Changes in the incidence and clinical manifestations of herpes zoster

BACKGROUND: Shingles is the manifestation of activated latent disease caused by the varicella-Herpes Zoster virus. The prerequisite of its activation is a reduction of the immunity of the organism: the incidence (with some reservations) of herpes zoster in the population can be therefore considered an indicator of the general immune state. The objective of the submitted paper was to assess whether and to what extent the frequency of herpes zoster increased (whether the number of patients hospitalized at the Clinic for Infectious Diseases increased in 1974-1994, and if so, by how much). METHODS AND RESULTS: By comparing clinical manifestations of herpes zoster in a group of 348 patients hospitalized in 1992-1994 with results of a similar investigation made in the same department in a group of 308 patients hospitalized in 1979-1983 the following was revealed: the annual numbers of treated patients with herpes zoster doubled during the last 15 years. Almost 70% of the affected patients were then and now above 60 years of age, among the patients women predominated markedly (chi 2 = 69.540), the number of malignancies increased greatly (chi 2 = 4.435), there was also a significant increase of ischaemic heart disease, hypertension (chi 2 = 39.741) etc. As to the ratio of different sites of the Shingles , no significant changes were observed, while there was a significant increase of manifestations of dermal generalization (chi 2 = 36.377) and a significant increase of peripheral pareses (chi 2 = 5.615). The author explains the fact that the period of hospitalization was not longer and that there was even a significant decrease in the number of postherpetic neuralgias persisting for more than a month, by the early onset of treatment with Acyclovir administered by the i.v. route. CONCLUSIONS: The annual numbers of patients hospitalized on account of herpes zoster doubled during the past 15 years, the number of malignancies increased as well as the number of cardiovascular diseases, and the frequency of skin generalizations and peripheral pareses increased. Treatment with Acyclovir had a favourable effect on the period of hospitalization.

Glycoprotein D homologs in herpes simplex virus type 1, pseudorabies virus, and bovine herpes simplex virus type 1 bind directly to human HveC(nectin-1) with different affinities.

Distinct subsets of human receptors for alphaherpes viruses mediate the entry of herpes simplex virus (HSV), pseudorabies virus (PrV), or bovine herpes simplex virus type 1 (BHV-1) into cells. Glycoprotein D (gD) is essential for receptor-mediated entry of all three viruses into cells. However, the gD homologs of these viruses share only 22-33% amino acid identity. Several entry receptors for HSV have been identified. Two of these, HveA (HVEM) and HveC (nectin-1), mediate entry of most HSV-1 and HSV-2 strains and are bound directly by HSV gD. A third receptor, HveB (nectin-2), mediates entry of HSV-2 and only a limited number of HSV-1 strains. HveB and HveC can also serve as entry receptors for PrV, whereas only HveC can serve this function for BHV-1. We show here that gD from PrV and BHV-1 binds directly to the human receptors that mediate PrV and BHV-1 entry. We expressed soluble forms of PrV gD and BHV-1 gD using recombinant baculoviruses and purified each protein. Using ELISA, we detected direct binding of PrV gD to HveB and HveC and direct binding of BHV-1 gD to HveC. Biosensor analysis revealed that PrV gD had a 10-fold higher affinity than HSV-1 gD for human HveC. In contrast, the binding of BHV-1 gD to HveC was weak. PrV gD and HSV-1 gD competed for binding to the V domain of HveC and both inhibited entry of the homologous and heterologous viruses. These data suggest that the two forms of gD bind to a common region on human HveC despite their low amino acid similarity. Based on affinities for human HveC, we predict a porcine HveC homolog may be important for PrV infection in its natural host, whereas a BHV-1 infection in its natural host may be mediated by a receptor other than a bovine HveC homolog. Copyright 2001 Academic Press.

Infection concomitant with pediatric renal allograft rejection.

Renal allograft rejection episodes are frequent in children and often lead to allograft failure. Frequent association of fever with rejection in our transplant program provoked a prospective evaluation of concurrent infection during rejection episodes. Because cytomegalovirus has an established role in rejection and allograft survival, evaluation of cytomegalovirus and other herpes simplex viruses (human simplex virus type 1, varicella, Epstein-Barr virus, and human herpes simplex virus type 6 [HHV-6]) was undertaken in addition to standard bacterial investigation. A total of 37 patients were followed over a 30-month period. Six of eight rejection episodes were associated with herpes simplex viruses (HHV-6, n = 6, and Epstein-Barr virus, n = 1). Three of the herpes-group-associated rejection episodes were treated with antiviral therapy in addition to pulse steroid treatment, with full recovery. The three patients with HHV-6-associated rejection episodes who were treated with pulse steroids, but no antiviral therapy, developed chronic allograft rejection. The recipient's response to allograft antigens may be influenced by concomitant herpes simplex infection, and specific antiviral therapy appears to be indicated when infection is confirmed in association with rejection. An antiviral treatment program coupled with modulation of standard antirejection immunotherapy has the potential to improve morbidity and mortality in the pediatric renal transplant population.

The acquisition of herpes simplex virus during pregnancy.

BACKGROUND: The acquisition of genital herpes simplex 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. METHODS: 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. RESULTS: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes simplex 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 simplex 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. CONCLUSIONS: 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 simplex and perinatal morbidity.

HSV-2 specific serology should be offered routinely to antenatal patients.

