Epidemiologic determinants of herpes genitalis case detection rates among STD clinic attendees

ARTICLE

Auteur(s) : Kyriakos P. KYRIAKIS, Maria HADJIVASSILIOU, Helen PAPADOGEORGAKI, Vassilios A. PAPARIZOS, Andreas KATSAMBAS

University of Athens, Department of Dermatology and Venereology, “Andreas Sygros” Hospital, Reference Laboratory of STD and AIDS, Dragoumi 5, Kesariani, 16121 Athens, Greece.

Article accepted on 18/03/2003

Despite health education concerning sexually transmitted disease (STD)/AIDS prevention the worldwide prevalence of herpes genitalis continues to increase. The number of sufferers world-wide has been estimated at approximately 86 million people [1]. Much of this appears to be related to the chronicity of infection and high frequency of unrecognized infection [2]. Herpes simplex virus (HSV) genital infection clinical episodes occur on a chronic carrier state background where the treatment of active infection and immediate contact tracing have not proven effective in curbing the continued spread [3-5].
It is of interest that since 1990, an influx of about one million immigrants from Eastern Europe, Asia and Africa entered Greece. For this patient population in particular limitations of hospital studies include the influence of the behaviour of symptomatic participants with respect to obtaining treatment. It should be noted that to date, on a world-wide basis there is a concerted health education campaign regarding AIDS and STDs in general but without any specific messages for this viral genital infection.
In this seven year cross sectional hospital-based study (1990-96) we attempted to detect significant epidemiologic determinants associated with symptomatic case detection rate that might be useful for clinic or community based preventive interventions.

Methods

Symptomatic herpes genitalis infection diagnosis was based on clinical criteria (only first visit of all consecutive cases, males n = 715, females n = 116) which were subsequently ascertained by direct immunofluorescence. Although the clinical picture is not always specific direct immunofluorescence detects the presence of specific antigens in a sample by their ability to bind to fluorescent labelled reagent antibodies [6].
Incidence denominator and reference population of this cross-sectional hospital-based study consisted of 5,831 consecutive symptomatic patients classified in eleven STD entities (%): genital warts n = 2,988 (51.2), HSV genital infection n = 831 (14.2), male urethritis n = 403 (6.9), chlamydial genital infection n = 375 (6.4), gonorrhoea n = 369 (6.3), syphilis n = 288 (4.9), cervicitis n = 244 (4.2), pediculosis pubis n = 126 (2.2), trichomoniasis n = 95 (1.6), male proctitis n = 80 (1.4) and chancroid n = 32 (0.5); 4,734 men (81.2%) and 1,097 women (18.8%). The initial objective of this data collection was to investigate HIV seroprevalence in STD patients in the context of participation in a multi-centre study [7]. Eligible subjects were persons who had not been treated for any STD in the past 3 months. All participants answered a standardised questionnaire. Collected information regarded gender, age (years), nationality, educational level (i.e., no formal education, compulsory, post-compulsory and higher education), injecting drug use history (IDU), sexual orientation (heterosexuals and men having sex with men-MSM), and STD diagnosis. The reported number of sexual partners in the past six months (1, 2-4, 5-9, ≥ 10) was used as a marker of promiscuity level [8].
This study was carried out in “A. Sygros” hospital, which is the only public dermato-venereological hospital in the greater area of Athens and Piraeus totalling 4.5 million inhabitants. Representative data collection is ensured by the respective extended catchment area, increased attendance and the lack of inequalities in the access and the availability of health care services. In Greece, private STD hospitals or other services targeting specific population subgroups do not exist.
In the context of the STD reference population the combination of gender, nationality, sexual orientation and IDU history divided disease samples into 12 patient categories (Table I). Accordingly, their etiologic association with herpes genitalis morbidity was evaluated by appropriate stratified Mantel-Haenszel χ² analysis of the respective case detection rates. The respective odds ratios (ORs) were calculated and their Cornfield 95% confidence interval was evaluated [9, 10]. The contribution of sexual orientation was evaluated only between MSM and male heterosexuals.

Table I. Epidemiologic characteristics of herpes genitalis patient subgroups.

Within the herpes population, interrelations of the above variables were estimated using Pearson’s product-moment correlation. Cases with multiple STD diagnoses were counted more than once.

