Herpes simplex virus and pregnancy: a review of the management of antenatal and peripartum herpes infections

Genital herpes is one of the most common sexually transmitted infections, affecting 1 in 6 people in the United States. Women are twice as likely to be infected as men and infections in women of reproductive age carry the additional risk of vertical transmission to the neonate at the time of delivery. Neonatal herpes infections can be devastating with up to 50% mortality for disseminated herpes simplex virus (HSV) infections in the newborn. Rates of transmission are affected by the viral type of HSV infection and whether the infection around delivery is primary or recurrent. Current management approaches decrease rates of active lesions at the time of delivery and thereby cesarean deliveries, but have not been shown to decrease the incidence of neonatal herpes infections. More research is needed to better elucidate the risk factors for transmission to the neonate and to improve our current management methodology to further decrease vertical transmission. In this review, we will discuss management of antenatal and peripartum herpes infections, considerations for mode of delivery, and the course of neonatal HSV infections.     

The clinical management of genital herpes

Genital herpes infections may be caused by either the herpes simplex virus type 1 or 2 (HSV-1 or HSV-2). The changing patterns of HSV-1 acquisition in childhood have meant that many individuals will acquire this disease in adult life when at least one third of such late infections will involve the genital area. In many parts of the world, HSV-1 is the principal cause of acquisition of HSV disease. However, the majority of cases of frequent and severe genital disease remain due to HSV-2. The management of genital HSV infections involves a careful assessment of the impact of the disease upon the patient. Such an assessment must take into consideration not only the severity and frequency of the disease, but also the impact of infection upon the patient’s psychosexual well-being as well as any concerns around the management of transmission to partners or neonates. Antiviral therapy, if indicated, can be carefully tailored to maximize its impact on symptoms, complications or concerns.     

Genital herpes complicating pregnancy

Approximately 22% of pregnant women are infected with herpes simplex virus (HSV)-2, and 2% of women will acquire HSV during pregnancy. Remarkably, up to 90% of these women are undiagnosed because they are asymptomatic or have subtle symptoms attributed to other vulvovaginal disorders. Diagnosis of genital herpes relies on laboratory confirmation with culture or polymerase chain reaction assay of genital lesions and type-specific glycoprotein G-based serologic testing. Neonatal herpes is the most severe complication of genital HSV infection and is caused by contact with infected genital secretions at the time of labor. Maternal acquisition of HSV in the third trimester of pregnancy carries the highest risk of neonatal transmission. Despite advances in the diagnosis and treatment of neonatal herpes, little change in the incidence or serious sequelae from this infection has occurred. As such, prevention of the initial neonatal infection is critically important. Obstetricians are in a unique position to prevent vertical HSV transmission by identifying women with genital lesions at the time of labor for cesarean delivery, prescribing antiviral suppressive therapy as appropriate, and avoiding unnecessary invasive intrapartum procedures in women with genital herpes. Enhanced prevention strategies include identification of women at risk for HSV acquisition during pregnancy by testing women and possibly their partners for HSV antibodies and providing counseling to prevent transmission to women in late pregnancy.     

Diagnosis of genital herpes: the role and place of HSV testing in clinical practice

Genital herpes is caused by herpes simplex virus (HSV)-1 and HSV-2. It is an underdiagnosed and undertreated sexually transmitted infection characterised by latency followed by reactivation. The seroprevalence of both types of HSV varies throughout Europe, and HSV-1 is an increasing cause of genital herpes. Transmission is through skin-to-skin contact, and neonatal herpes resulting from transmission during delivery is a particularly serious problem. Diagnosis of genital herpes is not straightforward, and a clinical diagnosis alone is usually insufficient. Correct diagnosis is essential for appropriate management and reduction of transmission. Laboratory diagnosis can be by direct detection of the virus or indirect measurement of antibodies. Direct testing has traditionally been through culture of the virus, but detection of viral nucleic acids by real-time polymerase chain reaction is now considered the gold standard method. Type-specific serological testing based on glycoprotein G also has a role in asymptomatic patients or those with non-specific symptoms and in identifying serodiscordant couples, pregnant women at risk and patients co-infected with HIV and HSV-2. Having made an accurate diagnosis, effective management of genital herpes is by treatment with an oral antiviral agent and patient counselling.     

