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.     

Sequential genital infections by herpes simplex viruses types 1 and 2: restriction nuclease analyses of viruses from recurrent infections

Virus isolated from a woman presenting with the first symptomatic episode of genital herpes was identified as herpes simplex virus type 1 (HSV-1) by restriction nuclease fingerprinting. Testing for IgM antibody to HSV indicated that the patient had recently contracted a new HSV infection. Virus microneutralization and the micro-solid phase radioimmunometric test for IgG, however, showed that the patient had had prior infection with herpes simplex virus type 2 (HSV-2); thus the HSV-1 infection was acquired despite the presence of antibody to HSV-2. Genital herpes recurred about four, seven, and nine months after the HSV-1 infection. Isolates from the latter three episodes all were of an identical strain of HSV-2 and were not recombinants or a mixture of the viruses. The data show that two distinctly different herpes simplex viruses can initiate genital infections in one individual and suggest that HSV-2 is more likely to recur than HSV-1.     

Is HSV serology useful for the management of first episode genital herpes?

BACKGROUND: First episode genital herpes simplex virus (HSV) infections can be classified into three groups, primary genital herpes (no previous exposure to HSV), non-primary first episode (IgG antibody to HSV of the non-presenting type), and first episode with pre-existing IgG HSV antibodies. The use of IgM to classify first episode genital herpes has not been evaluated. OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HSV-1 and HSV-2 IgM antibodies for the diagnosis of first episode genital herpes, when compared with clinical diagnosis. METHODS: Patients with a first clinical episode of genital herpes were recruited. Sera were tested for IgG antibodies to HSV-2 using an indirect enzyme linked immunosorbent assay (ELISA). Equivocal results were resolved by western blot. HSV-1 IgG and IgM and HSV-2 IgM antibodies were detected using western blot. RESULTS: 157 patients were recruited. 31 were excluded (missing data or no detectable antibodies and negative viral isolation). Therefore, 126 patients were included in the analysis. 23 (18.3%) had primary genital herpes, 34 (27.0%) non-primary first episode, and 69 (54.8%) had pre-existing genital herpes. The specificity and PPV of HSV IgM was 100%; the sensitivity was 79% and the NPV 85%. CONCLUSION: IgM HSV serology may be useful in the management of some patients with first episode genital herpes and provide an indication of the source of infection. Drawbacks include the low sensitivity and NPV, lack of availability, IgM antibodies may occasionally be produced in response to recurrent infection and, finally, IgM antibodies may take up to 10 days to develop and last 7-10 days.     

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.     

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.     

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.     

Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.

Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.     

Detection of varicella zoster virus in genital specimens using a multiplex polymerase chain reaction

OBJECTIVE: To compare the relative proportions of varicella zoster virus (VZV) and herpes simplex viruses in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection. METHODS: Swabs of genital lesions from 6210 patients attending general practices, infectious diseases clinics within hospitals, or sexual health centres for treatment of their genital lesions were tested using polymerase chain reaction (PCR) technology. The multiplexed PCR was capable of detecting herpes simplex virus types 1 and 2 (HSV-1, HSV-2), VZV, and cytomegalovirus in a single sample. RESULTS: A total of 2225 patients had viruses detected by PCR. HSV-1 was detected in 36%, HSV-2 in 61%, and VZV in 2.9% of PCR positive samples. Of the 65 patients with VZV genital infection, many were thought to have HSV infection before laboratory testing. CONCLUSIONS: The finding of VZV in nearly 3% of virus positive genital specimens demonstrates that this virus needs to be considered as a differential diagnosis for genital herpetic lesions. Advice provided to patients with VZV genital infection regarding the source of infection, likelihood of recurrence, and potential for transmission of the virus will be different from that given to patients with HSV infection.     

Herpes simplex virus type 2 (HSV-2) Western blot confirmatory testing among men testing positive for HSV-2 using the focus enzyme-linked immunosorbent assay in a sexually transmitted disease clinic

