepatitis and encephalitis are rare and potentially severe (NP4). These diagnoses should be discussed during pregnancy and antiviral therapy should be started as soon as possible (Professional consensus). There is no established link between herpes infection and miscarriages (NP3). There appears to be an association between untreated herpes infection and premature delivery (NP3) but not in the case of treated infections (NP4). Herpetic fetopathies are exceptional (NP4). There is no argument for recommending specific prenatal diagnosis for herpes infection during pregnancy (Professional consensus). Condom use reduces the risk of initial infection in women who are not pregnant (NP3). There is no evidence to justify routine screening during pregnancy (Professional consensus). CONCLUSION: There is a strong discrepancy between the prevalence of herpetic excretion at the time of delivery and the scarcity of neonatal infections. There is a lack of data on the impact of herpes infections during pregnancy in France. Fetal and maternal consequences are potentially serious but rare.

[Neonatal herpes: Epidemiology, clinical manifestations and management. Guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF)]. / Herpès néonatal : épidémiologie, manifestations cliniques et prise en charge. Recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français (CNGOF).

OBJECTIVES: To describe the epidemiology of neonatal herpes and its risk factors, clinical and paraclinic manifestations, propose guidelines for a newborn at risk of neonatal herpes, describe treatment modalities, describe post-natal transmission and its prevention. METHODS: Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines. RESULTS: Neonatal herpes is rare (about 20 cases per year in France) and mainly due to HSV 1 (level of evidence LE3). The main risk factors for mother-to-child transmission are maternal primary episode of genital herpes close to delivery and serotype HSV 1 (LE3). There are three clinical forms of neonatal herpes : SEM infection for skin, eyes and mucosa, central nervous system (CNS) associated infection, and the disseminated infection. Neurological mortality and morbidity depend on the clinical form and the HSV serotype (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE3). Fever and vesicular rash may be absent at the time of diagnosis (LE3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (Professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous aciclovir (Grade A) prior to the results of HSV PCR (Professional consensus). In case of maternal genital herpes at delivery, the management of an asymptomatic newborn depends on the evaluation of the risk of transmission. In case of maternal reactivation (low risk of transmission), HSV PCR samples are taken at 24hours of life and the newborn must be follow closely until results. In the case of maternal primary episode or non-primary infection first episode (high risk of transmission), the samples are taken at 24hours of life and intravenous treatment with aciclovir is started (Professional consensus). The treatment of neonatal herpes is based on intravenous aciclovir (60mg/kg/day divided into 3 injections) (Grade C). The duration of the treatment depends on the clinical form (14 days for the SEM infection, 21 days for the other forms) (Professional consensus). A relay with aciclovir per os (300mg/m2/day) for 6 months is recommended to improve the neurological outcome and reduce the risk of reactivation (grade B). Post-natal transmission is mainly due to HSV 1. The rules for the prevention of post-natal transmission must be known by parents and family, but also by nursing staff (Professional consensus). Breastfeeding is not contraindicated in cases of maternal herpes, except if there is herpetic lesion on the nipple (Professional consensus). Parents of newborns at risk for neonatal herpes should receive information on the clinical signs to be monitored at home after hospital discharge (Professional consensus). CONCLUSIONS: Neonatal herpes is a rare disease with a high morbidity and mortality. The management of a newborn at risk requires good coordination between the obstetric and pediatric teams and parent's information.

[Management of pregnant women with recurrent herpes. Guidelines for clinical practice from the French College of Gynecologists, Obstetricians (CNGOF)]. / Suspicion de lésion d'herpès génital chez une femme enceinte ayant un antécédent d'herpès génital connu. Recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français (CNGOF).

OBJECTIVE: To provide guidelines for the management of woman with genital herpes during pregnancy or labor and with known history of genital herpes. METHODS: MedLine and Cochrane Library databases search and review of the main foreign guidelines. RESULTS: Genital herpes ulceration during pregnancy in a woman with history of genital herpes correspond to a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir or valacyclovir can be administered but provide low efficiency on duration and severity of symptoms (Grade C). Antiviral treatment proposed is acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) for 5 to 10 days (Grade C). Recurrent herpes is associated with a risk of neonatal herpes around 1% (LE3). Antiviral prophylaxis should be offered for women with recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (Grade B). There is no evidence of the benefit of prophylaxis in case or recurrence only before the pregnancy. There is no recommendation for systematic prophylaxis for women with history of recurrent genital herpes and no recurrence during the pregnancy. At the onset of labor, virologic testing is indicated only in case of genital ulceration (Professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and/or in case of prematurity and/or in case of HIV positive woman and vaginal delivery will be all the more considered in case of prolonged rupture of membranes after 37 weeks of gestation in an HIV negative woman (Professional consensus). CONCLUSION: In case of recurrent genital herpes at the onset of labor and intact membranes, cesarean delivery should be considered. In case of recurrent genital herpes and prolonged rupture of membranes at term, the benefit of cesarean delivery is more questionable and vaginal delivery should be considered.