Seroprevalence, incidence of prenatal infections and reliability of maternal history of varicella zoster virus, cytomegalovirus, herpes simplex virus and parvovirus B19 infection in South-Western Finland

Objective   To study seroprevalence and incidence and fetal transmission of varicella zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2 and parvovirus B19 infections during pregnancy and to evaluate the reliability of maternal past history of VZV, HSV and parvovirus infections.
Design   Prospective study of parturient women.
Setting   South-Western Finland.
Participants   Five hundred and fifty-eight parturient women.
Methods   IgG and IgM antibodies against VZV, CMV, HSV-1 and -2, and parvovirus B19 were measured from maternal serum in the first trimester and at delivery and from cord serum, mother's own information of her past infections was compared with her serological status.
Main outcome measures   Seroprevalence, seroconversions and fetal transmission of VZV, CMV, HSV and parvovirus B19, reliability of maternal history of VZV, HSV and parvovirus B19.
Results   Seroprevalences were 96.2% for VZV, 56.3% for CMV, 54.3% for HSV, 46.8% for HSV-1, 9.3% for HSV-2 and 58.6% for parvovirus B19. Parity was associated with CMV seropositivity, maternal age differed only between HSV-2 seropositive and seronegative women, while area of residence (urban or rural) had no effect. Six seroconversions were observed: two VZV, one CMV and three parvovirus infections. No cases of primary HSV infections occurred. Fetal transmission was observed in two cases of parvovirus infection. No infants with anti-CMV IgM antibodies were born to CMV immunised women. False positive history of chickenpox was given only by 1.5% of the women, history of herpes infections was less reliable, and history of parvovirus infection was unreliable.
Conclusions   Seroprevalence and the risk of viral infections during pregnancy cannot be extrapolated from one pregnant population to another.     

Herpes simplex virus in pregnancy: new concepts in prevention and management

Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases in the United States. It is estimated that 45 million adolescents and adults are infected with genital HSV. Most genital herpes infections in the United States are caused by HSV type 2 (HSV-2), and 25% to 30% of women of reproductive age have HSV-2 antibodies. What is more striking is that genital herpes is frequently under-recognized, and that only 5% to 10% of these women have a history of genital herpes. Because such a small percentage of women are aware of being infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a significant health issue.     

Herpes simplex and HIV infections and preterm PROM

Maternal human immunodeficiency virus (HIV) and genital herpes simplex virus (HSV) infection in pregnancy have potential for vertical transmission that may result in death or morbidity. The risk increases with preterm delivery and prolonged ruptured membranes. When managing preterm premature rupture of membranes, the risk of transmission must be weighed against the risk of prematurity. Before 32 to 34 weeks, expectant management is preferred for patients with well controlled HIV or recurrent active genital HSV infection. For patients with advanced HIV disease or primary genital HSV infection, the risk of vertical transmission is higher and many clinical factors need to be considered.     

Herpes simplex virus

Genital herpes simplex infection remains an infectious disease having widespread consequences for both adult and neonatal populations. Physicians must understand that the psychologic impact of genital HSV infections frequently is more disabling than the physical manifestations. Sensitivity, compassion, and support are necessary from members of the medical community, and psychologic counseling may help patients cope with HSV and all its implications. Similarly, physicians must downplay the hysteria that has been associated with herpesvirus infections, emerging as a result of intense media coverage in the 1970s and 1980s. Minimizing the number of cases of neonatal herpes through identification of infected women during parturition continues to be important. Recent guidelines suggest a rationale for the management of women at risk for genital HSV. Nevertheless, until newer immunologic and serologic techniques become clinically reliable and allow a correct and rapid diagnosis of herpes simplex infection, identification of the infected woman in labor must be made using detailed clinical history, physical examination, and viral culture.     

Acyclovir treatment of primary herpes in pregnancy complicated by second trimester preterm premature rupture of membranes with term delivery: case report

Primary genital herpes simplex virus (HSV) infection in pregnancy is associated with an increased risk of vertical transmission to the fetus, especially with rupture of membranes. Two cases of primary herpes and two cases of recurrent herpes in pregnancy with preterm premature rupture of membranes and expectant management have been reported, all delivering preterm. We report a case of primary maternal genital HSV infection with preterm premature rupture of membranes at 24 weeks' gestation who subsequently went on to deliver at term. This case was managed with intravenous acyclovir. Neonatal serology for HSV I (immunoglobulin M [IgM] and IgG) and HSV II (IgM) were negative. Antibodies for HSV II (IgG) were positive. Subsequent 6-month follow-up titers were negative for all herpes antibodies. On the basis of an extensive search of the English literature from 1966 to 2001, this is the first reported case of primary herpes in pregnancy associated with preterm premature rupture of membranes with a subsequent term delivery.     

Herpes simplex virus infections of the newborn

Herpes simplex virus (HSV) infections are fortunately quite rare in the neonatal population. Nevertheless, due to their life-threatening nature and the tremendous damage that surviving infants can incur, neonatal HSV is actually considered in a differential diagnosis relatively commonly. The availability of safe and effective antiviral therapy for the management of neonatal HSV also can accelerate a clinician's decision to consider HSV as the cause of a neonate's disease presentation, and then to obtain appropriate diagnostic studies and empirically institute antiviral treatment. Decisions on whether to continue antiviral therapy for a full course are predicated on the appropriate interpretation of these diagnostic studies as they subsequently are reported to the treating physician. For HSV-infected neonates, the duration of parenteral acyclovir therapy ranges from 14 to 21 days, depending on the extent of disease. Use of subsequent oral suppressive antiviral therapy is under investigation in randomized controlled trials, and at this time cannot be routinely recommended. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management.     

