Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students

A retrospective review of genital herpes simplex virus (HSV) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993. BACKGROUND: Herpes simplex virus (HSV) type 1 is usually thought to cause less than 30% of genital herpes infections in the United States, but the proportion of infections resulting from HSV-1 is increasing in some populations. GOAL: The goal was to review the relative proportion of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of U.S. college students and to assess trends in the change of this proportion over time. STUDY DESIGN: Genital HSV isolates collected at a university student health service from 1993 to 2001 (n = 499) were reviewed retrospectively. Analyses included comparisons of isolates by HSV type, age group, and sex. RESULTS: The proportion of newly diagnosed genital herpes infections resulting from HSV-1 increased from 31% in 1993 to 78% in 2001 (P <0.001, linear trend P <0.001). HSV-1 was more common in females than males, but increases were noted for both sexes. HSV-1 was more common in persons aged 16 to 21 than in persons aged 22 or older. CONCLUSIONS: HSV-1 has become the most common cause of newly diagnosed genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio.     

Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey

BACKGROUND: Herpes simplex virus (HSV) infections are among the most common infectious diseases in humans. The prevalence of herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) varies widely across the world. HSV-2 infection is the primary cause of genital herpes. It is highly prevalent in human populations in many parts of the world, and is the most common cause of genital ulcer disease worldwide. In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few data have been published regarding the seroprevalence of herpes simplex infection, while no data exist regarding the Turkish population. METHODS: We aimed to investigate the prevalence of HSV-1 and HSV-2 in selected populations in Turkey. A cross-sectional study was conducted involving 2082 serum samples of 725 adults, 300 pregnant women, 200 blood donors, 483 sex workers and 110 patients with genital warts and 264 hotel staff in Istanbul, Turkey. All serum samples were assessed for HSV1 and HSV-2 IgG antibodies using an HSV-type specific, enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of HSV-2 and HSV-1 antibodies was 4.8 and 85.3% in sexually active adults; 5.5 and 96% in blood donors; 5 and 98% in pregnant women, 17.3 and 93.6% in patients with genital warts; 8.3 and 97.3% in hotel staff; and 60% and 99% in sex workers. CONCLUSION: These results confirm a higher prevalence of HSV infection than estimated, especially in high risk groups in Turkey. The high prevalence of HSV infection underlines the need for education among these populations.     

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.     

Confirmation of herpes simplex virus type 2 infections in herpes-like genital lesions by a simple complement-fixation test

The presence of complement-fixing antibody to an early herpes simplex virus type 2 (HSV-2) antigen (the AG-4 antigen) was correlated with HSV-2 infection in the sera of patients with genital herpes. Eighty-eight per cent of sera taken two weeks after clinical diagnosis of a primary or recurrent herpes infection in patients, confirmed to have HSV-2 by virus isolation and typing, contained the anti-AG-4 complement-fixing antibody. None of the patients with genital HSV-1 had the antibody, and only 9% of controls or patients with facial HSV-1 infection had positive results for the antibody. This correlation was used to identify genital HSV-2 infections when either no virus sample had been taken or when virus isolations had been unsuccessful. Thus, a simple complement-fixation test can confirm an HSV-2 virus infection without isolation of the virus from the herpetic lesion.     

Confirmation of herpes simplex virus type 2 infections in herpes-like genital lesions by a simple complement-fixation test.

The presence of complement-fixing antibody to an early herpes simplex virus type 2 (HSV-2) antigen (the AG-4 antigen) was correlated with HSV-2 infection in the sera of patients with genital herpes. Eighty-eight per cent of sera taken two weeks after clinical diagnosis of a primary or recurrent herpes infection in patients, confirmed to have HSV-2 by virus isolation and typing, contained the anti-AG-4 complement-fixing antibody. None of the patients with genital HSV-1 had the antibody, and only 9% of controls or patients with facial HSV-1 infection had positive results for the antibody. This correlation was used to identify genital HSV-2 infections when either no virus sample had been taken or when virus isolations had been unsuccessful. Thus, a simple complement-fixation test can confirm an HSV-2 virus infection without isolation of the virus from the herpetic lesion.     

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.     

