herpes
Herpes Simplex Virus in Children.

Whitley RJ.

Children's Hospital at the University of Alabama at Birmingham, 1600 7th Avenue, South, ACC 616, Birmingham, AL 35233, USA. rwhitley peds.uab.edu

Herpes simplex virus (HSV) infections are ubiquitous. Children are infected with HSV resulting in totally asymptomatic acquisition to life-threatening disease. Therapy of HSV diseases of children can be considered according to severity and time of acquisition. Neonatal herpes simplex virus infections take one of three forms--disease localized to skin, eye, or mouth (SEM), encephalitis, or multiorgan disseminated disease. Treatment consists of intravenous (IV) administration of acyclovir. Supportive care for patients with life-threatening disease is an integral component of patient management. Mucocutaneous HSV infections in the immunocompromised host can be treated with either intravenous acyclovir or one of the orally bioavailable antiviral therapies. For hospitalized patients, therapy consists of IV acyclovir at 5 mg/kg every 8 hours for 7 to 14 days. For ambulatory patients, therapy is tailored according to age. For children less than 12 years of age, oral acyclovir is administered at a dosage of 20 mg/kg every eight hours. Although no controlled studies have been performed with valaciclovir or famciclovir, the pharmacokinetics of these medications would suggest superiority over acyclovir. Dosage recommendations have not been established for young children. For postpubertal children, dosage should mirror that of adults. Valaciclovir is administered at 500 mg twice daily. Famciclovir is administered at 125 mg three times daily. Herpes simplex keratoconjunctivitis is treated with topical triflurothymidine. Two drops are applied to the infected eye five times daily until resolved. Recurrences are managed in a similar manner. Some physicians administer oral acyclovir at the doses noted above in order to prevent frequent recurrences. Genital HSV infections can be treated with acyclovir, valaciclovir, or famciclovir. Episodic treatment of recurrent episodes is usually not necessary in childhood. Importantly, all data on the use of these compounds for these conditions have been generated in adults. Physician judgment is required for the management of recurrent herpes labialis, erythema multiforme, and herpes gladitorum. No controlled studies have been performed in children, although experience with acyclovir, valaciclovir, and famciclovir have resulted in their use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11931730&dopt=Abstract herpes medicine



herpes
Concatemeric intermediates of equine herpes virus type 1 DNA replication contain frequent inversions of adjacent long segments of the viral genome.

Slobedman B, Simmons A.

Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, Australia.

In common with other alpha-herpes viruses, the genome of equine herpes virus type-1 (EHV-1) comprises covalently linked long and short unique sequences of DNA, each flanked by inverted repeats. Equimolar amounts of two genomic isomers, generated by free inversion of the short segment, relative to the long segment, are packaged into EHV-1 virions. In contrast with herpes simplex virus (HSV), inversion of genomic long segments has not been described. In the current work, the structures of high molecular weight intermediates of EHV-1 DNA replication were studied by field inversion gel electrophoresis. It is shown that adjacent long segments of the viral genome are frequently inverted in concatemeric intermediates of EHV-1 DNA replication. Further, like HSV concatemers, high molecular weight intermediates of EHV-1 replication are flanked exclusively by the long segment of the viral genome. Hence, despite the fact that only two, rather than four, isomers of EHV-1 DNA are packaged into virions, the intermediates of EHV-1 DNA replication closely resemble those of herpes simplex virus type 1 in structure. These data have implications relating to the mechanisms involved in packaging of alpha-herpes virus DNA.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9126253&dopt=Abstract herpes medicine



herpes
Histopathology of peripheral nerves in cutaneous herpes virus infection.

Worrell JT, Cockerell CJ.

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, USA.

