Emergence of herpes simplex type 1 as the main cause of recurrent genital ulcerative disease in women in Northern Ireland

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Abstract

Background: Genital herpes is a common infection affecting some 20% of sexually active people. Although herpes simplex virus (HSV) types 1 and 2 can both establish genital latency, reactivation from the sacral ganglia favours HSV-2. Over the past decade the incidence of type 1 genital infection in women has greatly increased. Objectives: To determine whether the increased prevalence of HSV-1 genital infection was benign or influencing the pattern of virus recovery in recurrent infection. Study design: A retrospective analysis of laboratory computer records was undertaken. Patients attending six genitourinary medicine (GUM) departments, over an 80 months period, were identified. Recurrent infection was confirmed where virus was recovered from at least two separate episodes of genital ulceration that were separated by an interval of 12 or more weeks. Episodes were further analysed for frequency, age, gender and virus type. Results: Sixty nine patients with recurrent genital herpetic infection were identified. HSV-1 and HSV-2 were predominantly recovered from recurrent genital infections in females (34 HSV-1 vs. ten HSV-2) and males (one HSV-1 vs. 24 HSV-2), respectively (P>0.001). The mean age of females and males, at the initial diagnosis, was 26 and 39 years. There was no difference in the recurrence rate by type. Conclusions: HSV-1 has become the commonest cause of recurrent genital ulceration in Northern Ireland, almost entirely due its recent increased prevalence in women over the last decade. Women are experiencing genital herpetic infections at an earlier age than men.

Introduction

Genital herpes is one of the commonest sexually transmitted diseases, affecting some 20% of sexually active people, with up to 80% of cases remaining undiagnosed (Tetrault and Boivin, 2000). The link between genital ulceration and the spread of human immunodeficiency virus (HIV) further underlines its importance (Schacker et al., 1998, Steen, 2001, Keet et al., 1990, Wald and Link, 2002). Asymptomatic shedding in the genesis of herpetic genital ulcerative disease (GUD) is also increasingly recognised (Mead et al., 1991, Raguin and Malkin, 1997, Barton et al., 1987). Where clinical disease is absent, type specific antibody tests have confirmed sub-clinical infection (Wald et al., 2000) and have proven useful for counselling discordant couples, especially during pregnancy (Kulhanjian et al., 1992). Type specific antibody tests confirm up to 10% of persons with adjudged first episode genital herpes to have already acquired herpes simplex virus type 2 (HSV-2) infection (Diamond et al., 1999). First episodes may, therefore, represent either primary or recurrent infection. Superinfection with a second virus type is possible but uncommon (Sucato et al., 1998) while reinfection with new genotypes has not been definitively proven.

Although both viruses can establish latency relative to the genital region (Sucato et al., 1998), trigeminal and sacral ganglia associated reactivations are skewed to type 1 and type 2 virus, respectively (Baringer, 1976). The extent and frequency of recurrent genital herpes is highly type specific, with HSV-2 reactivations outpacing HSV-1 by an order of three to one (Lafferty et al., 1987). While the dominant role of HSV-2 in genital herpes has long been well recognised, that attributable to herpes simplex virus type 1 (HSV-1) has also shown dramatic increases over the past 10–15 years (Raguin and Malkin, 1997). Reports from America (Ribes et al., 2001), Norway (Nilsen and Myrmel, 2000), Sweden (Lowhagen et al., 2000), Japan (Kawana, 2000) and Great Britain (Scoular et al., 1990, Tayal and Pattman, 1994) reflect the global nature of this change. Despite this the role of HSV-1 in recurrent GUD has apparently remained unaltered, with HSV-2 remaining the dominant agent (Drake et al., 2000, Kawana, 2000, Lowhagen et al., 2001). Thus in spite of the changing burden of HSV-1 genital infection, HSV-2 rather than HSV-1 appears predisposed to active latency in relation to the genital tract (Kawana, 2000).

In Northern Ireland HSV-2 was reported as the commonest type associated with GUD between 1982 and 1984 (Lavery et al., 1986) but by 1995 through 1999 it had been overtaken by HSV-1 (Christie et al., 1997, Coyle et al., 2001a, Coyle et al., 2001b). In the light of the sustained shift of disease burden from HSV-2 to HSV-1 over the past decade, we sought to determine if the change was benign or influencing the pattern of virus recovery in recurrent GUD. For enhanced clarity the study was restricted to patients where HSV-1 and/or HSV-2 was sequentially recovered from genital lesions.

Section snippets

Retrospective laboratory data analysis of genital ulcerative disease

Virus type and gender prevalence in recurrent GUD was investigated by a retrospective data analysis of laboratory results over an 80 months period. A data set retrieval was undertaken for the period 1st January 1995–31st August 2001 using the relational database paradox version 4.0 (Borland International, Scotts Valley, CA, USA) and involved the interrogation of 359 398 computer records. Searches selected out patient episodes where specimens from GUD were tested for HSV infection. Only patients

Statistical analysis

Non parametric tests were used to compare the results of: (a) gender association with HSV type recovered; (b) HSV type with method of test; (c) recurrence rates associated with the virus type; (d) the age when the first genital episode was confirmed for each virus type; (e) the gender association with each virus type. Significance was achieved at a P value of <0.05 using a two-sided test.

Retrospective data analysis

A total of 4564 specimens, submitted from six GUM clinics, were tested for HSV infection over the 80 months period of the study. HSV was recovered from 1114 of 4564 specimens (24%) received from 1002 patients, confirming herpetic genital infection. HSV was recovered from a number of anatomical sites including the perineum, cervix, penis (including glans, prepuce and shaft), urethra (both male and female), vagina, vulva, buttock and thigh; only HSV-2 was recovered from buttock and thigh

Discussion

To address if the recently recognised increased prevalence of HSV-1 in genital infections was influencing the pattern in recurrence, we sought to establish unequivocal evidence of recurrent herpetic infection using strict diagnostic criteria including: (a) two or more laboratory confirmed HSV genital infections; (b) an interval of at least 12 weeks between the infections. The results confirmed that in Northern Ireland HSV-1 has replaced HSV-2 as the commonest type recovered from recurrent GUD,

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