Results

The overall relative incidence of herpes was 14.2% (Table I), being the second most common STD. Clinically apparent herpes coexisted with condylomata (n = 38) and in one case with gonorrhoea. In 31 of these 39 cases (79.5%) it was an overlooked, comorbid, genital infection.
Overall in stratified analysis, herpes genitalis was more often detected in males (p = 0.0004), Greek patients (p < 10^-5), and male heterosexuals rather than MSM (p < 10^-7). As revealed by their lower significance level, these overall associations resulted only from significant differences in the incidence of the following strata-subgroups: by gender between Greek heterosexual men and women (χ^2, p < 10^-5, OR 1.7, Cornfield 95% CI 1.3-2.1) (Table I); by nationality between Greek and immigrant heterosexual men (χ^2, p < 10^-5, OR 2.4 Cornfield 95% CI 1.6-3.7); and by sexual orientation between Greek male heterosexuals and Greek MSM (χ², p < 10^-8, OR 2 Cornfield 95% CI 1.5-2.5). Differences in incidence of all the remaining subgroups were not significant.
The geographic origin of our immigrant outpatients was 21 (41.2%) from Eastern Europe, four (7.8%) Middle East, six (11.8%) Sub Saharan Africa and 20 (39.2%) from Asia.
In the context of STDs, injecting drug use was not found associated with the frequency of herpes genitalis diagnosis both in stratum specific and in the overall comparison (χ², stratified analysis).
Within our patient population the following significant correlates were detected (Pearson’s product moment correlation):
Herpes genitalis patient age was inversely associated with educational level (p < 0.0001) and the number of partners (p = 0.0002). There was not any association of gender, nationality, sexual orientation, promiscuity and IDU history with educational level. Women were younger (p < 0.0001) and less promiscuous (p = 0.03) than male cases. Immigrants were younger than Greek cases (p < 0.0001), reported a higher number of partners than Greeks (p < 0.0001), without significant quantitative differences by geographic origin and they were more frequently females (p = 0.005). Actually, in the HSV population, the overall men/women ratio revealed that immigrant women were five times more infected as compared with Greek women (41% vs. 12.1%, χ², p < 10^-8, OR 5, Cornfield 95% CI 2.7-9.5) (Table I). Homo/bisexuals were more likely to be older (p < 0.0001) and with more partners than heterosexuals (p = 0.0004). Cases eporting an injecting drug use history were more likely to be heterosexuals (p < 0.0001) and with few partners in the recent past (p < 0.0001).

Discussion

In accordance with previous observations, in the dominant population HSV genital infection at the time of healthcare seeking to the hospital was not associated with recent high risk sexual behaviour [11]. Herpes genitalis episodes are of short duration and thus low risk sexual behaviour reflected by low partner change rate and health education parameters contributed to a significantly more frequent diagnosis among less promiscuous and rather older STD clinic attendees irrespective of sexual orientation or other risk behaviour. Since the risk of acquiring herpes genitalis is higher in females, the lower case detection rate in Greek women compared to men possibly resulted from their low partner change rate and/or higher rates of asymptomatic or unrecognized infections in women [2, 3]. Low risk sexual behaviour of Greek male heterosexuals corresponds to previous observations that once knowing or told they have herpes genitalis, patients increase their condom use and the frequency of having sex during periods of lesions decreases [2, 3]. This low risk behaviour was detected mainly in herpes and condyloma STD outpatients whereas the opposite occurred in bacterial infections. Although partner selection was not qualitatively investigated, low risk behaviour and the absence of any significant association with low educational level which usually reflects a low socio-economic level indicates the lack of direct association with any HSV genital infection core group [8].
Within the herpes population, a higher case detection rate of immigrant women compared to Greek indicates a less protective behaviour in foreign networks. The estimated risk of a susceptible female contracting HSV from infected males is 80% following a single contact [12]. Moreover, countries with significant heterosexual HIV epidemics also appear to have rapidly increasing numbers of herpes genitalis cases [13]. In women, herpes genitalis diagnosis increased the probability of detecting a co-infection with HIV 8.7 times (95% CI 1.6-47, seropositivity rate 3.5%) in line with other reports and was due to four immigrants from Sub-Saharan Africa, whereas this did not apply in males [7, 12]. The lower incidence of herpes genitalis in male immigrant STD outpatients is consistent with findings from other European countries [11] since cultural and educational factors as well as economic refugee status-related contexts inhibit health seeking behaviour, despite free of charge STD health services [14].
As previously summarised by others, the number of sexual partners, irrespective of sexual orientation correlates directly with acquisition of HSV-2, which is usually acquired through sexual activity, whereas the highest prevalence of antibodies has been detected in MSM (83%) [12]. Thus, in our MSM with genital herpes older age, higher number of partners and the significantly lower outpatient incidence, suggest that this ulcerative STD is most often a neglected health problem resulting in a protracted chronic carrier state within a closed population.
The lack of any incidence association with IDU, though attributable to a delayed health seeking behaviour, is also in accordance with previous seroepidemiologic findings [15].
Since serological screening was not carried out, this study limitation precludes any further patient classification and virus type-related risk profile correlates. The percentage of herpes comorbid infections with other STDs might have been many times greater if all STD outpatients and especially the promiscuous were examined for subclinical or asymptomatic genital herpes [15].
Education, counselling and treatment of already non-promiscuous patients with HSV will effectively reduce disease-related and psychosocial complications as well as transmission among their future partners [2, 3]. Regarding the protective value of condom, others have shown that the condom offers significant protection in susceptible women in conjunction with counselling about avoiding sex when a partner has lesions [16]. Actually, when herpes discordant couples are aware of the infected person’s infection, sexual transmission to the uninfected partner is substantially less frequent than in couples who are unaware that one person is infected [17]. Apart from the indigenous population, for immigrant outpatients there is need for health education pamphlets, in their own language, targeting transmission, the bi-directional protection provided by condoms and about dealing with and recognising recurrences. However, the impact of preventive interventions with regard to former partner notification is difficult to evaluate.n

