Subclinical Shedding Research Articles

Herpes simplex virus shedding among human immunodeficiency virus-negative men who have sex with men: site and frequency of shedding.

The frequency and anatomic location of subclinical and symptomatic herpes simplex virus (HSV) shedding were evaluated among human immunodeficiency virus (HIV)-negative HSV-2-seropositive men who have sex with men (MSM). Eight men attended a research clinic daily for 30 days for a detailed genital examination and anoscopy with colposcopy to detect herpes lesions. HSV cultures were obtained daily from four sites (perianal, urethral, penile shaft, and oral) at home and the research clinic. Signs and symptoms of genital herpes were recorded by the participants and clinician. Three (37.5%) of the men shed HSV. Overall, the 8 men shed HSV on 5.5% of days cultures were obtained and shed subclinically on 2.7% of days. All HSV shedding was perianal or rectal; only 1 symptomatic recurrence, concurrent with an external perianal lesion, was detected by anoscopy. Subclinical HSV shedding was frequent among HIV-negative MSM, and anoscopy with colposcopy did not increase the detection rate of rectal HSV lesions or shedding.

HERPES SIMPLEX VIRUS–2 INFECTION: An Emerging Disease?

Genital herpes infections continue to increase in the world. As outlined previously, several factors play a role in the continued transmission of genital herpes worldwide. Reducing the medical consequences of HSV-2 infection will not be easy. It is also sobering to realize that widespread penetration of HSV-2 into the population had preceded the spread of sexually acquired HIV in most countries. The biological rationale for a connection between HIV and HSV continues to be strengthened. Currently, a specific program to decrease the transmission of genital herpes does not exist. Recent studies with antiviral agents indicate the potential of these compounds to reduce shedding in HIV-negative and in HIV-positive persons and potentially may be useful in preventing some aspects of HSV transmission. Advances in laboratory techniques to assist in the diagnosis of genital herpes infections have added to our knowledge of the natural history and epidemiology of infection. Because of imperfect laboratory tests, negative results do not always indicate lack of infection; this has important public health implications. Large numbers of unrecognized symptomatic cases and frequent asymptomatic shedding are the likely source of continued genital HSV-2 transmission. Solutions for reducing the transmission of genital herpes range from simple, such as counseling patients regarding symptoms and signs of genital herpes and the frequency of subclinical shedding, to complex and expensive, such as screening high risk populations (e.g., STD clinic attendees) for HSV-2 infection. Chronic antiviral therapy may be indicated in HSV-2 seropositive persons without monogamous relationships as they are at risk to transmit HSV to multiple persons. The authors' aim in this review is to provoke discussion of such a control program and to raise the consciousness of the feasibility of instituting control measures for selected populations. We hope to elicit pilot programs designed to reduce the morbidity of this old but re-emerging infectious disease.

Subclinical herpes virus reactivation and latency

Although there has been considerable refinement in our understanding of the processes underlying the establishment and maintenance of latency, important research questions remain. Results from various workers imply that the establishment of latency may be a dynamic process and may offer possible therapeutic targets. The role played by the latency-associated transcripts appear to be important in both establishing latency and in aiding reactivation. Recent work has shown that reactivation in vivo is much more frequent than previously thought and leads principally to subclinical viral shedding. Factors influencing subclinical shedding for most patient groups and the response and limitation of therapy have been clearly determined.

Genital herpes

Genital herpes is a common viral infection in the developed and developing world. Recent studies of the natural history of genital herpes infection confirm that recurrence rates may be high and subclinical shedding is common in persons with herpes simplex virus type 2 infection. These results have important implications in some areas of clinical medicine such as the prevention of neonatal herpes, where confusion is still common. Although numerous treatment options continue to be explored, conventional antiviral drugs remain the mainstay of therapy, and in the area of herpes vaccine development the viral subunit vaccines continue to show the most promise for the control of genital herpes infection.

Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir: Wald A, Zeh J, Barnum G, et al. Ann Intern Med 1996;124:8–15

Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir: Wald A, Zeh J, Barnum G, et al. Ann Intern Med 1996;124:8–15

Asymptomatic maternal shedding of herpes simplex virus at the onset of labor: Relationship to preterm labor

To determine if fetal growth restriction and prematurity are observed with subclinical shedding of herpes simplex virus (HSV) at the onset of labor. Within 48 hours of delivery, cultures were taken from the cervix and external genitalia of 15,923 asymptomatic pregnant women without symptoms or signs of genital HSV infection; results were positive for HSV in 57. Each of these 57 women were compared with a control group composed of the three culture-negative women delivering immediately before and the three delivering immediately after each woman shedding HSV. The median birth weight for infants born to the 57 women with asymptomatic shedding was 3050 g, compared with 3360 g among the 342 women without asymptomatic shedding, a statistically significant difference (P < .002). These differences were due to very low birth weight (LBW) among the five infants of women with subclinical viral shedding secondary to recently acquired primary genital herpes; these five infants had a median gestational age of 33 weeks, compared with 37 weeks for the 14 infants of mothers with nonprimary, first-episode disease and 39 weeks for the 33 infants of women with reactivation disease, also a significant difference (P = .018). Asymptomatic genital shedding of HSV at the onset of labor because of subclinical primary genital HSV infection is associated with preterm delivery. Women who acquire genital HSV-2 before pregnancy and are shedding subclinically at the onset of labor experience no increase in adverse outcome. Thus, prevention of the prematurity and LBW associated with genital herpes means that acquisition of the infection in late pregnancy must be prevented.

Acyclovir Cuts Down on Subclinical Shedding in Herpes

Acyclovir Cuts Down on Subclinical Shedding in Herpes

Oral aciclovir suppresses subclinical shedding of HSV-2

Oral aciclovir suppresses subclinical shedding of HSV-2

Acyclovir suppresses subclinical shedding of HSV-2 in the genital tract

Acyclovir suppresses subclinical shedding of HSV-2 in the genital tract

Virologic characteristics of subclinical and symptomatic genital herpes infections.

The frequency, pattern, and anatomical sites of subclinical shedding of herpes simplex virus (HSV) in the genital tract, along with factors that predict such shedding, have not been well characterized. We studied prospectively the clinical and virologic course of genital herpes in 110 women. The women kept symptom diaries and provided daily samples from the vulva, cervix, and rectum for viral culture. During a median follow-up of 105 days, subclinical shedding of virus was identified in 36 of 65 women (55 percent) with HSV type 2 (HSV-2), in 16 of 31 women (52 percent) with HSV type 1 (HSV-1) and HSV-2, and in 4 of 14 women (29 percent) with only HSV-1. Among women with genital HSV-2 infection, subclinical shedding occurred on a mean of 2 percent of the days. The mean duration of viral shedding during subclinical episodes was 1.5 days, as compared with 1.8 days during symptomatic episodes. HSV was isolated from several sites in the genital tract and rectum in 17 percent of subclinical episodes and 22 percent of symptomatic episodes. Half the episodes of subclinical shedding of HSV occurred within seven days of a symptomatic recurrence. The risk of subclinical shedding increased with the frequency of symptomatic recurrences. Subclinical shedding was more frequent among women with more than 12 recurrences per year than among those with no symptomatic recurrences (odds ratio, 3.3; 95 percent confidence interval, 1.4 to 7.9); it was also more frequent among women who had recently acquired genital herpes (odds ratio for women with HSV acquired in the past year as compared with those who had had the infection for a year or more, 1.85; 95 percent confidence interval, 1.1 to 3.1). Among women with a history of genital herpes infection, subclinical shedding of HSV is common and accounts for nearly one third of the total days of reactivation of HSV infection in the genital tract. Women with frequent symptomatic recurrences also have frequent subclinical shedding and may be at high risk for transmitting HSV.