Epidemiology of genital herpes simplex virus infections in a community-based sample in France: results of the HERPIMAX study

OBJECTIVE: The objective of this study was to provide information on the prevalence of herpes simplex infections in the general population in Europe. GOALS: The goals of this study were to determine the prevalence of clinically probable genital herpes and the relationship between serotype and clinical expression in a French community-based sample. STUDY: A total of 4410 subjects chosen at random were serotyped for herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Data on symptoms were obtained by questionnaire allowing retrospective diagnosis of clinically probable genital herpes. RESULTS: Questionnaire data and serotype were available for 3192 subjects. Seroprevalences of HSV-1 and HSV-2 were 65.6% and 15.5%, respectively. Prevalence of clinically probable genital herpes was 11.8%, identified in 11.1% of HSV-1-positive subjects and 26.8% of HSV-2-positive subjects, with a lower prevalence in those coinfected with both virus types. CONCLUSIONS: Clinically probable genital herpes was observed in one fourth of subjects with HSV-2 infections and in some subjects with HSV-1 infection. Coinfection with HSV-1 appeared to protect against symptom expression in subjects infected with HSV-2.     

Update on antiviral therapy for herpes simplex virus infection

ABSTRACT: The prevalence of infection with herpes simplex virus (HSV) continues to increase largely due to the inability of current antiviral agents to eradicate latent infection. This article reviews strategies to slow the transmission of HSV infection, most importantly through the development of vaccines, as well as established and emerging choices for treatment of primary and recurrent genital herpes, herpes labialis, infections in immunocompromised hosts, and acyclovir-resistant infections. The role of chronic suppressive therapy in the management of genital herpes as well as its potential impact on transmission rates will also be discussed.
Herpes simplex virus (HSV) is a widespread pathogen in the United States, with more than 100 million U.S. citizens having serologic evidence of HSV-1 infection and 40–60 million, nearly one-fifth of the adolescent and adult population, infected with HSV-2 (1,2) . The prevalence of HSV-2, the major cause of genital herpes, has increased 30% since the late 1970s (2) . The fact that most of those infected with HSV are asymptomatic and yet may still be subclinically shedding virus further complicates efforts to slow the spread of transmission (3) . Therefore proper management of herpetic infections requires that the clinician be able to effectively diagnose those with HSV infection, to educate them regarding means of spread and symptoms indicative of infection, and to adequately treat infections which are identified in order to alleviate patient symptoms and slow the transmission of the virus. We review options for preventing infection, treating primary infections, and treating recurrent infections in order to accomplish these goals.     

First episodes of genital herpes in a Swedish STD population: a study of epidemiology and transmission by the use of herpes simplex virus (HSV) typing and specific serology

OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners. METHODS: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes. CONCLUSIONS: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.     

Trends in herpes simplex virus type 1 and 2 infections among patients diagnosed with genital herpes in a Finnish sexually transmitted disease clinic, 1994-2002

OBJECTIVE: The objective of this study was to analyze the proportion of herpes simplex virus types 1 and 2 (HSV-1 and -2) in genital infections during a 9-year period (1994-2002) in a Finnish sexually transmitted disease (STD) clinic population. STUDY DESIGN: We analyzed prospectively the proportion of HSV-1- or -2-positive culture samples from our STD clinic patients with genital herpes during years 1994-2002 and compared the proportions of HSV-1 and HSV-2 findings with the age and gender of the patients. RESULTS: The proportion of HSV-1 infections increased from 18.7% (39 of 209) in 1994-1996 to 25.9% (52 of 201) in 2000-2002 (P = 0.032). Female patients with genital herpes and laboratory isolation of HSV-1 were 35.9% of the cohort from 1994-1996 and 67.3% of the cohort from 2000-2002. The mean age of male patients with HSV-1 decreased from 29.3 years in 1994-1996 to 24.1 years in 2000-2002 (P = 0.023). CONCLUSIONS: An increase in the proportion of genital infections caused by HSV-1 was found. The increase was mainly the result of the increase in the number of female patients with HSV-1. Male patients acquire genital HSV-1 infection at a younger age than 10 years ago.     

Premarket evaluation of the POCkit HSV-2 type-specific serologic test in culture-documented cases of genital herpes simplex virus type 2 [see comment

BACKGROUND AND OBJECTIVES: The genital herpes epidemic continues, in part, because patients with subclinical or atypical presentations cannot be identified by most herpes simplex virus (HSV) antibody tests. A new product, POCkit HSV-2, has been developed to rapidly and accurately detect antibodies to HSV type 2 (HSV-2) in capillary blood or serum. GOAL: Sera from patients with culture-documented genital or oral herpes were tested to determine the sensitivity and specificity of the POCkit HSV-2 rapid point-of-care antibody test (Diagnology, Belfast, Northern Ireland). STUDY DESIGN: Sera from 50 patients with culture-documented HSV type 1 (9 oral, 41 genital) and from 253 patients with genital HSV-2 were tested by POCkit HSV-2 for HSV-2 antibodies. Each subject had a positive culture for HSV within 6 months of serum collection. Sera were preselected to include only those that were seropositive to the respective virus subtype by University of Washington Western blot. RESULTS: Compared with viral culture and Western blot analysis, sensitivity of the POCkit HSV-2 test for HSV-2 antibody was 96%; specificity was 98%. CONCLUSION: This test provides rapid, accurate identification of HSV-2 antibody in subjects with established HSV infections.     