Cutaneous herpes virus infection is a common viral disorder manifest by epidermal and/or mucosal vesicle formation. Though it is believed that the virus most likely resides in regional sensory ganglia following primary infection and that cutaneous involvement represents reactivation of a latent infection, the histopathology of cutaneous nerves in sites of disease has not been well characterized. In order to assess and characterize the pathologic changes of these nerves, we retrospectively examined 54 cases of cutaneous and mucosal herpes virus infection as defined by the presence of diagnostic multinucleate epithelial giant cells that demonstrated viral cytopathic effect. Dermal nerves were evaluable in 48 of 54 cases. All cases showed perineural inflammation that consisted of a dense mixed lymphocyte-polymorphonuclear cell infiltrate. Twenty-six cases exhibited intraneural infiltrations accompanied by Schwann cell hypertrophy with nuclear eosinophilia and pyknosis. Frank neuronal necrosis was present in 21 cases, with viral cytopathic effect evident within neurons of four cases. The degree of peri- and intraneural inflammation correlated with the severity of the inflammatory response within the dermis in most cases; however, in eight cases there was inflammatory involvement of neurovascular structures distant from and out of proportion to dermal and epidermal changes. Immunoperoxidase staining using a polyvalent antibody to human herpes virus was performed in two cases and demonstrated viral antigen within nerve twigs. This pattern of peripheral nerve twig inflammation, along with the occurrence of more distant neural involvement, may prove to have diagnostic implications and serve as a clue in the recognition of cutaneous herpes virus infection, particularly in cases with subtle or absent epidermal alteration. Furthermore, the presence of inflammation within and around nerves as well as degenerative changes suggest that nerve twigs are not passive conduits for viral spread but may be directly involved in infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9129697&dopt=Abstract herpes medicine



herpes
Genital herpes in a primary care clinic. Demographic and sexual correlates of herpes simplex type 2 infections.

Wald A, Koutsky L, Ashley RL, Corey L.

Department of Medicine, School of Medicine, University of Washington, Seattle 98144, USA.

BACKGROUND AND OBJECTIVES: Genital herpes remains one of the most prevalent sexually transmitted diseases (STDs). The sexual behavioral correlates of herpes simplex virus type 2 (HSV-2) infection in the general population have not been well characterized. GOALS: To assess demographic and sexual behavioral correlates of symptomatic and subclinical HSV-2 infection. STUDY DESIGN: Cross-sectional survey of 922 randomly chosen patients and 78 of their partners (1,000 total) in a family practice. Sexual behavior information was collected in 492 people. RESULTS: Two hundred twenty-five (23%) heterosexual people had HSV-2 infection, but only 59 (26%) reported a history of genital herpes. HSV-2 seroprevalence was 63% in African-American women, 27% in white women, 40% in African-American men, and 12% in white men. In multivariate analyses of risk factors for HSV-2 infection among men, 10 or more sexual partners and a prior STD were statistically significantly associated with HSV-2 infection. Among white women, number of sexual partners, a prior STD, marriage or cohabitation, and less than a college education were predictive of HSV-2 infection. A history of oral sex was the only statistically significant predictor of HSV-2 infection in African-American women. CONCLUSIONS: Risk factors for HSV-2 infection differ by gender and ethnic group. Traditionally recognized behavioral correlates of STD acquisition may not identify people in communities with high prevalence of HSV-2 infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9132981&dopt=Abstract herpes medicine



herpes
Bovine herpes virus 1 glycoprotein B does not productively interact with cell surface heparan sulfate in a pseudorabies virion background.

Klupp BG, Karger A, Mettenleiter TC.

Federal Research Centre for Virus Diseases of Animals, Insel Riems, Germany.

Attachment to cell surface heparan sulfate proteoglycans is the first step in infection by several alphaherpes viruses. This interaction is primarily mediated by virion glycoprotein C (gC). In herpes simplex virus, in the absence of the nonessential gC, heparan sulfate binding is effected by glycoprotein B. In contrast, gC-negative pseudorabies virus (PrV) infects target cells via a heparan sulfate-independent mechanism, indicating that PrV virion gB does not productively interact with heparan sulfate. To assay whether a heterologous alphaherpes virus gB protein will confer productive heparan sulfate binding on gC-negative PrV, gC was deleted from an infectious PrV recombinant, PrV-9112C2, which expresses bovine herpes virus 1 (BHV-1) gB instead of PrV gB. Our data show that gC-negative PrV-BHV-1 gB recombinant 9112C2-delta gCbeta was not inhibited in infection by soluble heparin, in contrast to the gC-positive parental strain. Similar results were obtained when wild-type BHV-1 was compared with a gC-negative BHV-1 mutant. Moreover, infection of cells proficient or deficient in heparan sulfate biosynthesis occurred with equal efficiency by PrV-9112C2-delta gCbeta, whereas heparan sulfate-positive cells showed an approximately fivefold higher plating efficiency than heparan sulfate-negative cells with the parental gC-positive virus. In summary, our data show that in a PrV gC-negative virion background, BHV-1 gB is not able to mediate infection by productive interaction with heparan sulfate, and they indicate the same lack of heparin interaction for BHV-1 gB in gC-negative BHV-1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9151882&dopt=Abstract herpes medicine



herpes
Genital herpes during pregnancy: inability to distinguish primary and recurrent infections clinically.

