Epidemiology of Genital Herpes Simplex Virus Type 1 and 2 Infections in Southwestern Finland During a 10-Year Period (2003–2012)

Abstract

Background 

The objective of this study was to analyze the proportion of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in genital infections during a 10-year period (2003–2012) among outpatients of a clinic of sexually transmitted disease in Southwestern Finland.

Methods 

We analyzed prospectively the proportion of HSV-1– or HSV-2–positive culture samples from our sexually transmitted disease clinic outpatients with genital herpes infection during the years 2003 to 2012 and compared the proportions of positive HSV-1 and HSV-2 findings with the age and sex of the patients.

Results 

Herpes simplex virus type 2 was typed in 66.4% (557/839) and HSV-1 in 33.6% (282/839) of the patients during the entire study period. The mean age of male patients (26.3 years) with a laboratory-confirmed HSV-1 infection was significantly lower than that in male patients with an HSV-2 infection in 2003 to 2007 (26.3 vs. 32.9 years), with P < 0.0001, and (28.6 vs. 34.0) P < 0.0019 in 2008 to 2012, respectively. More female than male patients had HSV-1 infection; in the first study period (2003–2007), 58% were female, and in 2008 to 2012, it was again 63.6%. There was no significant difference between the age of female patients with HSV-1 and those with HSV-2.

Conclusions 

Herpes simplex virus type 2 was still the most common causative agent of genital herpes in Southwestern Finland, but the proportion of HSV-1 was increasingly high. The age difference between male patients with HSV-1 and HSV-2 narrowed during the years studied.

In Brief

Herpes simplex virus type 2 (HSV-2) was the most common causative agent of genital herpes infections in Southwestern Finland during the years 2003 to 2012, but the number of HSV-1 infections still remained high. Most patients with HSV-1 infection were female.

The percentage of herpes simplex virus type 1 (HSV-1) in new diagnosed genital herpes infections has been shown to be increasingly high in developed countries.^1–13 Virus type and the age of acquisition of primary infection are thought to influence the severity of HSV infection.^5,6 We have earlier, in 1994 to 2002, shown an increase in the proportion of genital infections caused by HSV-1 and a decrease in the age of male patients with HSV-1 infection in the same study population in an outpatient clinic in Southwestern Finland.¹⁴ In this report, we have studied the epidemiology of first symptomatic genital herpes infections during a 10-year period (2003–2012).

MATERIALS AND METHODS

Patients and Methods

The Department of Venereological Diseases at Turku University Central Hospital has provided venereologic services for decades. The clinic for the sexually transmitted diseases (STDs) has served approximately 250,000 persons from area in and around Turku city. Patients may seek medical treatment of STD free of charge without a referral on weekdays. In most cases, the patients visit the Venereological Department during the first symptomatic episode of suspected genital herpes, that is, blisters or ulcers in the genital region. From all patients who obtain a clinical diagnosis of genital herpes, a virus culture analysis is performed only on their first symptomatic visit to confirm the viral etiology of the disease.

In 2005 to 2012, Virus Diagnostic Laboratory, University of Turku, performed 1762 rapid virus culture tests from swab samples from genital lesions. Owing to change in patient laboratory data collection system, the total number of samples tested by rapid virus culture before the year 2005 was not available. The number of patients tested annually, HSV cultures, and the positive samples in 2005 to 2012 are presented in Table 1. No changes were made in the methodology of collection of laboratory specimens or rapid virus culture techniques during the study period. The samples for virus culture tests were taken of suspected genital herpes lesions by sterile cotton swabs, which were placed in vials containing 2 mL viral transport medium (5% tryptone phosphate broth, 0.5% bovine serum albumin, and antibiotics in phosphate-buffered saline). The samples were stored at −4°C overnight and transported to the virus laboratory, where inoculation of the samples was performed on the same day. Rapid virus culture and typing with monoclonal antibodies against HSV-1 or HSV-2 were performed as previously described.^14,15 The study was ethically approved by the joined committee of Turku University and Turku University Hospital.

TABLE 1: Numbers and Mean Ages (in Years) and HSV Cultures of STD Clinic Patients From 2003 to 2012

Statistics

A 2-tailed 2-sample unequal variance Student t test was used. P values less than 0.05 were considered statistically significant.

RESULTS

Epidemiogical Aspects

Altogether, 37,896 patients attended the STD clinic during the period from 2003 to 2012 (Table 1). A total of 51% of the patients were male and 49% were female. In this study, the proportion of male and female patients remained consistent each year, and the mean age of patients unchanged during the study period.

