I know this sounds rather startling (but it does get your attention): Most of us have probably or will have a herpes simplex infection. There are two major herpes simplex viruses: herpes simplex 1 (HSV-1) and herpes simplex 2 (HSV-2). Although HSV-1 is the “one” that commonly causes the cold sores we get on our lips and mouth, especially when our immune guard is down, it can also cause genital disease. Herpes 2 is the more “classic” cause of genital herpes. (For more complete information on herpes see my article “Shedding the Herpes Virus: Even when you don’t know you have it” archived on my website judithreichman.net.)

Many of us have had our first bout of HSV-1 in childhood (and developed cold sores), but epidemiologists are now finding that more and more HSV-1 infections occur later in life, causing genital disease in young adults. The type of herpes that is present “up there”, or “down there” can be differentiated through a blood test for specific type 1 or type 2 antibodies. (The test is aptly termed Herpes Select.) However, most HSV infections occur without symptoms and only 10 to 20% of persons with antibodies to HSV-2 have recurrent disease. That’s why HSV is so easily spread, the virus can be shed without a lesion, is highly contagious and voila, sexual contact allows it to pass to and infect a partner.

As usual I spent part of my weekend perusing medical journals. The most interesting articles (for me) are often found in general medical journals, and sure enough there was one that appeared in the January 5th JAMA titled “Efficacy Results of a Trial of Herpes Simplex Vaccine”

There was a time before we became so concerned about the spread of HIV and HPV, when patient and doctor concerns were focused on herpes. The question commonly posed to gynecologists was “if we can put a man on the moon, why can’t we develop a herpes vaccine?” And we, the ObGyn’s would sadly bow our heads and admit research failure. Well the researchers are still working on developing that vaccine… The study reported in this article was supported by the National Institute of Allergy and Infectious Diseases and the pharmaceutical company GlaxoSmithKline. (Guess why the latter corporation is interested.)

The study of the efficacy of the herpes vaccine that they had tried to develop was appropriately performed. It was randomized, double-blinded and included 8323 women ages 18 to 30 that were negative for antibodies for HSV-1 and HSV-2. These women were divided into 2 groups and either received the investigational herpes vaccine at months 0, 1 and 6 or a control vaccine (which was an inactivated hepatitis A vaccine) on those 3 occasions. The women were then followed for development of HSV-1 or HSV-2 from one month after the second dose through month 20.

Although the study doesn’t seem that huge, it was…it was carried out at 50 clinical sites in the United States and Canada: 31,770 women were screened for antibodies to HSV-1 and HSV-2 and 12,468 were negative. From the latter group, 8323 women met eligibility criteria (I guess they agreed to take the three injections and could be appropriately followed) and were then enrolled.

The researchers found that, overall; the vaccine was 55% effective against HSV-1 infection but was not effective against HSV-2 infections even though it produced antibodies against HSV-2. They weren’t sure why. Rather than admit defeat (at least a type 2 defeat) the authors proposed the following: “Among the control subjects in the present study, 60% of the cases of genital disease and two thirds of the infections were caused by HSV-!….HSV-1 now rivals HSV-2 as a cause of neonatal herpes disease….and although the development of a vaccine that provides protection against HSV-1 genital disease is a substantial step forward, additional progress is needed before a herpes vaccine is likely to be approved for general use.”

In other words, we still don’t have that vaccine against herpes…even though we have put a man on the moon.

I’m currently at 39,000 feet on my way to NY to have a fun weekend with my daughter. I slipped a few medical journals into my carry-on to review so that I could find an article to share in my weekly newsletter. The seat is cramped, the cabin is crowded, most of my fellow passengers are sleeping….I passed over articles on multiple therapies for tuberculosis (too much coughing going on around me), sepsis and organ failure, as well as AIDs – defining cancers (too depressing)…Each subject is critical to the progress of medicine and I did read up on them, but for this newsletter I selected an article in JAMA titled ” Genital Shedding of Herpes Simplex Among Symptomatic and Asymptomatic Persons with HSV-2 Infection”.
So here it is…answering the question: do individuals who don’t know they have genital herpes shed the virus (and hence can spread it to a partner) to the same extent as those that have recurrent lesions (and are aware of their diagnosis)?

A quick herpes review: Genital herpes (HSV-2) is unfortunately, extremely prevalent. Over half a billion people worldwide have the virus and it is estimated that 23.6 million persons aged 15 to 49 become infected annually. In the US, 16% of adults have had it as evidenced by the fact that they have antibodies to HSV-2, but only 10 to 25 % of persons with this “everlasting infection” know that they harbor it. As a result, individuals who don’t know they have had herpes spread most of the HSV-2 infections. The risk of sexual transmission doesn’t correlate with recognition of symptoms but is correlated with silent viral mucosal shedding (and obviously, sexual contact with a partner).

Researchers at the University of Washington enrolled participants who were 18 and older in this herpes study for the published study. They advertised for participants through word of mouth at the university, newspaper ads (and promises of payment), tested many and in the end found 498 individuals who had antibodies to herpes 2. They then divided them into 2 groups: those who were symptomatic (had a clinical history of genital herpes) and those who were not (never knew that they had a lesion, their diagnosis was made with the herpes antibody blood test). Each person then self-collected swabs of their genital secretions for at least 30 days. (The swabs were examined by quantitative polymerase chain reaction for HSV DNA…I had to add that for the purists.)

The results showed that those who had symptomatic genital lesions were twice as likely to shed the virus and 3 times more likely to develop lesions than those who were, on initial testing, asymptomatic. However in those with no symptoms, genital HSV shedding did occur on 10% of days, and almost all of it was subclinical (i.e. the person did not recognize a lesion). There was a similar shedding rate between men and women; which means that men can have sub-clinical shedding on normal appearing genital skin. (There goes the adage, look before you engage…)
What they also found was that many of those who were initially asymptomatic begin to recognize recurrent herpes once they had received the diagnosis through their blood tests. They may have felt that what they had in the past was just a mild irritation or itch and ignored it, now they didn’t.

I have frequently been the doctor who sees a patient with “something down there” and either through direct culture and/or a blood test have made the diagnosis of herpes. Often the first statement posed by my now horrified patient is “he never told me”, or “was he with someone else?” Neither may be correct…the partner may not have known that he (or she) had acquired herpes in the past, or the woman with the “new” herpes infection may have had it all along and only now has become aware of a clinical lesion. (Perhaps brought on by illness, stress or diminished immunity.)

It certainly would be helpful to have universal herpes 2- antibody testing. But this is not currently a part of “routine” blood tests, nor is it financially feasible. The best protection will continue to be the use of condoms. For those who have been diagnosed with herpes, daily prophylactic use of the antiviral medications such as Valtrex or acyclovir should decrease shedding as well as recurrent lesions. So far that’s the best advice that’s offered by the experts. Somewhat depressing at 39,000 feet (or for that matter at sea level)!