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.     

Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions

BACKGROUND: A sensitive and specific method for detecting herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for diagnosing genital and cutaneous infections. GOAL: The goal of this study was to compare quantitative real-time polymerase chain reaction (qPCR) with virus culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed. Duplicate swabs for PCR and virus culture were collected from 89 patients attending our sexually transmitted infection and dermatology clinic. RESULTS: The duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens and virus was isolated in 45 (50%) cases. First-episode infections showed higher viral quantities with a median value of 4.2 x 10 copies per reaction compared with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be the cause of first-episode genital infections (72%), and HSV-2 of recurrent and atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive method for diagnosing genital herpes, and the duplex format is convenient for typing. The method increased the detection rate by 27% compared with virus culture.     

单纯疱疹病毒1型致原发性生殖器疱疹一例

患者女,23岁。因外阴红肿、刺痛4 d入院。4 d前出现会阴瘙痒、分泌物增多,查念珠菌阳性,拟诊念珠菌性阴道炎,给予氟康唑胶囊150 mg顿服,复方明矾散、双唑泰栓及联苯苄唑乳膏外用,3 d前瘙痒加重,出现轻微疼痛,予聚维酮碘溶液阴道冲洗,制霉菌素阴道泡腾片及硝酸咪康唑栓治疗,症状无改善,2 d前外阴明显肿胀,大量水疱及脓疱,渗出,行走时疼痛明显,外院拟急性女阴溃疡给予头孢曲松、泼尼松治疗,效果不佳,疼痛加剧,呈反复持续发作的刺痛,加用盐酸曲马多注射液肌内注射,疼痛未能改善……     

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.     

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.     

Laboratory diagnosis of herpes simplex virus type 1 and type 2 infections

Herpes simplex virus (HSV) is known to infect several body sites. Most commonly HSV infection results in lesions around the mouth or in the genital area. Infection at these sites may also be subclinical. Over the past decade HSV has been increasingly recognized as an important cause of both mild and severe diseases in a wide range of patients. Two distinct types of HSV are known, HSV-1 and HSV-2, and many antigens are shared between the two. Infection with either type of virus can occur early in life, although infection with HSV-2 becomes common only after puberty. The most common manifestation of HSV-1 infection is the orofacial “fever blister,” while HSV-2 is most often responsible for genital lesions.^1,2 Either virus type can, however, cause disease in almost any site of the body and can recur frequently. This recurrence of disease from an inapparent or latent state makes HSV infection unique among the common viral infections.Mistakes in diagnosis of HSV infections based on clinical findings alone are not uncommon. Herpetic lesions have been confused with allergic reactions, drug reactions, and lesions due to other infectious agents. Besides the medical importance of HSV in special situations, the social impact of having “herpes” is of considerable concern is almost everyone. Therefore, precise diagnosis of HSV infection is of paramount importance, particularly since effective antiviral therapy is available for many forms of the disease.Morphologically, all herpesviruses are alike (Fig. 1); therefore, it is not possible to differentiate members of the group by their structure alone. Although rapid techniques for diagnosis of HSV infection are constantly being refined and improved, virus isolation in tissue culture is still the most definitive method of detecting HSV, and it is the most widely used. In this chapter detailed procedures for HSV isolation and typing are described, with brief reviews on methods that have been used in conjunction with virus isolation when cell culture facilities are not available.     

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.     

Acquisition of concomitant oral and genital infection with herpes simplex virus type 2

Primary oral and genital infections caused by herpes simplex virus type 2 were diagnosed in an 18-year-old female. A history of sexual practices was critical in determining the anatomic sites of infection. Restriction endonuclease analysis of viral DNAs helped to identify the male sexual partner from whom the virus had been acquired. He had been infected recently by a previous sexual partner but had not yet developed lesions. Clinicians should obtain a history of sexual practices from patients with newly acquired genital herpes and should advise patients with genital herpes that transmission of virus to sexual partners can occur in the absence of overt lesions.     

Serological evaluation of herpes simplex virus type 1 and type 2 infections in pregnancy

OBJECTIVE: Serological evaluation of herpes simplex virus infections during pregnancy. METHODS: 2991 serum samples were obtained during 1st, 2nd, and 3rd trimester from 997 pregnant women. Baculovirus expressed glycoproteins gG1 (HSV-1) and gG2 (HSV-2) were used as antigens in ELISA for HSV-1 and HSV-2 IgG and IgA antibodies. RESULTS: The prevalence of HSV-1 gG1 antibodies was 70% and that of HSV-2 gG2 antibodies 16%. Among susceptible women we found five (0.6%) cases with serological evidence of primary HSV-2 infection during pregnancy. Evidence of active HSV-1 infection was found in nine (0.9%) cases. Decline of HSV-2 gG2 IgG antibody levels during pregnancy was pronounced compared with HSV-1 gG1 IgG antibody levels (p < 0.01); also the proportion of seroreversions was considerably higher among HSV-2 seropositives (25%) than among HSV-1 seropositives (3%) (p < 0.001). CONCLUSIONS: HSV-2 gG2 IgG antibodies were readily distinguished from HSV-1 gG1 IgG antibodies by the glycoprotein gG ELISAs. Serological assays for gG2 antibodies should guard against the decline of specific antibodies during pregnancy.     