Adolescent Primary Genital Herpes Simplex Virus Type 1 Infection with Sepsis Secondary to Streptococcus pyogenes Bacteremia

BackgroundAdolescents and young adults are responsible for most new genital herpes virus infections. Historically, primary genital herpes infections were thought to be caused by herpes simplex virus (HSV) type 2, however, recent studies suggest that up to 50% of incident episodes of genital herpes are caused by HSV type 1.CaseIn this case report we present an 18-year-old G1P0010 female who presented with a primary genital HSV type 1 outbreak that resulted in sepsis secondary to Streptococcus pyogenes bacteremia.Summary and ConclusionComplications that might arise from HSV include encephalitis, Bell's palsy, aseptic meningitis, hepatitis, pneumonitis, sacral radiculitis, viremia, and superimposed bacterial infections. HSV infections are rarely associated with these complications; however, physicians should be aware of sepsis secondary to bacteremia as a possible complication of primary genital HSV infections when treating immunocompetent adolescents.     

Herpes simplex virus IgA in pregnancy

From 170 pregnant women, cervico-vaginal secretion, serum and amnion fluid were collected to determine concentrations of herpes simplex virus (HSV) IgA in different risk groups. We found a higher concentration of HSV IgA in cervicovaginal secretions in women with positive cultures, compared with women with negative cultures. Women with a prior history of genital HSV infections also had higher levels of HSV-IgA in cervico-vaginal secretions, compared with those with no HSV history, but the differences were not statistically significant. The concentrations of HSV IgA in cervico-vaginal secretions were not correlated to any other risk group defined in the study. An asymptomatic mother with no previous history of genital HSV infection, but belonging to the risk groups gave birth to an infant who developed neonatal herpes on the 4th day of life. Women at risk for viral shedding during gestation and at the time of delivery cannot be identified solely on the basis of grouping into risk groups and/or on concentration of HSV IgA in cervico-vaginal secretion.     

Issues and management of herpes in pregnancy

Genital herpes simplex virus (HSV) infection during pregnancy poses a significant risk to the developing fetus and newborn. In the United States, the incidence of this sexually transmitted disease has increased since 1970. Since many women of childbearing age are infected or are becoming infected, the risk of maternal transmission of this virus to the fetus or newborn is a major health concern. This review defines the stages of herpetic infection, outlines the spectrum of maternal and neonatal infection, including rates of transmission and risks, and provides management guidelines that have been validated by appropriately conducted outcome-based research.     

Herpesvirus

Herpesvirus (HSV) infection of the genital tract is a sexually transmitted disease that is increasing at an epidemic rate. 2 types of virus, Type 1 (HSV-1) and Type 2 (HSV-2) have been identified, of which HSV-2 is the major cause of genital and neonatal infection. Type 2 herpes infections may be the 2nd most common venereal disease in the US. More than 60% of the adult US population has antibodies to HSV, and socioeconomic factors have been found to influence the incidence of HSV infection. The precise incidence of genital herpes in the US is not known, but in 1979 there were 29.2/100,000 consultations for genital herpes, compared to 3.4/100,000 in 1966. As many as 20 million people have herpes, and there are 5 million new cases/year. Genital herpes occurs more frequently in a sexually active population. Clinical manifestations depend on the immune status of the individual and may be 1st episode primary genital herpes, 1st episode nonprimary genital herpes, or recurrent disease. 85% of primary 1st episode genital herpes are caused by HSV-2, the attack rate for susceptible sexual contacts from individuals with active genital lesions is approximately 75%, and the incubation period averages 6 days. 1st episode primary disease may produce severe localized symptoms as well as systemic symptoms. Complete resolution of lesions takes up to 6 weeks, and symptoms persist for an average of 13.8 days. 1st episode nonprimary genital herpes and recurrent disease have similar clinical courses, with ususally mild local symptoms lasting on average 6.9 days, no systemic symptoms, 1-3 lesions, complete resolution of lesions in 8 days, short duration of viral shedding, and presence of preexisting HSV antibodies. Possible complications of genital herpes infections include urethral and bladder infections and secondary bacterial skin infections, inflammatory radiculomyelitis, transverse myelitis, and aseptic meningitis. Humoral and cell-mediated immune responses are important. The majority of infections are diagnosed clinically. Viral culture is the most reliable laboratory technique. Other venereal diseases commonly coexist with genital herpes. To date there is no effective topical therapy for recurrent genital herpes. Cesarean section has been recommended to avoid infecting infants of infected mothers during delivery. Psychological and emotional problems caused by fears of infecting a sexual partner and increased risk of genital cancer in women are among longterm sequelae of genital herpes.     