Natural history of genital herpes simplex virus type 1 infection

BACKGROUND: Herpes simplex virus type 1 (HSV-1) has been increasingly reported as a cause of genital herpes, yet there have been few studies on the long-term natural history of this infection.GOAL The goal was to examine the clinical course of genital HSV-1 infection. STUDY DESIGN: This was a cohort study of patients presenting with culture-proven primary genital HSV-1 infection. RESULTS: The median follow-up of the 77 patients was 736 days. The overall rate of recurrences was 1.3/year in the first year of infection, decreasing to 0.7/year in the second year. In the first year of infection, 43% of study patients did not have a recurrence. In the second year of infection, 67% of study patients did not have a recurrence. CONCLUSION: Genital HSV-1 recurs infrequently in most patients, and the rate decreases further in the subsequent years of infection. Because the prognoses of genital HSV-1 and HSV-2 infections differ, determination of the viral type is important for patient counseling.     

Lack of evidence for intertypic recombinants in the pathogenesis of recurrent genital infections with herpes simplex virus type 1

Clinical observations indicate that herpes simplex virus type 1 (HSV-1) is significantly less likely than herpes simplex virus type 2 (HSV-2) to establish latency in (or reactivate from) sacral ganglionic tissue. In an effort to identify viral functions associated with latency, we analyzed HSV-1 isolates from three patients with established recurrent genital herpes and sought evidence of DNA sequences and proteins similar to those found in HSV-2. By restriction endonuclease cleavage patterns and by DNA hybridization analysis using either whole HSV-2 DNA or several cloned segments of HSV-2 DNA as probes, we found that the three HSV-1 isolates from patients with recurrent genital herpes showed no unusual homology to HSV-2 as compared with other HSV-1 isolates. Similarly, the proteins of these isolates could not be distinguished from those of other HSV-1 isolates and were distinct from those of HSV-2. At this level of resolution, there was no evidence to suggest that these recurrent genital HSV-1 isolates were intertypic recombinants, nor did they show any other unusual similarity to HSV-2.     

Acceptance and outcome of herpes simplex virus type 2 antibody testing in patients attending an STD clinic--recognized and unrecognized infections

The majority of herpes simplex virus type 2 (HSV-2) genital infections are asymptomatic. We wanted to evaluate the acceptance of HSV-2 antibody testing among people attending an STD clinic and to estimate, after counselling, the percentage of recognized and unrecognized HSV-2 infections. First visitors to an STD clinic were invited to participate by answering a questionnaire and taking a blood test for HSV-2 antibodies. HSV-2 seropositive individuals, who were unaware of having genital herpes, were offered an HSV-2 counselling visit and follow-up. Of 1769 patients offered testing, 57% accepted. Of 152 (15%) HSV-2 seropositive individuals, 41% had a self-reported history of genital herpes, approximately 30% had genital symptoms and 30% had no genital symptoms. The percentage of patients reporting genital symptoms was much higher in HSV-2 seropositives (45%) without a history of genital herpes than in an HSV-2 seronegative group (28%). HSV-2 antibody testing should be performed generously in all cases of uncharacteristic genital symptoms.     

Development and use of a type-specific antibody avidity test based on herpes simplex virus type 2 glycoprotein G

OBJECTIVES: It is difficult to discriminate between lesions resulting from recently acquired versus established genital herpes simplex virus type 2 (HSV-2) infection. Methods not based on history or serum IgM status are needed. GOAL: Our goal was to use type-specific gG-2 antibody avidity determinations based on HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA) to identify new infections. STUDY: Sera (N = 168) from 71 patients with first-episode genital herpes and 45 sera from 21 patients with recurrent episodes were tested. RESULTS: Median avidity increased from 30.2 in sera drawn 6 weeks after infection (P <0.001). Patients with recurrent episodes and established HSV-2 infections (median, 6.1 years' duration) had higher avidity antibodies (median, 92.7; range, 55.1-100) than patients after first episodes (median, 33.7; range, 6.4-73.9; P <0.001). CONCLUSION: Avidity testing based on HerpeSelect ELISA could be a cost-effective method to identify patients with new HSV-2 infections.     

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.     

