Herpes simplex virus infections in the neonate

Objectives: To review the experience of the Camperdown Children's Hospital with neonatal herpes simplex viral (HSV) infections between 1960 and 1992.
Design: A retrospective record review of all cases of HSV infection.
Results: Fifteen proven HSV infections were found. Only three cases had a definite history of HSV infection during pregnancy. Six were delivered at 36 weeks gestation or earlier. Seven weighed 2500 g or less. Forty-three per cent developed physical signs within 7 days of birth. Three cases were confined to skin, eyes and mouth, five were generalized, six had encephalitis with or without skin lesions, and one had pneumonitis. The mortality rate comprising the five with generalized infection was 47%, one with encephalitis and the one with pneumonitis. Four of the eight survivors have persisting neurological impairment. Those with disseminated infection and encephalitis did poorly regardless of antiviral treatment.
Conclusion A high index of suspicion of HSV infection is important so that antiviral treatment can be commenced early, particularly for those infections localized to skin, eye and mouth where there may be a good prognosis.     

Herpes simplex virus in childhood erythema multiforme.

Although an association between herpes simplex virus (HSV) infection and erythema multiforme (EM) minor has been documented in adults, this has not been reported in the pediatric population. This study assessed the potential role of HSV infection in the pathogenesis of EM minor in children. Erythema multiforme skin lesions from 20 children, aged 1 to 16 years, were examined for the presence of HSV by using the polymerase chain reaction. The children included all fit strict clinical criteria for EM minor. Ten had a clinical history of an antecedent herpes infection ("herpes-associated EM"), and 10 did not ("idiopathic EM"). Herpes simplex virus DNA was detected in skin lesions of 8 of 10 children with herpes-associated EM and in 8 of 10 with idiopathic EM. Control skin biopsies from children with other bullous inflammatory diseases were negative. In addition, no HSV could be detected in a biopsy of normal uninvolved skin of a child in whom HSV was present in lesional skin. In situ hybridization on selected biopsies by means of an HSV-specific riboprobe confirmed the presence of HSV and localized it to the epidermis. It is concluded that HSV is a significant precipitating factor for EM minor in children, as it is in adults, and that clinicians should maintain a high index of suspicion of HSV even in the absence of a known history of herpes infection.     

Herpes simplex encephalitis in childhood

This is a report on diagnostic and therapeutic experience in 6 patients aged 3 weeks to 6.3 years suffering from herpes simplex encephalitis. In 2 patients, a 3-week-old newborn and a 1.3-year-old boy, acyclovir-therapy started at days 8 and 17 respectively, following the demonstration of hemorrhagic necrosis in the brain by cranial CT-scan and IgM-specific HSV-antibodies in the blood. A 6.3-year-old girl was treated with acyclovir at day 10 of her illness, when cCT showed hemorrhagic necrosis in the brain. It was not before the 21st day, that diagnosis of HSE could be confirmed serologically. She suffered a relapse of encephalitis 5 weeks later. In a 3-month-old boy, treated with acyclovir at day 4 of his illness, IgM-specific HSV-antibodies were found already at day 4. His clinical course was complicated by subdural effusion. These 4 children survived with severe neurologic sequelae. Another 2 patients, a 5- and 7.5-month-old boy respectively, survived without apparent defect. In both cases vesicles upon the tongue appeared in the beginning of illness. Acyclovir-therapy started at day 7, diagnosis being confirmed serologically later. In our experience HSE should be suspected in children suffering from fever, drowsiness and focal or secondarily generalizing seizures. In these cases antiviral therapy should not depend on serologic findings.     

Herpes simplex virus type 1 infections presenting at birth

Two cases of intra-uterine acquired neonatal herpes simplex type I presented with atypical skin lesions apparent at or shortly after birth; the timing and appearance of the lesions meant that herpes virus infections were not considered to be the most likely diagnosis. Once herpes simplex was diagnosed, both infants were treated with acyclovir. Prompt diagnosis and institution of acyclovir are imperative for a favourable outcome from neonatal herpes infections.     

Herpes simplex virus infections of the central nervous system

Herpes simplex virus (HSV) infections of the central nervous system (CNS) can occur within weeks after birth (neonatal HSV disease) or in childhood or adulthood [herpes simplex encephalitis (HSE)]. Most cases of neonatal HSV disease are caused by HSV type 2, whereas virtually all cases of HSE are caused by HSV type 1. Diagnostic advances made during the past decade include the application of polymerase chain reaction (PCR) technology to cerebrospinal fluid from patients with suspected HSV CNS disease to evaluate for the presence of HSV DNA. Although not foolproof, PCR is a powerful diagnostic tool that has supplanted brain biopsy as the modality of choice for diagnosing HSV CNS disease, in no small part because of the invasiveness of brain biopsy. PCR also can provide information regarding the therapeutic response to antiviral therapy. Efforts made during the past decade to improve the outcome of HSV CNS disease have focused on increased doses of intravenous acyclovir administered for longer durations of time. Although advances have been achieved, morbidity and mortality rates from neonatal HSV disease and HSE remain unacceptably high.     

