Good questions. However, you start with a misconception; i.e., the premise that culture is the "gold standard" for herpes diagnosis is not correct. Culture is a gold standard only if positive. If there is any doubt about the diagnosis in a particular patient, a positive culture can settle the issue once and for all. However, as you correctly state, culture is often negative in HSV infected people, even those with typical genital lesions.
To use epidemiologic terminology, this means that culture is a highly specific test. However, continuing to use that terminology, culture is a very insensitive test; that is, it often is negative in a person with herpes. As you might imagine, in people without genital lesions, the culture almost always is negative, even in people with herpes.
Bottom line: If a gold standard test is one that is both highly sensitive (missing few infections) and highly specific (always reliable if positive), then culture does not meet that standard. But nobody ever said it does -- so I'm not sure why you apparently thought of it that way.
As to the specific questions you ask, there are no better answers than the ones you provide yourself: culture indeed can miss many (most?) initial herpes; and with recurrent outbreaks they often miss the diagnosis if done more than 48 hours after onset. Clearly the culture is most likely to be positive when used to test fresh herpetic vesicles (blisters); less likely as the blisters become pus-filled; still less as they open into sores; and rarely positive in those whose lesions are starting to heal. For initial genital herpes, new lesions often continue to appear for 1-2 weeks, so the culture may be positive for that long. For recurrent outbreaks, the vesicle-pustule stage usually is over within 2-3 days. (Forty to fifty percent of apparently initial infections actually are recurrent outbreaks in people with previously asymptomatic infection. This lowers the positive culture yield for apparent first outbreaks, if tested beyond a couple of days. So your 70% figure might be abour right.)
With increasing use of polymerase chain reaction (PCR) instead of culture, false negative results are less common. But even PCR misses many cases, especially when lesions are not present (of course) and when they are healing.
It is for exactly these reasons that culture (or PCR) alone is inadequate as a diagnostic tool. Proper diagnosis requires culture/PCR sometimes, blood tests sometimes, and often both. This is not unique to herpes. For 100 years, syphilis diagnosis has been essentially the same: a specific but insensitive test to identify the organism itself (darkfield microscopy) plus blood testing, with the two approaches often used simultaneously. There are parallels in the diagnosis of most infectious diseases.
Good questions. Thanks for the opportunity to discuss it.
HHH, MD .