Apolipoprotein E-epsilon 4 and recurrent genital herpes in individuals co-infected with herpes simplex virus type 2 and HIV

Apolipoprotein E (APOE) alleles have been associated with the severity of, or susceptibility to, infection by various microbes. We investigated the potential association between the APOE-epsilon 4 allele and the rate of recurrence of genital herpes in patients who were HIV positive and herpes simplex virus type 2 (HSV-2) seropositive. The APOE-epsilon 4 allele was significantly associated with recurrent genital ulceration independent of ethnicity, antiretroviral therapy and CD4 count (OR 8.3; 95% CI 2.4 to 28.5). To our knowledge, this is the first published study to demonstrate this association and suggests that APOE-epsilon 4 may represent a future prognostic marker for symptomatic recurrence of genital herpes in individuals with HIV.     

Herpes simplex virus type 1 remains the principal cause of initial anogenital herpes in Edinburgh, Scotland

GOAL: The goal of this study was to investigate the trends in the prevalence of anogenital herpes caused by herpes simplex virus (HSV) type-1 and HSV-2 among patients attending a sexually transmitted infections clinic. METHODS: We conducted a retrospective study of virologically proven first-episode genital herpes diagnosed in the Department of Genitourinary Medicine in Edinburgh between 1989 and 2002. RESULTS: First-episode anogenital herpes was associated with HSV-1 in 659 (62%) women and 294 (42%) men (P <0.0002). HSV-1 was recovered more often from women younger than 25 years than from older women (P <0.0005). For both HSV-1 and HSV-2 infections, the median ages of heterosexual men (26.0 and 28.0 years, respectively) were significantly higher than those of women (23.0 and 25.0 years, respectively)(P <0.05). The median age of men who have sex with men with HSV-1 (29.0 years) was significantly higher than that of heterosexual men (26.0 years)(P <0.01). CONCLUSION: HSV-1 remains the most common cause of symptomatic first-episode anogenital herpes, especially among young women in our clinic population.     

Herpes simplex virus type 1 is the prevailing cause of genital herpes in the Tel Aviv area, Israel

BACKGROUND AND GOAL: The changing epidemiology of genital herpes with the increasing importance of herpes simplex virus (HSV) type 1 prompted a study on the relative prevalence of HSV-1 and HSV-2 among cases of genital herpes in the Tel Aviv area, Israel. STUDY DESIGN: A retrospective laboratory-based study of positive genital and nongenital herpes cultures performed at the Beilinson Medical Center between 1993 and 2002. Data regarding the number of isolates of each type and the age and sex of patients with genital lesions were retrieved from the database. Cultures were performed using Vero cells, and positive results were confirmed and typed by immunofluorescence. RESULTS: A total of 285 positive genital cultures and 659 positive nongenital cultures were recorded. HSV-1 was identified in 189 (66.3%) of the positive genital specimens and in 656 (99.55%) of the nongenital specimens. HSV-1 was isolated in 174 of 262 (66.4%) female subjects and 15 of 23 (65.2%) male subjects. The proportion of HSV-1 genital isolates was 72.7% in patients 15 to 24 years of age, 62% in those 25 to 44 years, and 46% in those aged 45 years or older. Overall, the annual isolation rate of genital HSV-1 has not changed markedly over the years. CONCLUSION: Herpes simplex virus type 1 has clearly been the predominant HSV type isolated from genital specimens in the Tel Aviv area over the last decade.     

Seroprevalence and correlates of herpes simplex virus type 2 among urban Tanzanian women

BACKGROUND: Data on herpes simplex virus type 2 (HSV-2) among women in the general population of developing countries are limited. GOALS: The goal of the study was to determine the seroprevalence of HSV-2 and to identify clinical, demographic, and behavioral correlates among women attending primary health care clinics. STUDY DESIGN: This was a cross-sectional survey of 382 randomly chosen women aged 15 to 49 years. RESULTS: The seroprevalence of HSV-2 was 39%. Only 2% had a history of genital herpes. HSV-2 was associated with antibody to HIV-1 (OR=2.3 [CI, 1.1-4.7]), syphilis (OR=4.7 [CI, 1.4-4.7]), and genital ulcers (OR=9.7 [CI 2.5-36.9]). Age, sexual debut, number of sex partners, and history of spontaneous abortion were found to be significantly associated with HSV-2. Eighty-two percent of the women with genital ulcers were HSV-2-seropositive, while syphilis accounted for 6% of cases. HSV-2 may thus be the most common cause of genital ulcers in this population. CONCLUSION: In view of the high HSV-2 seroprevalence and its association with HIV-1 and genital ulcers, integration of HSV-2 therapeutic management in STD syndromic algorithms is recommended. Counseling on symptom recognition, asymptomatic shedding, and preventive measures is needed.