References

1. Halioua B, Malkin JE. Epidemiology of genital herpes-recent advances. Eur J Dermatol 1999; 9: 177-84.

2. Corey L. The current trend in genital herpes. Progress in prevention. Sex Transm Dis 1994; 21: S38-S44.

3. Corey L. Raising the consciousness for identifying and controlling viral STDs: fears and frustrations. Sex Transm Dis 1998; 25: 58-69.

4. Aral SO, Holmes KK. Epidemiology of sexually transmitted diseases. In Holmes KK, Mardh PA, Sparling PK, Wiesner PJ (eds): Sexually Transmitted Diseases, NY: McGraw Hill Publishers, 1989; 125-141.

5. Hart G. Risk profiles and epidemiologic interrelationships of sexually transmitted diseases. Sex Transm Dis 1993; 20: 126-36.

6. Chopra KF, Lee PC, Tyring SK. Introduction to virus infections. In Demis J (ed) Clinical Dermatology, 25^th revision 1998, Lippincott-Raven Publishers, Philadelphia, vol. 3, chapter 14-0.

7. Kyriakis KP, Hadjivassiliou M. HIV-1 infection associated risk factors among sexually transmitted disease patients in Athens, Greece: 1990-96. Sex Transm Dis 2000; 27: 259-65.

8. Catchpole MA. The role of epidemiology and surveillance systems in the control of sexually transmitted diseases. Genitourin Med 1996; 72: 321-9.

9. Dean AG, Zubieta JC, Sullivan KM, Delhumeau C (eds). Manual of EpiInfo^TM 2000. Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 2000.

10. Rothman KJ. Modern Epidemiology. Little Brown and Co USA; Stratified Analysis: 1986; 177-236.

11. Hughes G, Catchpole M, Rogers PA et al. Comparison of risk factors for four sexually transmitted infections: results from a study of attenders at three genitourinary medicine clinics in England. Sex Transm Inf 2000; 76: 262-267.

12. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Dis 1998; 26: 541-53.

13. O’Farrel N. Increasing prevalence of genital herpes in developing countries: implications for heterosexual HIV transmission and STI control programmes. Sex Transm Inf 1999; 75: 377-84.

14. Marmot MG, Kogevinas M, Elston M. Social/economic status and disease. Annu Rev Public Health 1987; 8: 111-35.

15. Austin H, Macaluso M, Nahmias A, et al. Correlates of herpes simplex virus seroprevalence among women attending a sexually transmitted disease clinic. Sex Transm Dis 1999; 26: 329-34.

16. Wald A, Langenberg AG, Link K, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA 2001; 285: 3100-6.

17. Highlights from the 2002 STD conference: Genital herpes: the increasing role of HSV-1,prevention by condoms and serologic screening. http:// medscape. com/viewarticle/4331484.