Intrauterine Herpes Simplex Virus Infection Research Articles

Heterogeneous cutaneous findings associated with intrauterine HSV infection: A case series and literature review.

Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.

No footprint too small: case of intrauterine herpes simplex virus infection

Abstract Objectives To describe the case of a preterm infant with intrauterine HSV infection. To discuss the epidemiology, features and complications associated with intrauterine HSV infection by conducting a review of medical literature. Case presentation A preterm male infant was born with diffuse skin erosions in various stages of healing suggestive of denuded bullae. Prenatal ultrasound showed evolving fetal cerebral ventriculomegaly, suspected Dandy-Walker malformation, and oligohydramnios. Neonatal skin swabs were positive for herpes simplex virus type 2 by polymerase chain reaction and the patient was treated with intravenous acyclovir from birth. Cranial ultrasound and magnetic resonance imaging findings showed severe progressive ex-vacuo ventricular dilatation consistent with intrauterine herpes simplex infection. Due to those findings and progressive multi-organ dysfunction, care was redirected to a palliative path and the child expired at 21 days of age. In retrospect, the mother had a few atypical vesicles on the left hand 4–5 weeks prior to delivery with a presumptive diagnosis of pompholyx. Conclusions Although confirmed intrauterine herpes simplex virus (HSV) infections are very rare, the potentially devastating prognosis and complications as evidenced by our case show that awareness of intrauterine HSV is critical for pediatricians as well as physicians involved in antenatal care. In order to adequately assess, treat and counsel pregnant women, more work is required to detect HSV infection, evaluate possible congenital infection and improve outcomes with fetal and neonatal treatment.

Intrauterine herpes simplex virus type one infection presenting with skin erosions and ulcers: Masking as neonatal sepsis

Neonatal infection with herpes simplex virus (HSV) either type 1 or type 2 can be acquired in utero, intrapartum, and postnatally. We report a case of intrauterine HSV type 1 infection with atypical cutaneous manifestations, misdiagnosed initially as neonatal sepsis. A high index of suspicion with diverse cutaneous manifestations kept in mind is necessary to diagnose infants with intrauterine HSV infection.

Intrauterine Herpes Simplex Virus Infection in a Monochorionic Twin Gestation.

Herpes simplex virus (HSV) of the newborn affects 1 in 3200 [1] live births in the United States, and can be acquired by the intrauterine or intrapartum route, or postnatally. Intrauterine or congenital infection represents the rarest form (5% of cases) [2] and frequently has devastating consequences such as congenital brain malformation and severe neurocognitive impairment leading to fetal or neonatal death [3]. Here we present two cases of fatal intrauterine HSV infection in monochorionic twin infants. CASE A 21-year-old secundigravida mother with twin gestation of 26-4/7 weeks presented with spontaneous rupture of membranes of clear amniotic fluid 11 hours prior to delivery. She had negative prenatal laboratory studies for hepatitis B, syphilis, human immunodeficiency virus (HIV), and an unknown group B streptococcus status. Her sexually transmitted infection history included chlamydia trachomatis infection treated during early pregnancy and no history of HSV in herself or her sexual partner. A structural survey 1 week prior to delivery revealed severe hydrops and hydranencephaly in the first twin, and moderate hydrocephalus in the second twin. The mother was afebrile, well-appearing, and reported no history of recent illness or genital lesions before or during either of her pregnancies. Both mother and father refused HSV serologic testing. The first twin boy was delivered via cesarean section with Apgar scores of 1, 2, and 3, at 1, 5, and 10 minutes, respectively. The infant was apneic, unresponsive to resuscitation efforts, and died shortly after birth. On autopsy, gestation was shown to be monochorionic–monoamniotic, and the placenta had evidence of acute chorioamnionitis; however, it was not tested for the presence of HSV. The intracranial cavity was composed of hemorrhagic fluid and fragments of parenchymal tissue with extensive necrosis and chronic inflammation, consistent with meningoencephalitis, and the liver was calcified and necrotic. Viral immunostaining revealed the presence of HSV in the adrenal gland and brain parenchyma, and no virus was detected in the liver. No viral cultures were performed on autopsy tissue due to formalin fixation, and surface cultures for HSV were not performed. The second twin boy had Apgar scores of 5, 7, and 8 at 1, 5, and 10 minutes, respectively. He was immediately intubated for respiratory distress, received inotropes and intravenous fluids for hypotension, and was given ampicillin and gentamicin for presumed sepsis. At 5 hours of life, vesicular skin lesions on the neck were noted on physical examination (PE). PE was otherwise unremarkable. HSV studies were sent from the skin lesion (neck), mucosal surfaces (eyes, mouth, rectum), and cerebrospinal fluid (CSF), and empiric acyclovir 20 mg/kg every 8 hours was started. Initial white blood cell (WBC) count, platelet count, liver function, and serum electrolytes were normal. The CSF revealed 111 WBC/mm 3 with a lymphocytic predominance, 7600 red blood cells/mm 3 , protein 1245 mg/dL, and glucose 21 mg/dL. Blood and CSF bacterial cultures were sterile. Toxoplasma immunoglobulin M antibody, cytomegalovirus (CMV), and parvovirus B-19 polymerase chain reaction (PCR) yielded negative results. PCR was positive for HSV type 2 (HSV-2) and negative for HSV type l from all five tested sites.

