Incidence of herpes simplex virus types 1 and 2 isolated in patients with herpes genitalis in Sheffield

Thirty-one strains of herpesvirus (HSV), isolated from patients presenting with the clinical features of herpes genitalis, were typed by polypeptide analysis of virus proteins in sodium dodecyl sulphate polyacrylamide gels. Nineteen (61.3%) of the isolates were shown to be HSV type 1 and 12 (38.7%) HSV type 2. There was no obvious difference in the incidence of HSV-1 in primary or recurrent infections and no apparent correlation between the genital site of isolation and virus type. The high incidence of genital HSV-1 infection in this group of patients is probably due to the increased practice of oro-genital contact and has possible implications for the future development of drugs and vaccines in the control of genital herpes.     

Incidence of herpes genitalis in Northern Ireland in 1973-83 and herpes simplex types 1 and 2 isolated in 1982-4.

During 1973 - 83 there was a pronounced rise in the number of new cases of herpes genitalis in Northern Ireland. This study of 127 patients with herpes genitalis shows that 30% had herpes simplex virus type 1 (HSV 1) and 70% had herpes simplex virus type 2 (HSV 2) infections. Of 41 sexual contacts who attended, only seven had herpes genitalis (caused in each case by HSV 2); another patient had a history of genital lesions, and one other of oral lesions, but HSV was not isolated from either patient. None of the other sexual contacts had a history of oral or genital infection. Of 31 women with herpes genitalis who consented to undergoing cervical cytology, five had atypical changes (all had primary herpes genitalis). Of these, four were infected with HSV 1 and one with HSV 2.     

Sequential genital infections with herpes simplex virus types 1 and 2.

Herpes simplex virus (HSV) types 1 and 2, typed by an enzyme linked immunosorbent assay (ELISA), were isolated at different clinical episodes from five people with genital herpes. This finding has important implications for assessing resistance to antiviral drugs in therapeutic studies.     

Recurrent male herpes genitalis with two different strains of herpes simplex virus type 2

A case of a 50-year-old man with recurrent herpes genitalis with two different isolated strains of herpes simplex virus (HSV) type 2 is reported. Morphologically, two types of cytopathic effects (CPE) induced by viruses were observed in the Vero cell cultures, one being a syncytial giant cell formation and the other a rounded cell formation without cell adhesion resembling the CPE induced by ordinary HSV type 2. In this case, it is clinically interesting that the patient complained of persistent pain on the glans and urethra without recurrence of herpetic lesions even after the involution of enanthema. The correlation between the persistent pain and neurovirulence of the two different HSV strains is discussed.     

Persistence of herpes simplex virus types 1 and 2 in infected individuals.

During a 23-month period, 18 patients with facial or genital herpetic lesions were examined; culture specimens from each patient were obtained three times per week for virologic studies. The isolated viruses were identified, and the average duration of herpesvirus in lesions was determined. Herpes simplex virus type 1 (HSV-1) was isolated from facial lesions for a mean duration of 3 1/2 days. In contrast, herpes simplex virus type 2 (HSV-2) was isolated from genital lesions for a mean duration of 5 1/2 days. The duration of viral persistence in lesions of patients with mild primary infection did not seem to differ from that in patients with recurrent infection.     

Vaccination for herpes simplex genitalis.

Type-specific vaccines containing heat-inactivated herpes simplex hominis virus type 1 or 2 have been developed for the treatment of herpes simplex genitalis. When patients with recurrent herpes genitalis were treated with the type 2 vaccine the clinical course of the disease improved and the eruption-free interval was extended. In severe cases, especially in permanent genital herpes, the concurrent administration of vaccine and immunoglobulin concentrates improved the clinical course of the disease. Antibody titres and the in-vitro stimulation of lymphocytes with phytohaemagglutinin or herpes simplex hominis virus antigens remained constant during administration of the vaccine.     

Vaccination for herpes simplex genitalis.

Type-specific vaccines containing heat-inactivated herpes simplex hominis virus type 1 or 2 have been developed for the treatment of herpes simplex genitalis. When patients with recurrent herpes genitalis were treated with the type 2 vaccine the clinical course of the disease improved and the eruption-free interval was extended. In severe cases, especially in permanent genital herpes, the concurrent administration of vaccine and immunoglobulin concentrates improved the clinical course of the disease. Antibody titres and the in-vitro stimulation of lymphocytes with phytohaemagglutinin or herpes simplex hominis virus antigens remained constant during administration of the vaccine.     