The most devastating consequence of genital herpes simplex is neonatal herpes. It is clear that the majority of newborns acquire their infection by contact with infected genital secretions during delivery from an asymptomatic mother who acquired a first episode of genital herpes simplex near the time of labour. Since the majority of cases of first episode genital herpes simplex during pregnancy are unrecognised, the prevention of neonatal transmission will depend upon the identification of the HSV serologically discordant couple and the institution of appropriate interventions by mid pregnancy. Therefore, the precis of this discussion paper is that universal HSV serological testing should be performed at the first prenatal visit. As a corollary, type specific HSV serology will need to be commercially available and relatively inexpensive. In any country, pregnant women and their partners represent a broad, cross section of sexually active adults. The vast majority present themselves to the health care system for care during their pregnancies which is a period of time in which the focus of care is primarily preventive and during which women are generally motivated and compliant. This is truly the 'golden opportunity' to identify patients already infected as well as those at risk for acquiring Genital Herpes. Information regarding genital herpes simplex and methods of preventing transmission to susceptible partners and newborn infants can easily be added to educational programmes which have already become an institution within prenatal care. Copyright 2000 John Wiley & Sons, Ltd.

Predictive value of quantitative PCR-based viral burden analysis for eight human herpes simplex viruses in pediatric solid organ transplant patients.

Human herpes simplex viruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. It was hypothesized that viral burden quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. Here we report the results of a 2-year prospective study of 27 pediatric solid organ (liver, kidney, or heart) transplant recipients in which multiple samples were analyzed for levels of all eight human herpes simplex viruses by internal calibration standard-polymerase chain reaction. Herpes Simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpes simplex virus were not detected in any of these samples. Human herpes simplex virus types 6 and 7 were detected in half of the patients, but were present at low levels, similar to those found in reference populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in 89% and 56% of the patients, respectively. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded clinical evidence of disease by several weeks. EBV viral burden was relatively high in the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpes simplex viruses, is an effective method for monitoring pediatric transplant patients for significant herpes simplex virus infection and response to therapy.

A synthetic peptide from a heptad repeat region of herpes simplex virus glycoprotein B inhibits virus replication.

Glycoprotein B (gB) is the most conserved glycoprotein of herpes simplex viruses and plays important roles in virus infectivity. Two intervening heptad repeat (HR) sequences were found in the C-terminal half of all herpes simplex virus gBs analysed. A synthetic peptide derived from the HR region (aa 477-510) of bovine herpes simplex virus type 1 (BoHV-1) gB was studied for its ability to inhibit virus replication. The peptide interfered with cell-to-cell spread and consistently inhibited replication of BoHV-1, with a 50 % effective concentration value (EC(50)) of 5 microM. Inhibition of replication was obtained not only with herpes simplex viruses including pseudorabies virus and herpes simplex virus type 1 but also partly with Newcastle disease virus. Possible mechanisms of membrane fusion inhibition by the peptide are discussed.

Neonatal herpes simplex in Denmark 1977-1991.

BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes simplex 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 simplex in Denmark and to evaluate the prevention practice. METHODS: All newborns with perinatal herpes simplex 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 simplex 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 simplex 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.

Detection of herpes simplex virus DNA in serum and oral secretions during acute recurrent Herpes Labialis.

Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which the virus may be present in the blood during a localized infection in otherwise healthy patients is still unknown. Literature on patterns of HSV shedding into the oral cavity at the prodromal stage of the disease, during recurrences, and also during asymptomatic periods is still lacking. The present study aims at the detection of HSV DNA in the serum and oral secretions during acute Herpes Labialis using a highly sensitive technique, the polymerase chain reaction (PCR). The study included 10 patients with acute Herpes Labialis and five healthy controls. Using PCR, herpes simplex virus DNA was detected in the serum of seven patients (70%) and in the saliva of nine patients (90%). One of the control cases showed positive HSV DNA in the saliva (20%). There was good statistical agreement between the presence of HSV DNA in the serum and saliva. Frequency of attacks, patient's age, and gender had no statistically significant effect on the presence of the virus in serum or in saliva. It is concluded that HSV viremia during attacks of recurrent herpes simplex is more frequent than previously appreciated.

Herpes zoster and HIV-1 infection in a rural Ugandan cohort.

OBJECTIVE: To compare the rates and clinical features of herpes zoster in HIV-positive and HIV-negative individuals in a cohort in rural Uganda; to report the incidence of herpes zoster in the HIV-positive group in relation to seroconversion and CD4 cell counts and to determine whether it is indicative of a more rapid progression to death. DESIGN: A prospective population-based cohort. METHODS: The cohort comprised 107 prevalent and 144 incident (with documented dates of seroconversion) participants with HIV infection and 231 HIV-negative controls who were reviewed routinely every 3 months. RESULTS: The mean rate of herpes zoster was 53.6/1000 person-years in HIV-positive and 4.4 in HIV-negative participants. The cumulative incidence of a first episode of herpes zoster was 7.6% at 2 years, 12.6% at 4 years and 24.0% at 6 years after seroconversion; the incidence rate was 35.6/1000 person-years. There was no evidence of a significant effect of age, gender, period from seroconversion or CD4 cell count on this incidence rate. Herpes zoster was an indicator of HIV-1 infection in this population but not an indicator of more rapid progression to death after adjusting for CD4 cell count and age. CONCLUSIONS: The rates, including the cumulative incidence after seroconversion and the clinical presentation of herpes zoster, were similar to those reported from industrialized countries. Although an indicator of HIV-1 infection in this population, herpes zoster was unrelated to CD4 cell count or period from seroconversion and did not lead to a faster disease progression.