Intrauterine Herpes Simplex Virus Infection Presenting with Hypopigmented Lesions

Genital herpes simplex virus (HSV) is a sexually transmitted infection that can be transmitted from mother to child in utero, perinatally, or postnatally. Cutaneous infection with HSV commonly presents as vesicles affecting the skin, eyes, or mouth. In our case, we report a well child with cutaneous hypopigmented patches at birth that preceded typical blistering.

Neurologic Complications of Intrauterine Herpes Simplex Virus Infection

Three case reports of intrauterine herpes simplex virus infection (HSV) and 61 cases published between 1963 and 2009 are reviewed by researchers at Baylor College of Medicine, Houston, TX.

A Report of Three Cases and Review of Intrauterine Herpes Simplex Virus Infection

intrauterine herpes simplex virus (HSV) infection often is omitted from descriptions of neonatal HSV disease. Previous characterizations of intrauterine HSV infection limit manifestations to the triad of cutaneous, central nervous system (CNS), and ophthalmologic findings. We report 3 cases of intrauterine HSV infection and provide a contemporary literature review of this disease. cases published between 1963 and January 2009 were identified. Selected cases fit the clinical description of intrauterine HSV infection, had manifestations present at birth, and had virologic confirmation of infection. this review yielded 64 cases, 3 of which were our own, of intrauterine HSV infection. Less than one-third fit the typical triad. Of the patients with cutaneous findings at birth, 24 (44%) had manifestations other than vesicles or bullae. Confirmation of HSV infection by culture of cutaneous lesions present at birth was delayed beyond 72 hours after birth in 15 patients and occurred at a median of 10 days of age. Nine of these patients had lesions at birth that were neither vesicles nor bullae, and 14 cases were confirmed by culture of new vesicles. more than two-thirds of reported cases do not present with the typical triad. Cutaneous findings are not limited to vesicles or bullae. A high index of suspicion and recognition of varied cutaneous manifestations is necessary to diagnose infants with intrauterine HSV infection.

Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 1: Herpes simplex virus infections

Primary herpes simplex virus (HSV) infection may lead to severe illness in pregnancy and may be associated with transplacental virus transmission and fetal infection. The consequences may be abortion, stillbirth and congenital malformations. In neonates, the clinical findings after intrauterine HSV infection are characterized by skin lesions, diseases of the eye and neurologic damage. Herpes genitalis of pregnant women at the time of labor may result in life-threatening neonatal herpes. Currently, neither active nor passive immunization is available to prevent HSV infections during pregnancy and in the newborn infant. Therefore, antiviral treatment using aciclovir and/or valaciclovir must be considered in all primary episodes of genital herpes as well as in neonates who show signs of either infection. Clinical herpes lesions of the genitalia and/or positive test for virus detection at the time of delivery are an indication for cesarean section. However, this surgical intervention may be reduced by suppressive treatment of recurrent genital herpes with aciclovir or valaciclovir.

