Recurrent genital herpes: what are the predictable factors, and what more can be done?

A. A. Opaneye,(1) Vicki Ashton(2)
(1) Dept of Genitourinary Medicine, Middlesbrough General Hospital, Ayresome Green Lane, Middlesbrough, TS5 5AZ;
(2) Medical Statistics, University of Teesside, Middlesbrough.

Key words: genital herpes simplex, recurrences, immune modulators, vaccines

Introduction
Following a genital infection with herpes simplex virus (HSV) people present with a primary disease in the symptomatic group. The infecting virus may be type 1 or type 2. After the initial disease, there follows a period of latency when the virus resides in the sacral ganglia. Periodically, there is a reactivation of the virus and the patient suffers a recurrence. This may be symptomatic or on many occasions, it is asymptomatic. The diagnosis of HSV infection may be done by history and clinical examination, by serology to determine the presence of HSV antibodies or by tissue culture. The commonest method is by tissue culture and viral typing. The use of highly sensitive techniques has revealed that up to 80% of HSV-2 seropositive patients shed the virus from their genital mucosa, even when they show no symptoms(1). This no doubt will contribute to unwitting spread of the virus. The definitive causes of reactivation are not known. The frequency of asymptomatic shedding may be influenced by ethnicity (2) and, almost all patients with symptomatic primary HSV-2 infection had a recurrence within 15 months (3). This is irrespective of initial use of anti-viral agents. This present study on patients with recurrences was done to find out the situation in our locality, Middlesbrough, England where previous studies (4) have revealed a high prevalence of HSV infection.

Patients and Methods
A retrospective study of the casenotes of all patients diagnosed with primary genital herpes between January 1995 - December 1997 was done in January 2002. It was essential to have a record in the casenotes that the patient was diagnosed with a primary infection during the studied period. The genotype of the virus – (HSV-1 or HSV-2) must have been recorded. These patients constituted the cohort in the primary group. From the primary group, all those who re-attended the department because of at least one symptomatic recurrence were extracted and they formed the recurrence group.

Results
The computer generated 60 patients with this diagnosis for the study period. The case-notes of these patients were reviewed. Out of these, 56 patients (19 men and 37 women) fulfilled the criteria of primary infection with genital herpes. They constituted the primary group, 25 patients had HSV-1 and 31 patients had HSV-2. Analysis of the notes revealed that 16 patients (9 male and 7 females) re-attended the clinic with at least one symptomatic recurrence during the period of study. They constituted the recurrence group. In the recurrence group, the period between primary diagnosis and recurrence ranged from 4-32 weeks with a mean of 14 weeks (SD = 8.26 weeks). The viral genotypes in the recurrence group were HSV-2 in 14 patients and HSV-1 in 2 patients (table 1). Three patients (18.8%) in this group had six or more attacks in one year and needed antiviral suppression therapy. All the nine men had HSV-2 while five women had HSV-2, and two had HSV1 in the recurrence group. Among the recurrence group, one homosexual man was HIV positive and one woman suffered her first episode of recurrence at six months pregnancy. All the patients were Caucasians. There was no significant difference between the ages of those who recurred and those who did not, table 2.

Comments and Discussion
One of the difficulties in the management of herpes simplex virus infection is making a rapid accurate diagnosis. The number of patients in this cohort is smaller than the prevalence rate of HSV antibody positive patients in a previous study from this department (4). There is a need for a more rapid method of diagnosis and the PCR method is superior to tissue culture (5). The results within this cohort showed that HSV-1 was commonest among women in the primary group and HSV-2 was commonest among men with recurrences. The morbidity associated with HSV infection is physical and psychological. There is the fear of recurrent pain, the anxiety of spreading the virus to a sexual partner, informing a new partner of previous infection and disruption of social life. This often manifests as anger, depression and frustration (6,7). Some workers have suggested that people with recurrent episodes of HSV infection will have improved quality of life when given suppressive antiviral therapy (8). Despite efforts to control the spread of this infection, the incidence is increasing. The reasons for this include sexual activities during periods of asymptomatic viral shedding, and the fact that men with genital HSV-2 have more recurrences than women (3). In order to control the spread and decrease/prevent recurrences, more is needed than giving suppressive treatment. Initially it may be prudent to target patients with HSV-2 infection since they have higher rates of recurrences. Although some previous reports have suggested that the use homeopathic or complimentary medicines may be helpful, the results have been mixed and further studies are necessary (9,10). However some workers have claimed success in preventing or decreasing recurrence rates with the use of immune modulators like immiquimod(11), or resiquimod(12). These compounds when applied topically induce local production of interferon-alpha and interleukin- 2. The use of vaccines has also been found to be useful in decreasing recurrences. Research has shown that HSV-1 and HSV-2 induce specific CTL responses (13,14). Managing patients with HSV-2 infection with antiviral and vaccines will hopefully induce potent long lasting mucosal immune responses in the genital tract. In the study mentioned earlier (11), it was found that patients given an immune modulator like immiquimod alone or in combination with HSV vaccine had significantly reduced recurrences. Enhanced HSV specific immune responses correlated to the properties. In a report from the Czech republic, HSV sufferers were given levamisol and oral polio-vaccine, and follow-up results showed a significant decrease in recurrence (15).
This present study has shown that recurrences are more frequent in men, especially those that have genotype HSV-2. One way forward may be that at the time of initial diagnosis these patients are offered the opportunity to have vaccines and immune modulators in addition to anti-virals. This matter can be raised during counselling. However all patients diagnosed with HSV-2 infection should be offered this line of management. In so doing, it is hoped that the frequency of recurrences will be decreased. However, it is not clear whether this regime of antivirals, immune-modulators and vaccines will affect asymptomatic viral shedding.

References

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