A Prospective Study of New Infections with Herpes Simplex Virus Type 1 and Type 2
abstract & commentary
Synopsis: Nearly half of all newly acquired HSV-2 infections are asymptomatic. Asymptomatic infections are more common in men than in women.
Source: Langenberg AG, et al. N Engl J Med 1999;341: 1432-1438.
This project was initially developed to study the effectiveness of a vaccine for the prevention of herpes simplex virus (HSV) infection. The trial vaccine was found to be ineffective. However, Langenberg and colleagues determined that the participants were appropriate for a prospective study of infection with HSV types 1 and 2. The enrolled 2393 individuals who were seronegative for HSV-2, though 63% of the cohort had antibodies to HSV-1. Most of the study participants were identified at STD treatment centers and had four or more sexual partners in the year prior to enrollment. Twenty-two percent were individuals who were in an exclusive sexual relationship with a partner with a history of HSV-2.
An individual was considered to have acquired an HSV infection if HSV seroconversion occurred, a culture was positive for HSV, or both conditions occurred. The period of follow-up was short, averaging only 15 months. The demographic characteristics of those participants who acquired an HSV infection did not differ from those who did not seroconvert. During the follow-up period, 155 cases of HSV-2 and 19 cases of HSV-1 (new, primary infections) occurred. The overall rate of acquisition of HSV-2 was 5.1 cases per 100 person-years and was higher for women (6.8 per 100 person-years) than for men (4.4 per 100 person-years). Only 31% of the documented infections in men were symptomatic compared to 44% of the cases among women. The presence of antibodies to HSV-1 at study entry did not protect against the acquisition of HSV-2. However, individuals who acquired an HSV-2 infection who were HSV-1 seropositive at entry were much more likely to have an asymptomatic initial HSV-2 infection.
A total of 55 of the 155 seroconverters appeared for examination in one of the clinics because of genital lesions or other symptoms consistent with HSV infections. An additional 3% of the seroconverters gave a history of typical primary herpes virus infection but did not appear for examination. Eventually, 79% of the individuals who had symptoms of genital HSV infection were found to have a positive HSV-2 culture, though not all cultures were positive at the time of the first examination. Seven individuals with documented HSV-2 conversion had symptoms that were not typical. These symptoms included meningitis, cystitis, dysuria, lumbar radicular pain, urethritis, penile dermititis, and pubic falliculitis.
Overall, only 37% of patients who had HSV-2 seroconversion had a clinical diagnosis of genital herpes during the course of the trial.
Nineteen individuals developed a primary HSV-1 infection during the trial. Thirty-two percent of these had genital lesions associated with their serocoversion. The virus was isolated from five of the six patients with genital lesions.
Despite the fact that these trials were carried out at centers where the professional personnel were thoroughly familiar with the signs and symptoms of genital herpes, there were a few cases of misdiagnosis. Serologic assays proved to be more accurate than cultures for the detection of new cases of HSV infection.
COMMENT by Kenneth L. Noller, MD
This prospective trial contains information that is important for all of us who care for both women and men with HSV genital infections. It is clear that asymptomatic HSV-2 genital infections occur with some frequency. It is also clear, if a person has HSV-1 antibodies and acquires an HSV-2 infection, he or she is considerably more likely to have an asymptomatic infection than an individual who did not have the protection of the HSV-1 antibodies.
I was surprised to see the large difference in the occurrence of asymptomatic infections between men and women. Because HSV infections of the vagina tend to be asymptomatic, I assumed that more women would have asymptomatic infections than men. The contrary was true. Most of us who do a lot of colposcopy have seen vaginal HSV infections in women who have no clinical history of having had HSV.
While this is a good study that is well-written and easy to read, I do have one criticism of the conclusions reached by Langenberg et al. They state in the first sentence of their discussion that, "This prospective study defines the natural history of newly acquired symptomatic and asymptomatic HSV infection in sexually active adults." Because their study population is not representative of the general population of sexually active adults, they should have modified their statement by adding the phrase "attending an STD treatment clinic." There may be considerable differences in the rates of acquisition of the disease and the occurrence of symptomatic infections in the general population of sexually active adults.
In the article by Langenberg et.al. which of the following statements was found to be true?
a. HSV-1 antibodies protect against the acquisition of HSV-2 genital infections.
b. Attendees at STD clinics are more likely to acquire asymptomatic HSV infections than the general population.
c. Genital HSV infections are more likely to be symptomatic in females.
d. HSV-2 cultures were the best method for determining the occurrence of a new HSV infection.
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