A positive result from a rapid virus cultivation test for HSV was detected from 839 patients (Tables 2 and 3). Of these, 453 (54.0%) were from female patients and 385 (46.0%) were from male patients. The total number of herpes cases per annum varied between 64 and 103. The mean age of all patients with a laboratory-confirmed HSV was 29.2 years: 27.0 and 31.7 years for the female and male patients, respectively. The age and sex of the patients with a positive result and proportions of HSV-1 and HSV-2 isolates during the periods from 2003 to 2007 and 2008 to 2012 are presented in Tables 2 and 3. Of the total 839 samples, HSV-2 was typed in 66.4% (557/839) and HSV-1 in 33.6% (282/839) of the specimens. Of these, in 2003 to 2007, in the 418 HSV-positive samples, HSV-2 was typed in 68.7% (287/418) and HSV-1 in 31.3% (131/418). Again, during the latter study period (2008–2012), of the total of 421 HSV-positive samples, HSV-2 was detected in 64.1% (270/421) and HSV-1 in 35.9% (151/421). During the whole 10-year study period, the percentage of HSV-1 and HSV-2 infections detected of all confirmed genital herpes cases varied from 61.1% to 76.9% for HSV-2 and from 23.1% to 37.2% for HSV-1.

TABLE 2: HSV-Positive Cultures of STD Clinic Patients From 2003 to 2007

TABLE 3: HSV-Positive Cultures of STD Clinic Patients From 2008 to 2012

Most patients with HSV-2 infection (53.3%) in 2003 to 2007 were male, whereas in 2008 to 2012, they were female (54.4%). Moreover, patients with HSV-1 were female in both 2003 to 2007 (58%) and 2008 to 2012 (63.6%). During the both 5-year periods, the mean age of male patients with a laboratory-confirmed HSV-1 infection was significantly lower than that of those with an HSV-2 infection: 26.3 years versus 32.9 years (P < 0.0001) in 2003 to 2007 and 28.6 years versus 34.0 years (P < 0.0019) in 2008 to 2012. The mean age of male patients with HSV-2 infection was significantly higher than that of female patients with HSV-2 infection during both 5-year periods: P < 0.0001 in 2003 to 2007 and P < 0.0049 in 2008 to 2012.

DISCUSSION

In Finland, the seroprevalence of HSV-1 has been reported to be 52% and 13% for HSV-2 in the periods from 1989 to 2000.¹⁶ Seventeen percent of 8-year-old children¹⁷ and less than 50% of students¹⁸ have been shown to be HSV seropositive. In the light of our findings, it is tempting to speculate, that there is a growing young population that develops a genital herpes as a result of the primary HSV infection. Because serological tests were not performed for this study, it is not known whether the studied patients had been disposed to HSV earlier. This is an apparent flaw in this study.

In previous decades, genital herpes was primarily caused by HSV-2, but during the current century, the proportion of HSV-1 as a causative agent of genital herpes has increased in many developed countries.^1–13 In our earlier studies, during the period from 1994 to 2002, the proportion of HSV-1 was 20.7%, and in the current study, during the period from 2003 to 2012, it had increased to 33.6%. In some recent studies, HSV-1 has been shown to be the predominant type of HSV during primary infection.^1,19 Our previous study suggested that men acquire genital HSV-1 infection at an earlier age compared with HSV-2 infection in genital area.¹⁴ This finding was confirmed also in the current study. For the period from 2003 to 2012, the HSV-1–positive women outnumbered men with HSV-1 infection.

There is some published evidence of a partial protective function of HSV-2 infection against an HSV-1 infection²⁰ but not the opposite.^11,20 Herpes simplex virus type 2 has been shown to be the second common cause of aseptic meningitis and the most common cause of relapsing aseptic meningitis in Finland, whereas HSV-1 is mainly detected in encephalitis cases.²¹ It is not known which factors influence this, but localization of virus latency most probably affects the anatomical site and clinical manifestation of reactivations. Because HSV-1 is known to be reactivated less often than HSV-2, it can be assumed that latency of HSV-1 in sacral ganglions might lead to a decrease in meningitis cases caused by HSV. There is some evidence that HSV-1 might lead to neonatal herpes more often than HSV-2.²² The future will tell whether the increase in the proportion of HSV-1 genital herpes influences the incidence of neonatal herpes.

The authors are aware that there are limitations in this study. There is lack of clinical data to determine whether the patients had experienced prior HSV infection before their first visit to the study clinic. Also, no serological data are available to determine whether these were primary or nonprimary episodes, or first recurrent infections. Because the clinic operates on a self-referral basis, and patients are predominantly from areas around a university town, they may not be representative of the entire Finnish population.

In conclusion, we demonstrated that in 2003 to 2012, HSV-2 infection remained the most common cause of genital herpes in Southwestern Finland. However, the proportion of HSV-1 infections has increased since 2003 to 2007 in this study population in the latter half of this study period in 2008 to 2012. Together with our earlier study, we now have unique data for genital HSV type specificity from the same area for a period of 15 years.