Use of aciclovir in herpes simplex virus infections

Herpes simplex virus type 1 and type 2 cause a wide range of illnesses ranging from minor cold sores to severe necrotising encephalitis or disseminated systemic infections seen in immunocompromised patients including neonates. Following primary infection, the virus is not eradicated from the body but is latent in sensory nerve ganglia where it can reactivate and cause recurrent disease. Aciclovir is the most studied and used antiviral agent with activity against herpes simplex virus infections. In most situations the use of aciclovir shortens the duration of clinical illness and viral shedding and reduces morbidity and mortality. All life- or sight-threatening infections should be managed in an inpatient hospital setting with intravenous therapy. The use of oral aciclovir is recommended in patients with non-life-threatening illness who may still have significant symptoms.     

Viremia in neonatal herpes simplex virus infections.

BACKGROUND: Polymerase chain reaction assays of the peripheral blood mononuclear cells (PBMC) and plasma may facilitate the diagnosis of neonatal herpes simplex virus (HSV). METHODS: Assays for HSV DNA were submitted from at least 1 specimen site (PBMC, plasma or cerebrospinal fluid) in 11 consecutive cases of neonatal HSV infection. RESULTS: HSV DNA was detected by PCR in the PBMC of 6 of 10 infants tested (60%), the plasma of 4 of 6 tested (67%) and the cerebrospinal fluid of 4 of 11 tested (36%). CONCLUSIONS: HSV viremia is more frequent than previously appreciated, and detection of HSV DNA in PBMC and plasma is a useful diagnostic tool, particularly in infants without skin lesions.     

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.     

Prevention and management of neonatal herpes simplex virus infections

Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. All infants are potentially at risk for neonatal HSV infection. This position statement reviews epidemiology, transmission and risk factors, with a focus on intrapartum infection. It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. Recommendations for managing newborns known to have been exposed intrapartum to HSV are based on expert opinion because a randomized trial to compare management options is not feasible. Guidance is provided for the empirical management of infants with suspected clinical sepsis, including those who do not respond to antibacterial therapy. The present statement replaces a 2006 position statement by the Canadian Paediatric Society.     

A prospective evaluation of primary genital herpes simplex virus type 2 infections acquired during pregnancy

In order to study the epidemiology of herpes simplex type 2 (HSV-2) infections during pregnancy, we used an enzyme immunoassay to detect type-specific antibodies to HSV-2 glycoprotein G in serial blood samples obtained from a cohort of 1891 pregnant women. Blood samples obtained at about 17 and 32 weeks of gestation and at the time of delivery were assessed for antibody to HSV-2 glycoprotein G in order to evaluate the prevalence of past infections with HSV-2 and the rate of acquisition of HSV-2 infection during pregnancy. Three hundred eleven pregnant women (16.5%) were found to have had past infections with HSV-2. Four of the 1580 women who were initially seronegative developed antibodies to HSV-2 during pregnancy. The annualized rate of acquisition of HSV-2 infection in pregnant women was 0.58%. Three of four women had asymptomatic primary infections; all of the women had preexisting HSV-1 immunity. None of the women or their infants experienced any adverse consequences of gestational herpes. Based upon our very limited number of observations to date, asymptomatic primary episodes occurring in women with previous HSV-1 immunity may be of less consequence to the fetus and neonate than symptomatic true primary HSV-2 infections.     

Herpesviridae infections in newborns: varicella zoster virus, herpes simplex virus, and cytomegalovirus

Varicella zoster virus (VZV), herpes simplex virus (HSV) and cytomegalovirus (CMV) are all members of the Herpesviridae family.Humans are the only source of infection for these double stranded DNA viruses. Infants may acquire these infections in utero, peripartum, or postnatally, resulting in a variety of clinical syndromes, ranging from asymptomatic infection to severe infection,with high mortality rates and significant long-term morbidity.This article presents the epidemiology, clinical characteristics, treatment,and prevention strategies for VZV, HSV, and CMV infections in infants.     

A prospective study of parainfluenza virus type 4 infections in children attending daycare

Studies of parainfluenza virus type 4 (PIV-4) have been limited by difficulty in culturing. We prospectively studied a cohort of 225 young children attending daycare followed for 165 child-years, using polymerase chain reaction to detect 12 viruses, including PIV-4. PIV-4 was second only to PIV-3, occurring in 9 of 87 (10%) PIV+ illnesses. PIV-4 illnesses were not more severe and not associated with a specific clinical syndrome.     

Antibody response to herpes simplex virus type 1 polypeptides and glycoproteins in primary and recurrent infection

Sequential sera from a patient with primary Herpes Simplex Virus type I (HSV-1) encephalitis and a patient with HSV-1 recurrent oral lesions were collected. Sera were analyzed quantitatively by radioimmunoassay and qualitatively by electrophoresis and autoradiography of immune precipitates to determine the sequence of antibody production to specific radiolabeled HSV-1 polypeptide and glycoprotein antigens. The major antibody response in both primary and recurrent sera was against HSV-1 envelope antigens and the major capsid polypeptide. Sequential sera showed a significant correlation between neutralizing antibody titers and quantitative antibody to HSV-1 glycoproteins. Qualitative electrophoretic analysis of primary infection sera showed sequential appearance of antibodies to increasing numbers of HSV-1 polypeptides by the fourteenth day of infection. A corresponding qualitative antibody response to glycoproteins was not seen. Sequential sera obtained before, during, or after a recurrent lip lesion in another patient showed no significant quantitative or qualitative changes in antibodies to either HSV-1 glycoproteins or polypeptides.     

Clinical manifestations of primary herpes simplex virus type 1 infection in a closed community.

The clinical features and the molecular epidemiology of primary herpes simplex virus type 1 (HSV-1) infection among children younger than 3 years of age were investigated in day-care nursery. Serial sera were assayed for anti-HSV-1 glycoprotein B antibody by enzyme-linked immunosorbent assay. Serologic examinations revealed 55 cases of primary HSV infection during the observation period. Fifty-one of them (93%) had typical herpetic gingivostomatitis, showing a high rate of clinically overt infection. Four outbreaks of herpetic gingivostomatitis were observed during the observation period. Forty-one children were infected with HSV-1 in the outbreaks. The rates of infection in the susceptible children were 81%, 73%, 78%, and 100%, respectively, in the four outbreaks. Restriction endonuclease analysis of DNA of isolated HSV revealed that only one strain of HSV-1 had been transmitted among children for a long period.     

Brainstem involvement in neonatal herpes simplex virus type 2 encephalitis

Herpes simplex virus encephalitis in the newborn typically involves the cerebral cortex in a widespread manner. Herpes simplex virus type 2 rarely involves the brainstem. Here we report a 16-day-old infant with predominant brainstem and cerebellar involvement secondary to herpes simplex virus type 2 infection. Diffusion-weighted MRI performed 3 days after the onset of symptoms revealed restricted diffusion mainly in brainstem and cerebellar structures. No abnormal findings were seen on conventional MRI. Subsequent MRI scans showed evolution of the brain injury with extension along the corticospinal tracts. However, there was no evidence of any other supratentorial gray or white matter injury. This is the first report of predominant brainstem involvement in neonatal herpes simplex virus type 2 encephalitis. In addition, the importance of performing diffusion-weighted sequences to detect early central nervous system involvement and serial MRI to follow the evolution of central nervous system lesions is emphasized.     

Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum.

AIM: To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection. METHODS: Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR). RESULTS: In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19 (90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis. CONCLUSIONS: These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.