Major brain lesions by intrauterine herpes simplex virus infection: MRI contribution

The majority of neonatal Herpes Simplex Virus (HSV) infections are acquired at birth as a consequence of direct fetal contact with the infected birth canal or through an ascending infection after premature rupture of the amniotic membranes. Intrauterine transmission of HSV infection from mother to the fetus is rare; in only 5% of the cases it occurs from haematogenous transplacental dissemination. We present a case of transplacental intrauterine HSV infection after a primary maternal HSV infection in the first trimester of pregnancy. The diagnosis was assessed by viral culture and serologic tests. Ultrasound imaging revealed fetal brain damage in the third trimester. Finally, the MRI showed the devastating extensiveness of the HSV infection, which was beyond the expectation based on the ultrasound images.

Maternal herpes labialis in pregnancy and neural tube defects

According to previous case reports, some congenital abnormalities (CAs) of the brain, such as microcephaly, are a result of intrauterine herpes simplex virus infection. A population-based case-control study was conducted to determine the risk of neural tube defects (NTDs) after maternal herpes labialis infection during pregnancy. Data were taken from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, which included 1202 children with NTDs and 21641 comparison children with CAs other than NTDs. The adjusted relative risks (odds ratio [OR]) for NTDs associated with maternal herpes labialis in the first trimester of pregnancy was OR 1.19 (95% confidence interval [CI] 0.68-2.06), and in the entire pregnancy was OR 0.94 (95% CI 0.61-1.44). Self-reported maternal herpes labialis during pregnancy was not associated with a substantially increased risk of NTDs in infants.

Segmental scarring following intrauterine herpes simplex virus infection

We report the case of a female infant with an intrauterine herpes simplex type II infection in zosteriform distribution. She was treated with several courses of intravenous acyclovir leading to healing of the skin with segmental scarring. This patient is unusual in that the infection occurred in zosteriform distribution without any evidence of systemic involvement.

High interferon alpha levels in placenta, maternal, and cord blood suggest a protective effect against intrauterine herpes simplex virus infection.

Interferons (IFN) are produced by the placenta during pregnancy, and they can be detected in the maternal and fetal blood. Although the antiviral potential of IFNs is well established, it remains unclear whether the IFNs associated with pregnancy can prevent transplacental spread of viral infection. The present study was undertaken in order to determine the possible protective effect of placentally produced IFN-alpha on fetal acquisition of herpes simplex virus (HSV). Nine mothers with a known history of genital HSV infection were studied. In five cases IFN-alpha was detected in the placenta, maternal, and fetal blood, whereas in three cases IFN-alpha could not be detected. in the remaining case, IFN-alpha was found only in the maternal blood. As corroborated by the serological evidence of early HSV infection in the cord blood, the single case of vertical HSV transmission was observed in the group of IFN nonproducers. Furthermore, virus transmission did not occur in cases where IFN-alpha was present in the placenta and simultaneously in the maternal and fetal circulations. Thus, the present data indicate that high levels of IFN during pregnancy may protect the fetus from acquiring a possibly fatal intrauterine HSV infection.

Segmental scarring following intrauterine herpes simplex virus infection

Segmental scarring following intrauterine herpes simplex virus infection

Placental examination in intrauterine coinfection with herpes simplex virus and cytomegalovirus.

Intrauterine coinfections have rarely been reported. However, pregnancies exposed to multiple sexually transmitted infectious agents and drugs are likely to occur with increasing frequency and lead to complex pathology in the newborn. Often it will be difficult to establish a diagnosis, above all when this has to be done retrospectively. A premature (34 weeks) newborn presented with a complex clinical picture after exposure to multiple infectious and noninfectious teratogens during gestation. Immunocytochemical staining of the placental membranes and parenchyma suggested intrauterine coinfection by herpes simplex virus (HSV) type 2 and cytomegalovirus. This case illustrates the importance of careful placental investigation with modern techniques for the diagnosis of intrauterine HSV infection and coinfections.