OBJECTIVE: The objective of this study was to define the positive predictive value (PPV) of the Focus herpes simplex virus type 2 (HSV-2) enzyme-linked immunosorbent assay (ELISA) in a low HSV-2 prevalence population and to develop a new test interpretation algorithm. METHODS: HSV-2 Western blots were performed on sera from male sexually transmitted disease clinic patients testing HSV-2 ELISA-positive and used to define a new class of indeterminate HSV-2 ELISA result. HSV-2 Western blots were then prospectively performed on sequential sera with indeterminate HSV-2 ELISAs. RESULTS: Ninety-one (84%) of 108 HSV-2 ELISA-positive sera tested HSV-2 Western blot-positive. Western blot positivity was more common in men without herpes simplex virus type 1 (HSV-1) antibody than in those with HSV-1 antibody (93% vs 76%, P = 0.02) and in men with a history or clinical evidence of genital lesions (88% vs 80%, P = 0.30). Selectively raising the ELISA index value defining HSV-2 positivity from >1.1 to >or=3.0 either among HSV-1-positive men or among those without a history or clinical evidence of genital lesions increased the PPV to >or=93%. Prospective evaluation of an algorithm incorporating HSV-1 serostatus found that 11 of 70 persons with indeterminate HSV-2 ELISAs were Western blot-positive. CONCLUSIONS: Clinicians should consider selectively using a higher index value to define Focus ELISA HSV-2 positivity based on either HSV-1 serostatus or clinical circumstances.     

生殖器疱疹患者530例HSV抗体型别检测分析

目的了解生殖器疱疹患者HSV-1和HSV-2的感染情况,并分析生殖器疱疹的流行特点。方法采用酶联免疫吸附试验(ELISA)法对性病门诊530例临床诊断为生殖器疱疹的患者进行了HSV血清抗体检测。结果 530例中男311例(58.68%),女219例(41.32%)。HSV-1IgM抗体阳性60例(11.32%),HSV-1IgG抗体阳性471例(88.87%),HSV-2IgM抗体阳性213例(40.19%),HSV-2IgG抗体阳性349例(65.85%)。年龄以31～40岁最多,为210例,其次为21～30岁194例。职业中最多的是自由职业和民工。初发者304例(57.36%),复发者226例(42.64%),其中频繁发作(≥6次/年)85例(16.04%)。结论长春地区生殖器疱疹患者以HSV-2感染为主。女性近期感染多于男性。以21～40岁性活跃人群为高发年龄组。     

女性原发性生殖器疱疹中HSV-Ⅱ的检测及意义

目的探讨单纯疱疹病毒Ⅱ型(HSV-Ⅱ)与女性原发性生殖器疱疹(GH)的相关性及意义。方法应用酶联免疫吸附法(ELISA)分别检测患者血清中HSV-Ⅱ抗体以及分泌物中的HSV-Ⅱ抗原。结果HSV-Ⅱ中IgG均阴性的138例女性生殖器疱疹患者中HSV-Ⅱ抗原阳性78例(56.52%);HSV-Ⅱ中IgM抗体阳性130例(94.20%),抗体阳性率明显高于抗原阳性率(P<0.01)。典型病例组抗原阳性65例(87.84%),IgM抗体阳性66例(89.19%);不典型病例组抗原阳性13例(20.31%),IgM抗体阳性64例(100.00%)。结论对于皮损时间短,症状典型者可检测HSV-Ⅱ抗原;皮损时间长,或反复者可检测HSV-Ⅱ抗体,可以有效提高HSV感染的临床诊断率。     

汕头市孕妇生殖器疱疹血清流行病学初步调查研究

目的：调查汕头市不同年龄段、不同孕期、不同妊娠史和不同职业孕妇血清中HSV-2特异性抗体IgG的存在情况。方法：随机选取汕头市520例无症状的正常孕妇进行研究，采用酶联免疫吸附法（ELISA）检测孕妇血清中HSV-2特异性抗体IgG。结果：共调查520例孕妇，阳性率为26．2％（136／520），不同孕期感染率无显著性差异；年龄在26～35岁孕妇、有异常妊娠史、文化程度低的孕妇HSV感染的危险性高。结论：孕妇HSV-2感染率高，对孕妇进行HSV-2感染的血清学监测，有利于识别有生殖器疱疹危险因素的孕妇和亚临床型孕妇，降低漏诊率，对预防新生儿HSV感染、降低流产、早产和死产的发生具有十分重要的意义。     

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.     

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.     

