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.     

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.     

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.     

Prevalence and determinants of herpes simplex virus type 2 infection in a cohort of HIV-positive individuals in Italy

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infections may be a risk factor for the transmission of HIV. Data on the prevalence of HSV-2 infection among HIV-positive individuals are scarce. GOAL: The goal was to study the seroprevalence of and risk factors for HSV-2 infection among a cohort of Italian HIV-positive individuals. STUDY DESIGN: This was a cross-sectional study. HSV-2 serologic testing was performed for individuals with known date of HIV seroconversion, on the serum specimen obtained on the date closest to the estimated date of seroconversion. Antibodies to HSV-2 (anti-HSV-2) were detected by a gG2-specific ELISA. RESULTS: A total of 380 HIV-positive individuals were tested for anti-HSV-2; 126 (33.2%) of them were positive. Older age at HIV seroconversion and homosexuality were significantly associated with HSV-2 infection in the multivariate analysis. CONCLUSIONS: These data stress the need for including anti-HSV-2 testing and therapy in the management of HIV positivity, especially for reducing the risk of transmission of HIV through herpetic lesions.     

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.     

Seroprevalence of herpes simplex virus type 2 infection among attendees of a sexually transmitted disease clinic in Italy. Italian Herpes Forum

BACKGROUND AND OBJECTIVES: An increased prevalence of herpes simplex virus type 2 (HSV-2) infection has been recently observed in industrialized countries. GOAL: To determine HSV-2 seroprevalence in a high-risk population in Italy. STUDY DESIGN: A cross-sectional study was performed to ascertain the HSV-2 prevalence among 919 persons attending an STD clinic in northern Italy. A HSV-2-specific glycoprotein G-2-based immunoglobulin G enzyme-linked immunoabsorbent assay (Gull/Meridian ELISA; Meridian Diagnostics, Cincinnati, OH) was used and validated against Western blot analysis. RESULTS: A prevalence of 24.6% was found without differences between males and females. Seroprevalence increased with age and number of partners during the previous year. Compared with Western blot analysis, the Gull/Meridian ELISA showed a sensitivity of 91.9% and a specificity of 98%, and positive and negative predictive values of 93.9% and 97.4%, respectively. CONCLUSION: This is the first Italian survey of HSV-2 infection conducted with a properly validated, Food and Drug Administration-approved, type-specific serologic method in a high-risk population. It is likely that between one to three million adults are infected with HSV-2.     

Ocular herpes simplex virus infections

Eye infection with herpes simplex virus is the single most common cause of corneal blindness in the United States and other industrialized countries. It occurs as often in developing countries. Herpetic eye disease presents a unique set of clinical problems, and there is considerable controversy even among knowledgeable ophthalmologists on the management of this disease.Like herpes simplex infections elsewhere, ocular herpetic infections are usually recurrent. While the disease often attacks the epithelial tissues of the lids, conjunctiva, and cornea, it can also involve the connective tissue of the cornea and interior structures of the eye. Most of the herpes isolates from the eye have been type 1, with only a low percentage of type 2 isolates.^1,2     

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe

OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. METHODS: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. RESULTS: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and 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.     

Oral shedding of herpes simplex virus type 2

OBJECTIVES: Herpes simplex virus (HSV) 1 and HSV-2 reactivate preferentially in the oral and genital area, respectively. We aimed to define frequency and characteristics associated with oral shedding of HSV-2. METHODS: Demographic, clinical and laboratory data of patients with documented HSV-2 infection and at least one oral viral culture obtained were selected from the University of Washington Virology Research Clinic database. RESULTS: Of 1388 people meeting the entry criteria, 44 (3.2%) had HSV-2 isolated at least once from their mouths. In comparison with the 1344 people who did not have HSV-2 isolated from their mouth, participants with oral HSV-2 were more likely to be male (OR = 1.9, 95% CI 1.0 to 3.7), HIV positive (OR = 2.9, 95% CI 1.4 to 6.0), and homosexual (OR = 2.2, 95% CI 1.1 to 4.2), and to have collected a larger number of oral specimens (median 32 v 4, p<0.001). Of the 58 days with oral HSV-2 isolation, 15 (25%) occurred during newly acquired HSV-2 infection, 12 (21%) during a recurrence with genital lesions, three (5%) during a recurrence with oral lesions, and three (5%) during a recurrence with oral and genital lesions; 25 (43%) occurred during asymptomatic shedding. Oral HSV-2 was found less frequently than oral HSV-1 (0.06% v 1%, p<0.001) in people with HSV-1 and HSV-2 antibody, and less frequently than genital HSV-2 (0.09% v 7%, p<0.001). CONCLUSIONS: Oral reactivation of HSV-2 as defined by viral isolation is uncommon and usually occurs in the setting of first episode of genital HSV-2 or during genital recurrence of HSV-2.     

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.