Herpes simplex virus infection of cultured human term trophoblast.

Mononuclear trophoblast cells were isolated from term placentas of uncomplicated pregnancies, purified to homogeneity by negative immunomagnetic separation using monoclonal antibodies to the major histocompatibility complex, and challenged with herpes simplex virus (HSV). The cultures were highly susceptible to virus-induced cytopathic effect as evidenced by cytopathic alteration and inhibition of human chorionic gonadotropin (hCG) secretion. Both HSV I and II underwent a full replicative cycle in the trophoblast, although the production of progeny virus was 10-100 times less than that obtained with placental fibroblasts or choriocarcinoma cells. The permissiveness was independent of in vitro syncytial differentiation of the trophoblast. The results suggest that the trophoblast layer may be involved in intrauterine HSV infection.

Intrauterine herpes simplex virus infection.

Neonatal herpes simplex virus (HSV) infection usually is the consequence of intrapartum infection, with disease onset between 5 and 15 days of life. More recently, intrauterine HSV infection has been identified. Intrauterine infection is apparent within the first 24-48 hr of life and is associated with skin vesicles/scarring, chorioretinitis, and/or hydraencephaly. The recognition that babies with these findings can have disease caused by HSV should prompt enhanced physician awareness in the evaluation of newborns with suspected intrauterine infection. The frequency of intrauterine infection appears to be about 5% of all babies with neonatal HSV infection.

Intrauterine herpes simplex virus infections

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.

Intrauterine herpes simplex infection resembling mechanobullous disease in a newborn infant

We present a case of transplacentally acquired intrauterine herpes simplex virus infection in a newborn delivered at 36 weeks' gestation by cesarean section because of intrauterine growth retardation and maternal preeclampsia. The mother experienced a single episode of serotype 2 herpes progenitalis at 14 weeks' gestation. At birth the infant manifested clinical findings of herpes simplex virus infection, which resembled epidermolysis bullosa and aplasia cutis congenita. Preexisting cutaneous lesions and intact fetal membranes at delivery strongly support a transplacentally acquired intrauterine herpes simplex virus infection. Repeated Tzanck smears, viral cultures, and immunohistochemical studies of the skin were required to confirm the diagnosis. Intrauterine herpes simplex virus infection is associated with significant morbidity and mortality but responds to antiviral therapy. Therefore this diagnosis must be considered in the neonate born with bullous or eroded skin lesions.

INAPPARENT INTRAUTERINE HSV INFECTION DETECTED BY IMMUNOHISTOCHEMISTRY

We have used glucose oxidate-avidin-biotin (GAB) immunohistochemistry to detect herpes simplex virus (HSV) 1 & 2 virion antigen in fixed tissue. Cases were selected by placental or cord pathology &/or clinical findings in the fetus/neonate. Virus was detected in placenta, umbilical cord &/or fetal/infant organs from 17 pregnancies (1 set twins; 15 newborns & 3 stillborns). Antigen was found in single mesenchymal & epithelial cells without characteristic viral cytopathology. Viral cultures were positive in one case (skin vesicles). Five mothers had clinical or laboratory evidence of HSV 1/2 infections before or during pregnancy, but none had evidence of active infection at delivery. Thirteen pregnancies ended prematurely & 5 infants/fetuses were small for gestational age. Ten newborns were severely ill. Four infants died before 7-1/2 months of age. Of 11 survivors, 2 have severe CNS abnormalities, 1 persistent pulmonary disease & 2 remain hospitalized. Diagnoses associated with GAB positive herpes virus in specific organs include NEC, hepatitis with cholestatic jaundice, interstitial pneumonitis, aseptic meningitis, progressive cystic brain degeneration, & cardiac arrhythmias. We conclude that intrauterine HSV infection is more common than believed & that intrauterine HSV infection may persist in the fetus & neonate chronically without cytopathology or detectable virus & may be associated with prematurity, intrauterine & neonatal death, organ damage, & progressive neonatal disease.