Vertical transmission of herpes simplex virus acquired after primary outbreak in second trimester of a dichorionic twin gestation

Background: The incidence of genital herpes simplex virus (HSV) has increased in recent years, particularly among women of reproductive age. This places more neonates at risk for severe morbidity and mortality. Treatment recommendations for primary disease in pregnancy are lacking, particularly for those who acquire. HSV remote from term.Case: A patient at 17 weeks of gestation carrying dichorionic twins developed primary herpes with subsequent vertical transmission of the virus and significant neonatal morbidity.Conclusion: Data regarding risks and benefits of treatments such as acyclovir and immunoprophylaxis are lacking at a time when the incidence of HSV infection is on the rise.     

Gynäkologische Infektionen

Gonorrhea (GO) and genital Chlamydia trachomatis D – K infections (CT) are sexually transmitted and GO has been found more frequently in recent years in risk behavior groups. Infections with CT are frequent in young women, which has led to a (controversially discussed) German screening program. Salpingitis should be diagnosed by laparoscopy because CT and GO are often found only in the fallopian tubes and not in the cervix, which also necessitates a partner treatment. Herpes genitalis causes severe complaints in the first 3 weeks during the primary infection period, especially by herpes simplex virus (HSV) 2. Pregnant women without HSV antibodies and an HSV positive contact person are at risk of acquiring a prepartal infection with the risk of herpes neonatorum. Such women should therefore avoid orogenital contact or sex without condoms and women infected with herpes themselves should receive oral prophylactic treatment with aciclovir 4×200 mg or 3×300 mg during the last 4 weeks of pregnancy to avoid a cesarean section.     

Anogenital HSV in Children: Should Providers Be Concerned for Sexual Abuse?

ObjectiveAnogenital herpes simplex virus (HSV) is most commonly acquired via sexual transmission, although other nonsexual modes of transmission have been proposed. When a child presents with a first-time outbreak of anogenital HSV, providers must consider sexual abuse. There are currently no evidence-based consensus guidelines to inform management of these patients. The purpose of this study was to describe how child abuse pediatricians (CAPs) evaluate children with anogenital HSV infection and determine whether any consistent practice patterns are followed.Participants and SettingThe patients included in this study were children between the ages of 0 and 12 years with a first-time outbreak of anogenital HSV who were medically evaluated by a CAP.MethodsPatient charts were retroactively reviewed for the period of January 1 2004 to May 1 2020.ResultsTwenty-two cases were referred for evaluation by a CAP in the chosen time frame. Fifteen were seen in person. Ten of these patients were interviewed, 15 had an anogenital exam with colposcopy, and 14 were tested for at least one other sexually transmitted infection. A diagnosis of sexual abuse was made for 1 patient.ConclusionThis study demonstrates that although nonsexual transmission of anogenital HSV may be possible, providers must still consider sexual abuse. Children with a first-time outbreak of anogenital HSV should have a comprehensive evaluation for sexual abuse, including interview, physical exam, and testing for sexually transmitted infections. Evidence-based concerns for sexual abuse should be reported to child protective services.     

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.

Sperm viral infection and male infertility: focus on HBV,HCV, HIV,HPV, HSV,HCMV, and AAV

Chronic viral infections can infect sperm and are considered a risk factor in male infertility. Recent studies have shown that the presence of HIV, HBV or HCV in semen impairs sperm parameters, DNA integrity, and in particular reduces forward motility. In contrast, very little is known about semen infection with human papillomaviruses (HPV), herpesviruses (HSV), cytomegalovirus (HCMV), and adeno-associated virus (AAV). At present, EU directives for the viral screening of couples undergoing assisted reproduction techniques require only the evaluation of HIV, HBV, and HCV. However, growing evidence suggests that HPV, HSV, and HCMV might play a major role in male infertility and it has been demonstrated that HPV semen infection has a negative influence on sperm parameters, fertilization, and the abortion rate. Besides the risk of horizontal or vertical transmission, the negative impact of any viral sperm infection on male reproductive function seems to be dramatic. In addition, treatment with antiviral and antiretroviral therapies may further affect sperm parameters. In this review we attempted to focus on the interactions between defined sperm viral infections and their association with male fertility disorders. All viruses considered in this article have a potentially negative effect on male reproductive function and dangerous infections can be transmitted to partners and newborns. In light of this evidence, we suggest performing targeted sperm washing procedures for each sperm infection and to strongly consider screening male patients seeking fertility for HPV, HSV, and HCMV, both to avoid viral transmission and to improve assisted or even spontaneous fertility outcome.