Prevalence of serum antibodies to herpes simplex virus types 1 and 2: application of an ELISA technique to 100 cases of anogenital herpes

Sera of 100 patients affected by anogenital herpes were tested by an enzyme-linked immunosorbent assay (ELISA) technique using partially purified antigens obtained by extraction from the nuclei of infected Vero cells. Herpes simplex virus type 1 (HSV-1) was isolated from the anogenital lesions of 17 patients and herpes simplex virus type 2 (HSV-2) from 83 patients. The relative proportions of antibody of the IgG class to HSV-1 and HSV-2 were determined and their ratio (R) was calculated, except for 23 patients for whom the corrected optical density (COD) obtained for HSV-1 or HSV-2 antibody was less than the lower value limit of 0.025. A predominance of HSV-2 antibody (R less than 1) was found in 40 patients and was uniformly associated with isolation of HSV-2, whereas a predominance of HSV-1 antibody (R greater than 1) in 37 patients was found in the presence of infection with HSV-1 in 11 (30%) and with HSV-2 in 26 (70%) patients. This study also confirms the association of a higher frequency of recurrences with HSV-2: among the 55 patients with recurrent herpes, those from whom HSV-2 was isolated had a history of more recurrences than those infected with HSV-1 (P less than 0.05; Mann and Whitney's nonparametric test). No correlation between the number of recurrences and the level of HSV-2 antibody was found.     

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 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.     

The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes

OBJECTIVE: To measure the burden of infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) in the general population of England and Wales and to assess temporal changes in the incidence of HSV-1 infection in childhood. METHODS: 4930 residual blood samples taken from people aged 0-69 years and submitted to 15 public health laboratories in England and Wales between January 1994 and June 1995, and 500 samples taken from people aged 10-14 years between November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV-2 using type specific ELISA assays. RESULTS: The prevalence of antibody to HSV-1 in 10-14 year olds declined from 34% in samples collected in 1986-7 to 24% in samples collected in 1994-5 (p < 0.001). HSV-1 antibody prevalence in adults increased with age and was higher in females than males, reaching 54% in females aged 25-30 years in 1994-5. In samples collected in 1994-5 from people aged 16-69 years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women. CONCLUSIONS: The incidence of HSV-1 infection in childhood is falling in England and Wales. The prevalence of HSV-2 infection in the general population is low, with the rate of infection significantly lower than that described for the general population in the United States and developing countries. The falling rate of HSV-1 infection in childhood may be one factor contributing to the increasing incidence of genital HSV-1 infection.     

单纯疱疹病毒2型DNA疫苗对豚鼠抗病毒感染的研究

目的 探讨单纯疱疹病毒2型DNA疫苗的抗病毒感染效应.方法 重组DNA疫苗pcgD免疫雌性豚鼠,采用血清中和实验检测抗体,单纯疱疹病毒2型(HSV-2)sav株接种豚鼠,观察DNA疫苗保护动物抵抗HSV-2病毒感染的能力.结果 pc-gD免疫豚鼠产生的中和抗体效价远远高于对照组和生理盐水组,感染病毒后,表现出初发感染推迟,复发感染的严重程度下降.结论 DNA疫苗能有效地保护动物免受HSV-2病毒的攻击,延缓初发感染,减少复发感染.     

The psychosocial impact of serological herpes simplex type 2 testing in an urban HIV clinic

BACKGROUND/OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is a common infection among HIV infected people. HSV type specific serologies permit the diagnosis of previously unrecognised HSV-2 infection. While substantial psychosocial morbidity has been associated with a clinical diagnosis of genital herpes, the burden associated with a serological diagnosis of HSV-2 is unclear. This study prospectively measured the psychosocial response to a new serological HSV-2 diagnosis in patients receiving care at an urban HIV clinic. METHODS: At entry, sera were tested for HSV-1 and HSV-2 antibodies by western blot. Participants completed a 90 item psychosocial and life quality questionnaire at enrollment, and at 2 weeks, 3 months, and 6 months after receiving test results. RESULTS: Of 248 HIV infected participants, 172 (69.4%) were HSV-2 seropositive and 116 (67.4%) seropositive people did not have a previous history of genital herpes. After correction for multiple comparisons, no statistically significant differences were detected on the psychosocial and life quality scales between those who received a new HSV-2 serological diagnosis compared with those who were HSV-2 seropositive with a history of genital herpes, or those who tested HSV-2 seronegative. Additionally, no significant changes in scores were observed during follow up. CONCLUSIONS: HSV-2 was a common but often unrecognised infection in this urban HIV clinic and participants coped well with a positive HSV-2 result. Concerns about psychosocial burden should not deter serological testing for HSV-2. Given the epidemiological and clinical interaction between HSV-2 and HIV, these data support routine HSV-2 testing of HIV infected people.