Neonatal Herpes Simplex Virus Infection Research Articles

Coexistence of Incontinentia Pigmenti and Neonatal Herpes Simplex Virus Infection

Abstract: We present a female infant with classic clinical and histologic features of stage I incontinentia pigmenti with coexistent neonatal herpes simplex virus infection. The diagnosis of a heritable cutaneous condition does not exclude the possibility of a coexistent infection and, given the similar clinical presentation of neonatal vesicular eruptions, accurate diagnoses may require skin biopsy and culture.

Herpes simplex viruses.

Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.

Neonatal herpes simplex virus infections

Neonatal herpes simplex virus (HSV) infection is one of the life-threatening infections of newborns. It affects approximately 1,500 to 2,200 infants per year in the United States. Changes in the presentation of neonatal HSV infection over the past two decades include an increase in the frequency of skin, eye, and mouth (SEM) disease with a relatively unchanged rate of central nervous system (CNS) disease, but a relative decline in disseminated infection. Although the mortality of neonatal HSV infections has declined with current antiviral therapy, the mortality rate in CNS disease (15%) and disseminated disease (57%) remains high. Morbidity has been seen most frequently in infants with CNS and disseminated disease, with seizures or infection with HSV-2 determined to be risk factors for poor outcome in survivors. In a multicenter, randomized, blinded study by the Collaborative Antiviral Study Group, no differences in outcome were seen between neonates treated with vidarabine and acyclovir. More recently, administration of oral acyclovir has been demonstrated to prevent cutaneous recurrences of HSV after neonatal SEM disease. Although promising, this investigational protocol requires further evaluation before a routine recommendation for prophylactic therapy with oral acyclovir can be made. The application of polymerase chain reaction to rapid diagnosis of neonatal HSV disease may provide additional information on which clinical decisions may be based, but its diagnostic utility outside the research setting is still unproven. Further clinical trials for prophylaxis of recurrent SEM disease, prophylactic therapy for the prevention of recurrences of CNS or disseminated disease, the appropriate use of rapid diagnostic testing, and future therapies that may include passive antibody plus antiviral therapy or higher dosage and longer duration of antiviral therapy need to be evaluated.

Neonatal herpes simplex virus infection in the British Isles

Summary. This study was set up to estimate the incidence of neonatal herpes simplex virus (HSV) infection in the British Isles, and to document the outcome of neonatal infection. Paediatricians reported cases of neonatal HSV through the active reporting scheme of the British Paediatric Association Surveillance Unit. Over a 5half year period (1986-91) 76 infants with neonatal HSV infection were reported, an incidence of recognised infection in the British Isles of 1.65/100000 livebirths. Twenty-five infants had HSV-1 infection, 24 HSV-2 and in 27 virus type was unknown. Twenty-seven had disseminated infection, 23 herpes encephalitis and 26 localised infection. Nineteen infants (25%) died in the neonatal period, and a further 25 (33%) have subsequently died or have long-term sequelae. At least half of the infants had been discharged home before symptoms became apparent. For 21 women there was evidence of a maternal genital herpes infection at some time, but this was reported or diagnosed retrospectively after neonatal HSV was suspected in 19 cases, and ante-natally in only two. Neonatal HSV is rare in the British Isles and routine antenatal screening for genital herpes infection during pregnancy is not justified. A high proportion of infected infants present with non-specific signs and symptoms and without mucocutaneous involvement; furthermore, there is rarely a history of maternal infection. As early diagnosis and prompt treatment is essential, there must be a high level of awareness of the serious nature of neonatal HSV infection.

The Acquisition of Herpes Simplex Virus during Pregnancy

The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied. We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections. Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died. Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.

Distinguishing vesicular and pustular disorders in the neonate.

Vesicular and pustular disorders are common in the neonatal period. Most are benign, but several serious infectious and noninfectious diseases can present in the neonate. This review focuses on the clinical features of these disorders as well as recent advances in the field. The following diseases are discussed: erythema toxicum, transient neonatal pustular melanosis, miliaria, neonatal acne, eosinophilic folliculitis, mastocytosis, acropustulosis of infancy, incontinentia pigmenti, scabies, neonatal and congenital candidiasis, syphilis, neonatal herpes simplex infections, neonatal varicella, and staphylococcal infections.

Neonatal Herpes Simplex Virus Infection

The incidence of genital herpes simplex virus (HSV) and neonatal HSV infection is increasing in the United States. The risk to the neonate of a woman with genital recurrences (1%-3%) versus first-episode infection (30%-50%), even when asymptomatic, has been defined. Appreciation of the subtle clinical signs, as well as more obvious cutaneous signs of neonatal infection, will lead to appropriate diagnostic evaluation (including, at times, polymerase chain-reaction assay) and therapy. Understanding the immune defects predisposing the neonate to severe HSV infection will enhance efforts to reconstitute the neonate's immune function. Maternal vaccination, chemoprophylaxis, and appropriate use of cesarean-section delivery may prevent cases of neonatal herpes now and in the future.

Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR). Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection. HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment. Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality. Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven.

Neonatal herpes simplex virus infection in the British Isles.

This study was set up to estimate the incidence of neonatal herpes simplex virus (HSV) infection in the British Isles, and to document the outcome of neonatal infection. Paediatricians reported cases of neonatal HSV through the active reporting scheme of the British Paediatric Association Surveillance Unit. Over a 5 1/2 year period (1986-91) 76 infants with neonatal HSV infection were reported, an incidence of recognised infection in the British Isles of 1.65/100000 livebirths. Twenty-five infants had HSV-1 infection, 24 HSV-2 and in 27 virus type was unknown. Twenty-seven had disseminated infection, 23 herpes encephalitis and 26 localised infection. Nineteen infants (25%) died in the neonatal period, and a further 25 (33%) have subsequently died or have long-term sequelae. At least half of the infants had been discharged home before symptoms became apparent. For 21 women there was evidence of a maternal genital herpes infection at some time, but this was reported or diagnosed retrospectively after neonatal HSV was suspected in 19 cases, and antenatally in only two. Neonatal HSV is rare in the British Isles and routine antenatal screening for genital herpes infection during pregnancy is not justified. A high proportion of infected infants present with non-specific signs and symptoms and without mucocutaneous involvement; furthermore, there is rarely a history of maternal infection. As early diagnosis and prompt treatment is essential, there must be a high level of awareness of the serious nature of neonatal HSV infection.

Prolonged presence of viral DNA in serum and CSF in neonatal herpes simplex virus infections

Prolonged presence of viral DNA in serum and CSF in neonatal herpes simplex virus infections

Effect of age and route of inoculation on outcome of neonatal herpes simplex virus infection in guinea pigs.

The morbidity and mortality of neonatal herpes simplex virus infection remains unacceptably high despite antiviral therapy. A better understanding of factors that might contribute to this poor outcome is needed but has been hindered by a lack of a good animal model. The recently described guinea pig model of neonatal HSV-2 infection was used to explore the effect of age and route of inoculation on the outcome of infection. After intranasal inoculation the onset, extent, and severity of the primary disease, as well as the number of recurrent lesion days, varied inversely with age. The route of inoculation also affected the outcome. Newborn animals were inoculated either intradermally on the scalp or by the intranasal, oral or corneal route. Animals inoculated on the scalp had the best outcome with no deaths or evidence of neurologic disease while the intranasal route produced the most severe disease, 88% mortality. Neurologic disease was common after oral (41%) and corneal (56%) inoculation but resolved spontaneously whereas following intranasal (39%) inoculation all animals with neurologic disease died. Recurrent disease manifest by cutaneous lesions was observed in all survivors of each group but also differed by the route of inoculation. The guinea pig model of neonatal HSV-2 disease appears to mimic human disease. The studies presented here show that the outcome of infection is influenced by the age and route of inoculation.

Effect of age and route of inoculation on outcome of neonatal herpes simplex virus infection in guinea pigs

Effect of age and route of inoculation on outcome of neonatal herpes simplex virus infection in guinea pigs

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a Phase I/II trial

Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Famciclovir: efficacy in zoster and issues in the assessment of pain.

When acyclovir was introduced in the early 1980’s, we saw a remarkable change in the treatment of herpes virus infections such as genital herpes simplex virus (HSV) infections, ocular HSV infections and varicella zoster virus (VZV) infections (chickenpox and shingles) in both the normal and immunocompromised host.1 The now widespread use of acyclovir is a reflection of its safety and tolerability, and clinical trial data has demonstrated its utility in the treatment of human disease. As a consequence, human suffering has been alleviated and, in some cases, mortality reduced (e.g., neonatal HSV infections and herpes simplex enciphalitis).2,3 KeywordsHerpes ZosterAcute PainAntimicrob AgentPostherpetic NeuralgiaRash OnsetThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Neonatal herpes simplex infection: Keys to early diagnosis

To highlight the clinical features of neonatal herpes simplex (HSV) infection that might facilitate earlier diagnosis. Fifteen year retrospective review of proven neonatal HSV cases from a regional neonatal referral unit. Fifteen cases reviewed: 10 with central nervous system (CNS) disease, three with skin, eyes or mouth (SEM) disease and two with disseminated disease (DIS). A median 4 day delay occurred between symptom onset and hospital admission. All cases presented after maternity hospital discharge, most commonly with feeding problems and lethargy. Six patients presented with skin lesions; parental genital herpes was reported in three (20%) cases. Seven infants died, four without acyclovir treatment and three of 11 treated cases. Three of five CNS disease survivors and all infants with SEM disease were normal at follow up. Acyclovir improves outcome in neonatal HSV infection. To improve outcome further earlier recognition of the non-specific presenting features of the disease is required.