Herpes simplex viral pneumonitis in childhood

We report two cases of herpes simplex pneumonia in children. One patient had Down syndrome, and the other was immunosuppressed by cancer therapy. Both had interstitial pneumonitis with nonspecific physical, radiographic, and laboratory findings, and both died. The diagnosis of herpes simplex pneumonia was made by isolation of herpes simplex virus from autopsy lung cultures as well as by demonstration of antigen in the tissue with an immunoperoxidase procedure. Inasmuch as herpes simplex pneumonia is a potentially treatable infection, early virologic studies are recommended in immunocompromised children with progressive pneumonitis of undetermined cause.     

Herpes simplex virus infection

Herpes simplex virus (HSV) infections are among the infections most frequently encountered by humans. Two types of HSV infections have been identified-HSV-1, which usually causes orolabial disease, and HSV-2, which is associated more frequently with genital and newborn infections. Usually, HSV causes mild and self-limited disease of the mouth and lips or at genital sites. However, on occasion, the disease can be life-threatening. Such is the case with neonatal HSV infection and HSV infections of the central nervous system. Furthermore, in the immunocompromised host, severe infection has been encountered and is a source of morbidity. Even in the immunocompetent host, frequent recurrences, particularly those of the genital tract, can be debilitating. Because HSV does cause genital ulcerative disease, it is associated with an increased risk of acquiring a human immunodeficiency virus infection. During the past 2 decades, selective and specific inhibitors of HSV replication have been developed. These agents, acyclovir, valaciclovir, and famciclovir, all accelerate the events of healing and decrease the probability of excreting the virus when they are taken in a suppressive fashion. The long-term safety of acyclovir has been unequivocally established. Its prodrug, valaciclovir, and the prodrug of penciclovir, famciclovir, have not been used in practice as long and, therefore, less is known about these agents; however, neither is available as a pediatric formulation.     

Herpes simplex virus encephalitis during childhood: importance of brain biopsy diagnosis

Twelve consecutive pediatric patients 1 day to 11 years of age with suspected herpes simplex virus (HSV) encephalitis underwent brain biopsy. Five were proved to have HSV encephalitis; seven had subdural empyema, malignant glioma, enteroviral encephalitis, (one each), and presumed viral encephalitis, non-HSV (four). Neither epidemiologic, clinical, nor noninvasive laboratory tests were able to help differentiate the two groups of patients. The EEG was more sensitive than the CT scan in demonstrating focal lesions in early HSV encephalitis. In patients with HSV encephalitis, the mean time from hospital admission to appropriate antiviral chemotherapy was 3 days, and the outcome of HSV encephalitis was uniformly poor. In patients with febrile encephalitis-like syndromes with CSF pleocytosis, focal neurologic signs, or other localizing test results (EEG, CT), anticipatory antiviral chemotherapy and brain biopsy are the only hope to prevent the poor outcome associated with HSV encephalitis, to exclude other treatable conditions, and to avoid multiple types of unnecessary empiric therapies.     

Herpes simplex virus encephalitis in children

Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children. The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms. The CSF is abnormal in over 90 per cent of cases. The EEG, CT, and MRI will further help in detecting focal encephalitis. The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time. Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity. The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.     

Herpes simplex virus esophagitis in immunocompetent children

OBJECTIVES: To review clinical, laboratory, endoscopic and histologic features, treatment and outcome of immunocompetent children with Herpes simplex virus esophagitis. METHODS: Retrospective analysis of the medical records of six children (five males) referred to our unit between 1997-2001. RESULTS: The median age at presentation was 4 years. Fever was present in all, odynophagia/dysphagia in five, retrosternal pain in four, vomiting in three, drooling in two and irritability and drowsiness in one. The median time between the onset of symptoms and the diagnosis was 6.5 days. Endoscopy, performed in all, showed friable mucosa and erosive-ulcerative involvement, with histology showing inflammation and ulcerated esophagitis. Tissue viral culture was performed in five patients and was positive in three, and polymerase chain reaction was positive in two of four tested. Serology was consistent with primary Herpes simplex virus infection in all. All received nasogastric feeding and acyclovir. The outcome was very good. CONCLUSIONS: This is an uncommon and under-recognized condition in the immunocompetent child. The most common symptoms are sometimes not diagnostic, particularly in very young children. The presence of unusual clinical signs may lead to a difficult and delayed diagnosis. Treatment with acyclovir may have hastened the resolution of symptoms, but a controlled clinical study was not performed.     

Herpes simplex virus colitis in a neonate

Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life.     

Herpes simplex virus: fetal and decidual infection

We report 2 cases of probable in-utero transmission of herpes simplex virus. Herpes viral antigen was localized in these cases to the decidualized endometrium, using an immunoperoxidase staining technique. Routine histology did not show herpes inclusions in the decidual or glandular cells. This finding suggests that herpes virus may infect endometrial cells during pregnancy.