Shedding of Herpes Simplex Virus
by Dr. H., Medical Director www.herpes.org
Earlier in the history of the understanding of herpes infections the medical and social management of the diseases caused by these viruses seemed easy: Patients were told to avoid having physical contact with possibly susceptible areas of other persons’ bodies when obvious symptoms were present, such as redness or blisters. Yet, a tremendous increase of persons now harboring herpes simplex virus in the genital area has occurred over the last twenty years. This vast growth in the numbers of herpes sufferers – now totaling over fifty million people in America alone – has not seemed to be readily explained by the much, much smaller number of persons who actually had obvious genital infections.
This information has caused scientists to examine how the virus spreads. The conclusions have been nothing short of astonishing.
About ten years ago in the Journal of the American Medical Association a landmark paper was published from the group at the University of Washington in Seattle which laid out for the first time the fact that patients with genital herpes “shed” virus from the genital tract, even when they don’t have any obvious symptoms. They found that overall in their study of 27 women, on 1% of days by virus culture these women shed herpes virus from the genital tract. They found that if the cultures were done daily for 100 days in these women, every single patient demonstrated shedding of virus at some time. Their conclusion was that women with genital herpes and their partners should be instructed regarding the possibility of asymptomatic shedding1.
This information was striking in its impact. It was equally slow to sink in to physicians caring for patients with genital herpes (or oral herpes for that matter). This low incidence of shedding on “only” 1% of days seemed to make the risk of being with someone with genital herpes who was actually shedding virus only 1 chance in a hundred. Those seemed like pretty good odds. The fact that every single patient was shedding virus at some time or other when symptoms were not present was lost in the hustle and bustle of medical practice.
It wasn’t until technology changed that the real facts of this situation began to emerge. Again in JAMA, and again out of Seattle, a paper emerged in 1994, which set the herpes world on its ear, where it has remained ever since.
Cone and others reported that out of 100 women in labor, all of whom had negative virus cultures for herpes, 6 had positive tests for herpes DNA in their genital tract. The test used was a new one called “PCR”, for polymerase chain reaction. From these women in labor, two babies were born that were infected with herpes simplex. Both of those mothers had negative cultures for the herpes virus, but both of them were excreting high levels of herpes DNA by the PCR test.
Interestingly, all patients who had positive viral cultures had positive PCR tests, as one might imagine. However, in the patients that had both positive viral cultures and positive PCR tests, the levels of DNA recovered were 250 times as high as in patients who had negative viral cultures.
Their conclusions were that if the mother’s Western blot blood test were positive, then the amount of exposure to the baby of herpes DNA was eight times higher and that the risk of exposure to the baby was higher as well2.
Armed with this new test, researchers began looking at populations of patients, both male and female, to determine what the scope of the shedding of virus from the genital tract really is and what it means to patients. The fact that viral cultures may be negative while at the same time the patient was producing viral DNA that could be detected in the genital tract clearly indicated that the nerve cells of the infected patients could be producing herpes virus at times when no symptoms were present. It also proved that viral cultures in the absence of any symptoms are extremely unreliable when compared to PCR testing.
Thus seemed to emerge two “stages” of a recurrence. The first stage could be said to be when the nerve cells were producing viral particles of any quantity, even small numbers of which were possibly being transmitted down the nerve fiber to the skin. The second stage could be said to be when sufficient viral particles were being transmitted along the nerve fiber back to the skin to actually produce an inflammatory response showing up as redness, swelling, “papules”, and ultimately blister formation3. It took Wald’s historic publication in 1997, however, to crystallize the true nature of this condition and set it out for what the impact truly might be on the human population.
Wald, Corey, and Cone studied 27 women with positive blood tests for genital herpes. They found that 28% of the patients over about two months had positive PCR tests for genital herpes (taken from their genital tract), though only 8% had positive herpes cultures4. This is similar to the results mentioned above.
However, they found that 2 of the patients were excreting herpes DNA ON MORE THAN 75% OF THE DAYS IN WHICH THEY WERE TESTED! This result was nothing short of astonishing, as these were patients that were not having symptoms. The point was clear: Some patients with genital herpes – about 10% in this study – excreted virus most of the time from their genital tracts.
Wald et al brought with this new knowledge, though, one of the first rays of hope. They further studied these patients in a double-blind study using acyclovir given to the patients to see if herpes DNA excretion as determined by PCR was diminished by acyclovir. This was important because, as Wald pointed out, the enzymes that are acted upon by acyclovir “are made relatively late in the viral replication cycle…”. She pointed out that “in vivo inhibition of PCR positivity by acyclovir would indicate the presence of replicating and hence potentially infectious virus on mucosal surfaces4.” In other words, if herpes DNA was decreased at the skin by use of acyclovir, then positive PCR tests mean that the patient is probably contagious.
The study found that acyclovir did make herpes DNA go away, as documented by PCR tests. In fact they found that HSV DNA rapidly disappeared from mucosal surfaces when acyclovir was taken in dosages of 400 mg twice daily. To quote Wald, “the median reduction in shedding during acyclovir therapy was 100% by viral isolation (editor – meaning viral culture) compared with 80% by PCR assay4.” This means that the amount of reduction of detectable virus was 80% when acyclovir was taken by patients who had been shedding virus. This fact brought new hope to herpes sufferers worldwide, and thus it also opened the flood gates for new areas of herpes research.
A recent study has shown that it is possible to actually let the herpes sufferers take an antiviral chemical which will make them less contagious. Since it is known that acyclovir decreases detection of viral DNA, it turns out that it also makes patients less contagious! This has been a revolution in the management of couples in which one partner is infected and one partner is NOT infected. See the Medical Advisory Board’s statement on this important landmark study.
What is the take-home message on the concept of shedding of herpes simplex from the genital tract? Patients with genital herpes must remember that they may be shedding virus and not be aware of it. Further publications have indicated that many patients don’t pay attention to very slight symptoms that, in fact, means that they are having mild outbreaks5. Good education of patients may help them to recognize subtle symptoms.
Patients should also have hope that through modification of life style, using appropriate precautions, and through the use of non-prescription products and/or prescription medication, they can achieve a high level of control of genital herpes and drastically decrease the likelihood of transmitting the infection to a loved one.
1 Frequency of asymptomatic shedding of herpes simplex virus in women with genital herpes, Brock BV, Selke S, Benedetti J, Douglas JM Jr, Corey L, “JAMA 1990 Jan 19;263(3):418-20, Department of Laboratory Medicine, University of Washington, Seattle.
2 Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women,Cone RW, Hobson AC, Brown Z, Ashley R, Berry S, Winter C, Corey L, “JAMA 1994 Sep 14;272(10):792-6″, Department of Laboratory Medicine, University of Washington, Seattle.
3 Personal Communication, Raymond L. Fowler, M.D., FACEP, Oct 2000
4 Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment, Wald A, Corey L, Cone R, Hobson A, Davis G, Zeh J, “J Clin Invest 1997 Mar 1;99(5):1092-7″, Department of Medicine, University of Washington, Seattle 98195, USA.
5 Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons, Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, Krieger JN, Corey L, “N Engl J Med 2000 Mar 23;342(12):844-50″, Department of Medicine, University of Washington, Seattle 98122, USA.
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