Neonatal herpes simplex: clinical findings and outcome in relation to type of maternal infection

In 39 mothers of children with neonatal herpes simplex virus infection, maternal infection was serologically characterized retrospectively and was related to maternal clinical symptoms and to the clinical findings and outcome in the child. Thirteen mothers had a primary infection (six type 1, seven type 2), mostly with clinical symptoms. The mean age of onset of the disease of the infants was 7 days and a disseminated disease was most commonly found. Most of the type 1-infected children recovered completely, whereas all but one of the type 2-infected children died. Twenty mothers had a recurrent (2 type 1, 18 type 2) and 4 an intermediate infection (primary type 2, prior infection with type 1), mostly asymptomatic. Their children had a localized disease (of the skin-eye-mouth or the central nervous system) with onset at a mean age of 14 or 13 days, respectively. The frequency of neurological sequelae was high. Two mothers had no serological signs of herpes infection.

Genital herpes during pregnancy: No lesions, no cesarean

To determine the effects at our hospital of adoption of the 1988 guidelines recommended by ACOG for management of genital herpes infections during pregnancy. Between 1984-1986, 96 pregnancies complicated by active genital herpes were delivered at Parkland Hospital. The outcome of these pregnancies were compared with 217 similar pregnancies managed after implementation of the 1988 ACOG herpes guidelines. Adoption of the 1988 ACOG herpes guidelines resulted in a 37% decrease in the use of cesarean delivery for women with genital herpes infections at our hospital. Most of this decrease was because the new guidelines eliminated the need for a confirmatory negative herpes culture before permitting vaginal delivery. No neonatal herpes infections occurred as a result of implementing the ACOG recommendations. The rate of cesarean delivery for women with genital herpes infections during pregnancy declined significantly at our hospital as a result of the adoption of ACOG herpes guidelines, and there were no neonatal consequences, such as increased incidence of neonatal herpes simplex virus infection.

Liver Failure due to Disseminated HSV-1 Infection in a Newborn Twin

Most cases of neonatal herpes simplex virus (HSV) infection result from contact with maternal genital tract secretions and are caused by infections with HSV type 2. We report on a fatal HSV-1 infection in a newborn twin presenting with liver failure. The infection was acquired by single contact with an aunt. The route of transmission was proven by PCR followed by restriction endonuclease fingerprinting and DNA sequencing. This report demonstrates that liver failure may be an early and single symptom in life-threatening neonatal HSV-1 infection.

Neonatal herpes simplex virus infection: pathogenesis and treatment in the guinea pig.

Intranasal inoculation of newborn guinea pigs with herpes simplex virus (HSV) resulted in local skin-eye-mouth (SEM), central nervous system (CNS), and disseminated infections with high but not universal mortality. Cutaneous HSV inoculation produced self-limited SEM infection without evidence of CNS or disseminated disease. HSV infection of the upper respiratory tract of the newborn guinea pig resulted in early spread to the CNS and frequent viral dissemination. The outcome of infection was favorably affected by treatment with acyclovir. Spontaneous cutaneous recurrences occurred in most survivors. The newborn guinea pig should provide a useful model to explore both the pathophysiology and control of neonatal HSV infection.

Herpes simplex virus infections of women and their offspring: implications for a developed society.

Herpes simplex virus infections of humans have been known since ancient times. Contemporary society has witnessed a series of devastating manifestations of herpes simplex virus infections--namely, genital herpes simplex virus infection and neonatal herpes simplex virus infection. With the evolution of society, particularly advances in birth control and increasing promiscuity, the seroprevalence of herpes simplex virus type 2 infections has increased worldwide, however, more so in developed societies. As a consequence, individuals of child-bearing age are at risk for either reactivation of herpes simplex virus at termination of gestation or acquisition of a new primary infection at that time. The consequences of vertical transmission of herpes simplex virus from mother to child, resulting in neonatal herpes simplex virus infection, can be devastating. Current efforts, which are directed toward the treatment of neonatal herpes, have established the value of drugs such as vidarabine and acyclovir. However, the real emphasis for future programs is the prevention of herpes simplex virus infections to avoid person-to-person transmission either horizontally or vertically. The development of vaccines directed against herpes simplex virus may be of value toward this end.