Predictors of herpes simplex virus type 2 antibody positivity among persons with no history of genital herpes

BACKGROUND: The demographic, historical, and behavioral factors that predict a positive herpes simplex virus type 2 (HSV-2) antibody test in persons without a history of genital herpes have not been well-defined. METHODS: Individuals (age 14-30 years) without a history of genital herpes completed a questionnaire and were offered free HSV-2 antibody testing. Factors from the questionnaire were correlated with the HSV-2 antibody result. RESULTS: Univariate analysis showed that female gender was significantly associated with positive test results. In gender-specific, multiple logistic regression models, a positive HSV-2 antibody test among men was associated with older age, non-white race, and a history of sexually transmitted disease (STD). Gender-specific symptom scores from the questionnaire were not predictive in either gender, but the gender-common symptom score was marginally predictive of a positive HSV-2 antibody test in women. Among women, older age, non-white race, and STD history predicted a positive test. CONCLUSIONS: Among young persons with no history of genital herpes who agreed to HSV-2 antibody testing, increasing age, non-white race, and a history of an STD were predictors of a positive test. A history of frequent pain, itching, burning, and rashes in the anogenital region was marginally associated with positive HSV-2 tests in women. These results might help guide selective use of HSV-2 antibody screening.     

间接免疫荧光法检测生殖器疱疹病毒

目的:评价间接免疫荧光试验(IFA)在生殖器疱疹(GH)诊断中的应用价值。方法:采用以单纯疱疹病毒(HSV)型共同性单克隆抗体为夹心的IFA法,检测了120例临床诊断为GH患者皮疹中的HSV,并与病毒培养法进行比较。结果:IFA检测HSV的总阳性率为85.8%,高于病毒培养法的阳性率(70.8%,χ2=12.04,P<0.01)。两种方法检测GH水疱内的HSV阳性率分别为93.3%和90.0%,无明显差异(χ2=1.96,P>0.05);而检测糜烂和结痂性皮疹内的HSV时,IFA的阳性率分别为92.6%和69.4%,均分别高于病毒培养法(75.9%,χ2=5.82,P<0.05;47.2%,χ2=14.17,P<0.01)。结论:IFA法具有简单、快速、敏感性高的优点,适于检测GH患者皮疹内HSV,有临床实用价值。     

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.     

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.     

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.     

The psychosocial impact of testing individuals with no history of genital herpes for herpes simplex virus type 2

BACKGROUND: Although approximately 20% of the population has a genital herpes (HSV-2) infection, 80% of these infections are unrecognized or asymptomatic. Serologic identification of HSV-2 leads to recognition of infection, which could lead to behavioral changes that reduce transmission. However, there has been concern that HSV-2 testing among persons without symptoms will cause substantial psychosocial harm. GOAL: The goal of this study was to assess the psychosocial impact of an HSV-2 diagnosis among individuals without a history of genital herpes attending a sexually transmitted disease (STD) clinic. STUDY: We conducted a cohort study of persons with no history of genital herpes attending an STD clinic and seeking herpes testing. Two follow-up interviews were conducted 1 week and 3 months after persons received their test results. Serum was tested using HerpeSelect 2. Psychosocial morbidity was assessed at baseline and each follow up using a mental health score, sexual attitude score, and perception of genital herpes score. RESULTS: Twenty-one percent (41 of 196) of participants tested positive for HSV-2 antibody. Among patients who were HSV-2-positive, there was no significant change in mental health score from baseline during either follow-up visit, nor was there any difference compared with persons who were HSV-2-negative. Patients who were HSV-2-positive did have a decline (P = 0.01) in their sexual attitude scores at the 1-week follow up compared with persons who were HSV-2-negative, indicating a decrease in positive sexual attitude, but this difference no longer remained at the 3-month follow up (P = 0.74). Patients who were HSV-2-positive viewed having genital herpes as significantly less traumatic than patients who were HSV-2-negative at both follow-up visits (P <0.01). CONCLUSION: There was no apparent lasting adverse psychosocial impact of detecting HSV-2 infection among individuals without a history of genital herpes seeking herpes testing at an STD clinic.     

Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic

Methods: Consecutive males were enrolled in a study of the epidemiology of GH. Consenting men answered questionnaires regarding their histories of possible GH and underwent serological testing for HSV-1 and HSV-2. Association statistics between response to each question and HSV-2 serological status were calculated. Results: Of 328 men enrolled, 148 (46%) had HSV-2 antibodies. 14 (4.3%) reported a history of GH when queried as part of a list of other STD (sensitivity (S) 0.08). 17 (5.2%) reported a history of GH when asked directly "Do you have genital herpes?" (S 0.09). 75 (21.1%) participants reported a history of a recurring genital sore, ulcer, or zipper cut (S 0.32). Overall, 64.2% of HSV-2 seropositive men answered "no" to all three questions. A "yes" response to any of the questions was only 36% sensitive for predicting HSV-2 infection. Conclusion: Few HSV-2 infected men report either a history of GH or are aware that they are infected. Asking about a history of recurrent genital sores was a more sensitive historical marker of HSV-2 infection than asking about a history of "genital herpes."