Epidemiology of recurrent genital herpes simplex virus types 1 and 2

OBJECTIVES: To describe the epidemiology of type specific recurrent genital herpes, and to compare the duration of recurrent genital lesions caused by herpes simplex virus (HSV) types 1 and 2. METHODS: Participants were enrolled at clinics across the United States. Adults suspected of having active genital herpes were eligible. Lesions were cultured for HSV and typed. Data from 940 participants with recurrent culture positive HSV lesions were analysed. Pearson's chi(2) and Fisher's exact tests, multivariate logistic regression models, and a stratified Cox proportional hazards model were used to compare epidemiological characteristics and lesion duration of HSV-1 and HSV-2. RESULTS: HSV-1 was present in 4.2% of the recurrent HSV culture positive lesions. HSV-1 was most prevalent among whites (6.5%) and individuals with 0-2 recurrences in the previous year (9.1%) and, among men, in those with rectal/perirectal lesions (13.2%). Longer lesion duration was not significantly associated with virus type (hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.65 to 1.38, p = 0.79), but was associated with male sex (HR 0.85, 95% CI 0.74 to 0.99, p = 0.04), and HIV seropositivity (HR 0.62, 95% CI 0.48 to 0.81, p<0.01). CONCLUSIONS: The authors found that, in the United States, recurrent genital HSV-1 is relatively rare in the STD and HIV clinic setting, especially among black people. Among men, rectal/perirectal recurrent lesions are more likely to be caused by HSV-1 than are penile lesions. In addition, lesion duration depends on sex and HIV status but not virus type. These findings shed new light on the type specific epidemiology of recurrent genital HSV, and suggest that type specific testing can inform the prognosis and management of genital herpes.     

Incidence of serum antibody titers against herpes simplex virus in Japanese patients

Herpes simplex virus (HSV) establishes latency in the sensory neuronal ganglia after primary infection, and occasionally causes recurrent infection, mainly on the lips or genitalia. Previous reports revealed an age‐related increase in HSV‐immunoglobulin G seropositive subjects in a hospital‐based study and the general population in Japan. In this report, we retrospectively analyzed the results of serological tests against HSV, in which subjects were diagnosed with or suspected as having HSV infection. A total of 1216 subjects with at least one complement fixation (CF) result were included. Of these, 771 subjects (63.4%) were positive at first visit. When stratified by age, incidence of positive patients linearly increased with age from teenagers (44.9%) to those in their 80s (88.9%). Positivity in women was higher than in men overall; significantly higher incidence was observed in women aged in their 30s, 40s and 60s. When observing changing HSV‐CF titers over time in 81 initially negative patients, 18 (22%) seroconverted during the 2121‐day observation period. In this study, we clearly show that distribution of HSV‐CF titers is similar to previous HSV‐immunoglobulin G results. This correlation is probably caused by the continual subclinical proliferation of HSV, thus maintaining CF titers. Our observations provide current data on the incidence of HSV, reconfirming that serological examination is unreliable in diagnosing recurrent herpes, and the majority of infected subjects are asymptomatic.     

A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2

OBJECTIVES: To explore epidemiological evidence about the interaction of herpes simplex virus (HSV) 1 and HSV-2 infections. METHODS: A systematic review was undertaken of published epidemiological studies describing the pattern of HSV-1 or HSV-2 by age, and the coincidence of the two viral infections. RESULTS: In cross sectional studies the unadjusted odds of HSV-2 are greater in those with HSV-1 infection in study populations categorised as "low risk" (p = 0.06) and across European populations (p = 0.001). This was not evident in "high risk" populations or in the United States. This increased risk of HSV-2 in those with HSV-1 infection does not agree with the results of prospective studies where there is a non-significant trend towards a lower risk of HSV-2 infection associated with previous HSV-1 infection. CONCLUSIONS: "Low risk" and European populations have a relatively low HSV-2 seroprevalence and infection is more concentrated in those with characteristics putting them at high risk for both HSV-1 and HSV-2. This confounding could mask any protective effect of HSV-1, which is hinted at, but not demonstrated, in prospective and adjusted studies.     

Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a nationwide population based survey

BACKGROUND: Studies demonstrating previous herpes simplex virus (HSV) type 2 infection as a risk factor for HIV transmission, and the development of a HSV vaccine candidate, have emphasised the need for worldwide population based studies of HSV seroprevalence. The only nationwide seroprevalence studies have been conducted in the United States. METHODS: An Australia-wide, population based study of HSV-1 and HSV-2 seroprevalence was conducted, using serum and sociodemographic data collected between 1999-2000, for a representative study of risk factors for diabetes in over 11 000 adults. A stratified random sample of 4000 was tested for HSV-2 and 1000 for HSV-1, with sampling and weighting for various demographic factors. RESULTS: Seroprevalence of HSV-2 in Australian adults was 12%. Prevalence in women (16%) was twice that in men (8%). Rural populations had a lower prevalence (9%) than metropolitan (13%), and Indigenous had a higher prevalence (18%) than the non-Indigenous populations (12%). The seroprevalence of HSV-1 was 76% with significant differences by age group, sex and Indigenous status. CONCLUSION: These are the first nationwide data to compare with US studies. HSV-2 infection is less common in Australia than the United States, and this will allow planning for combating HIV transmission in high prevalence populations in northern Australia. In addition, the high HSV-1 seroprevalence will be important for future deployment of genital herpes vaccines.     

Pathogenic microbial flora of genital ulcers in Sheffield with particular reference to herpes simplex virus and Haemophilus ducreyi.

The pathogenic microbial flora of genital ulcers in 161 (80 men and 81 women) unselected patients was studied prospectively. In only one case was Treponema pallidum responsible whereas herpes simplex virus was considered to be the cause of 130 (80.8%) genital ulcers. H ducreyi was isolated from 46 (28.6%) patients, most commonly as a secondary pathogen in herpetic lesions. Two or more pathogens were isolated from the ulcers in 67 (41.6%) patients, and in 21 (13%) patients no pathogens were isolated. Our results indicate an urgent need for antiviral treatment to reduce the local reservoir of genital herpes, challenge traditional concepts about the prevalence of H ducreyi in Britain, and call for a reappraisal of its role in the causation of genital ulcers.     

Incidence and prevalence of herpes simplex virus infections in adolescent women

OBJECTIVES: We conducted this study to examine the incidence, prevalence, and risk factors for herpes simplex virus (HSV) 1 and HSV 2 infection in a cohort of young women who were closely followed for acquisition of sexually transmitted infections. STUDY DESIGN: Women between the ages of 14 and 18 years had blood and genital specimens obtained quarterly to test for incident sexually transmitted infections. Subjects also had 2 12-week periods each year when they kept a detailed behavioral diary and performed weekly vaginal swabs. Serum specimens were tested for HSV 1 and HSV 2 antibody, and genital specimens were tested for HSV DNA by PCR. RESULTS: A total of 100 subjects enrolled and had at least 2 sera that could be analyzed for seroconversion. The mean age of the subjects was 15.8 years at entry. The HSV 1 and HSV 2 seroprevalence at entry was 59.6% and 13.5%, respectively. During the study, 4 subjects acquired HSV 1 antibody and 7 acquired HSV 2 antibody, but there were no cases of symptomatic HSV infection identified. The annualized incidence among susceptible individuals was 8.9% for HSV 1 and 7.4% for HSV 2. Three of the 7 HSV 2 sero-converters had HSV 2 DNA detected in vaginal swabs. Age, duration of sexual activity, and the presence of other sexually transmitted infections were predictors of HSV 2 antibody positivity. CONCLUSIONS: Acquisition of HSV 1 and HSV 2 is relatively common in adolescent women, although symptomatic infection is uncommon. HSV 2 is shed in the genital tract despite the lack of symptoms.     

Immune responses to herpes simplex virus in patients with facial herpes simplex and those with eczema herpeticum

The immune response to herpes simplex virus (HSV) was studied in 59 patients with primary and recrudescent facial HSV infections. The patients included nine with atopic eczema, seven of whom had eczema herpeticum (EH). All patients had antibodies to HSV (measured by ELISA) and all but three had HSV-specific cell mediated immunity (CMI) (measured by in vitro lymphoproliferation). Thirteen control subjects were negative for both tests. All three patients with absent CMI to HSV had suffered from severe EH and had depressed CMI to HSV for several months following an attack. In two of these EH patients, a positive CMI response was produced by in vitro removal of CD8 + ve T lymphocytes from peripheral blood mononuclear cells using a panning technique. Thus the absence of CMI to HSV in these patients was due to suppressor cell function rather than a lack of specifically responsive cells. The other four EH patients with normal CMI to HSV had suffered less severe EH, but no association between the absence of CMI to HSV and serum IgE level or activity of the eczema was apparent in the atopic patients. No specific anti-HSV IgE antibody was detectable.     