Hensleigh PA, Andrews WW, Brown Z, Greenspoon J, Yasukawa L, Prober CG.

Department of Obstetrics and Gynecology, Santa Clara Valley Medical Center, San Jose, California, USA.

OBJECTIVE: To determine if the signs and symptoms of genital herpes in pregnancy accurately identify primary genital herpes infections using serologic testing for final classification. METHODS: Twenty-three women with clinical signs and symptoms suggestive of primary genital herpes infections in the second and third trimesters of pregnancy were subsequently cultured and tested serologically (for herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and classified as having true primary (no herpes simplex virus type 1 or type 2 antibodies), nonprimary (heterologous herpes simplex virus antibodies present), or recurrent (homologous antibodies present) infections. RESULTS: Only one of 23 women with clinical illnesses consistent with primary genital herpes virus simplex infections had serologically-verified primary infection. This primary infection was caused by herpes simplex virus type 1. Three women had nonprimary type 2 infections, and 19 women had recurrent infections. Among culture-proven recurrent infections, 12 were caused by herpes simplex virus type 2 and three by herpes simplex virus type 1. Only one infant was born preterm, and no clinically significant perinatal morbidity was observed. CONCLUSION: Correct classification of gestational genital herpes infections can be accomplished only when clinical evaluation is correlated with viral isolation and serologic testing using a type-specific assay. Severe first episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not usually primary infections and are not commonly associated with perinatal morbidity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9170460&dopt=Abstract herpes medicine



herpes
Neonatal herpes in Denmark 1977-1991.

Fonnest G, de la Fuente Fonnest I, Weber T.

Department of Obstetrics & Gynaecology, Hvidovre Hospital, University of Copenhagen, Denmark.

BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes infection are still delivered by Cesarean section. This policy is currently being debated. The aim of this study was to determine the incidence of neonatal herpes in Denmark and to evaluate the prevention practice. METHODS: All newborns with perinatal herpes in Denmark 1977-1991 were identified from hospital-records. RESULTS: Of 862,298 deliveries 136 possible cases were found but only 30 (22%) fulfilled the criteria for neonatal herpes. The incidence increased from 2.36 to 4.56 per 100,000 live births during 1977-1984 through 1984-1991. Three mothers (10%) had recurrent herpes at delivery, three (10%) had primary herpes, and five (17%) had oral herpes. Seven infants (23%) were delivered by Cesarean section. Nine (30%) only had cutaneous herpes, four (13%) had CNS herpes, nine (30%) had disseminated disease. Six (20%) did not have any sequelae. Four (13%) died. Six (20%) had serious neurological sequelae. Seven (23%) only had cutaneous recurrences. In seven cases (23%) information was insufficient. CONCLUSIONS: During a 15 year period in Denmark only one neonate had serious sequelae following a recognized maternal herpes recurrence. Four infants had a serious infection in spite of Cesarean section. This study does not support a policy of Cesarean section in case of maternal recurrent herpes simplex infection at delivery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9174431&dopt=Abstract herpes medicine



herpes
The sequelae of herpes zoster.

Galil K, Choo PW, Donahue JG, Platt R.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass, USA.

BACKGROUND: The last 40 years was a period during which the incidence of herpes zoster appears to have increased substantially. OBJECTIVE: To determine whether the risk of complications of herpes zoster has changed during the last 40 years. METHODS: The automated medical records of a health maintenance organization were screened for diagnosis codes suggesting herpes zoster and potentially complicated cases of zoster. The predictive value of a herpes zoster diagnosis was calculated from sampling full-text records. Records of all patients with codes suggesting complications were reviewed in full. RESULTS: Of 859 individuals with herpes zoster who met the eligibility criteria, 101 were identified who experienced at least 1 complication, corresponding to a 60-day risk of 12%. Corrected for the sensitivity of the complication-finding strategy, the risk estimate was 14%. Risk increased markedly with age, with those older than 64 years having more than 6 times the risk of complications of those younger than 25 years (odds ratio, 8.3; 95% confidence interval, 2.5-29.3). Trigeminal distribution of rash and the presence of certain conditions associated with immune compromise appeared to increase risk. CONCLUSIONS: The apparent increase in the incidence of herpes zoster was not accompanied by a change in the risk of specific or overall complications in a population-based sample. Advanced age and other conditions associated with waning cellular immunity may confer an increased risk of experiencing a complicated course of herpes zoster.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9183232&dopt=Abstract herpes medicine