The epidemiology of genital infection with herpes simplex virus types 1 and 2 in genitourinary medicine attendees in inner London

OBJECTIVE: To characterise the epidemiological and clinical features of genital herpes and the diagnostic role of HSV-2 specific serology in an ethnically diverse cohort of genitourinary medicine (GUM) attendees in inner London. METHODS: Genital swabs (n = 186) were tested by real time polymerase chain reaction (PCR) and serum samples (n = 70) by HSV-2 specific enzyme linked immunoassay (ELISA). RESULTS: Among 186 patients (median age 29 years), 104/186 (56%) were male and 176/186 (95%) heterosexual; ethnicity was predominantly black Caribbean (76/186, 41%), white (65/186, 35%), or black-African (41/186, 22%). The most common lesion sites were penis (85/104 men, 82%) and vulva (63/82 women, 77%); 114/186 (61%) patients were diagnosed clinically with first episode disease. Women were more likely to present <5 days of onset (p = 0.008). Black Caribbean patients were more likely to present > or = 5 days (p = 0.04) and decline HIV testing (p = 0.03). By PCR, 108/186 (58%) swabs tested positive for HSV-1 (7/108, 6.5%) or HSV-2 (101/108, 93.5%). Independent predictors of a positive PCR were heterosexual group, <5 days of onset, and visible genital ulceration on examination. HSV-2 was associated with black Caribbean and black African ethnicity; HSV-1 with white ethnicity (p = 0.006). By HSV-2 specific serology, 16/42 (38%) first episodes caused by HSV-2 were recurrent infections, and 7/19 (37%) patients with recurrent genital disease but negative PCR had genital herpes. CONCLUSIONS: Epidemiological trends in genital HSV-1 and HSV-2 infection appear to vary between ethnic groups in the United Kingdom. HSV-2 specific serology improves diagnostic accuracy in GUM populations where most genital infections are caused by HSV-2.     

HSV-2与HIV-1感染相关性研究进展

HSV-2与HIV-1的感染有协同作用,HSV-2感染可增加HIV-1的感染率,并可能提高HIV-1的传播率.生物学实验证据表明,HSV-2合并感染可以促进HIV-1的增殖,流行病学数据也表明HSV-2感染与HIV-1感染的相关性.概述两者相关性的流行病学证据和生物学作用机制,为将HSV-2作为HIV-1感染的危险因素以及通过行为干预、抗病毒治疗HSV-2来防控HIV-1的传播提供理论依据.

Abstract：

Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1)are synergistic copathogens. Biological and epidemiological evidence suggests that HSV-2 infection increases the risk of HIV-1 acquisition and may facilitate the transmission of HIV-1. This review focuses on the epidemiological relationship and biological interaction between HSV-2 and HIV-1. Based on these data, HSV-2infection should be targeted as a risk factor for HIV-1 acquisition, and more prevention through behavioural interventions and antiviral suppression should be incorporated into the strategy for HIV-1 prevention.     

Seroprevalence and seroincidence of herpes simplex virus type 1 and herpes simplex virus type 2 infections in a cohort of adolescents in Italy

OBJECTIVE: The objective of this study was to improve the knowledge on the epidemiology of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in Italy. GOAL: The goal of this study was to study the seroincidence and seroprevalence of HSV-1 and HSV-2 infections among Italian adolescents. STUDY: We conducted a retrospective longitudinal study among 345 Italian adolescents tested for anti-HSV-1 and anti-HSV-2 on samples collected at 11 and 17 years of age. RESULTS: At 11 years of age, the HSV-1 prevalence was 51.6% and the HSV-2 prevalence was 2.6%; when 17 years old, these rates increased to 61.4% and 4.9%, respectively. The HSV-1 incidence was 1.6 per 100 person-years and was higher among females. The HSV-2 incidence was 0.4 per 100 person-years with no gender differences. CONCLUSION: HSV-1 is apparently widespread among Italian adolescents, whereas HSV-2 is limited. These data are of paramount importance when considering that HSV-1 can cause genital herpes and that HSV-2 plays a role in HIV transmission.