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Efficacy of Viral Culture for HSV-2 Detection
Dear Dr.
In light of the high rate of false-negative results it produces, why is the viral culture still often regarded as the "gold standard" of herpes detection? Why would the increased specificity it affords outweigh the negative impact of such poor sensitivity? I am aware of the fact that it is less sensitive when taken after 48 hours and for recurrent outbreaks, but how sensitive is this test, on average, for swabs taken on first outbreaks within the first 48 hours of symptom presentation?
Roughly 45 hours after noticing what I feared were mild, atypical symptoms of a herpetic first outbreak, I had a viral culture performed; 7 days later, I was informed of the negative result. While the areas on my penis that were affected were slightly red and inflamed, there was no evidence of blisters, pain, or ooze. I understand that herpes cultures are most effective when there is ooze but that they can also detect the virus via the pickup of cells.
My question can be summed up succinctly: what are the differential rates of viral culture sensitivity depending on the nature of the sore, when it is taken, and whether its a first or recurrent outbreak? I read that it misses 70 percent of recurrent outbreaks and that the tests veracity drops dramatically after 48 hours of symptoms.
best,
O
In light of the high rate of false-negative results it produces, why is the viral culture still often regarded as the "gold standard" of herpes detection? Why would the increased specificity it affords outweigh the negative impact of such poor sensitivity? I am aware of the fact that it is less sensitive when taken after 48 hours and for recurrent outbreaks, but how sensitive is this test, on average, for swabs taken on first outbreaks within the first 48 hours of symptom presentation?
Roughly 45 hours after noticing what I feared were mild, atypical symptoms of a herpetic first outbreak, I had a viral culture performed; 7 days later, I was informed of the negative result. While the areas on my penis that were affected were slightly red and inflamed, there was no evidence of blisters, pain, or ooze. I understand that herpes cultures are most effective when there is ooze but that they can also detect the virus via the pickup of cells.
My question can be summed up succinctly: what are the differential rates of viral culture sensitivity depending on the nature of the sore, when it is taken, and whether its a first or recurrent outbreak? I read that it misses 70 percent of recurrent outbreaks and that the tests veracity drops dramatically after 48 hours of symptoms.
best,
O
excellent discussion on sensitivity vs specificity :)
grace
grace
Thank you for your help...I've read your previous posts and your credentials and trust your opinion.
--best.
O
--best.
O
MEDICAL PROFESSIONAL
From your description, plus 2 providers' opinions based on their examination, as far as I am concerned there already is "mathematical certainty" that your lesions weren't due to herpes. (Since 20% of the population has HSV-2, you certainly might be infected. But I am certain your penile "lesions" were not herpetic.) Perhaps this judgment might change if you had more definite evidence of exposure, for example if you are (or were) the regular (not one-time) sex partner of a person known to have HSV-2.
I doubt your doctors made a conscious decision to use culture rather than PCR. Most likely culture was the only test available to them. The HSV PCR test is not yet widely available outside major medical centers.
From your description, I see no need for delay in entering a new relationship nor an ethical need to inform your partners of possible herpes.
I doubt your doctors made a conscious decision to use culture rather than PCR. Most likely culture was the only test available to them. The HSV PCR test is not yet widely available outside major medical centers.
From your description, I see no need for delay in entering a new relationship nor an ethical need to inform your partners of possible herpes.
And I don't know if this helps, but the risky unprotected sex over a month ago only lasted 3 seconds because I immediately stopped after I realized how stupid I was.
Thank you for your reply. Part of the reason I feel I was not given a more sensitive test, such as the PCR, is because the doctor I saw felt that what he saw looked nothing like herpes (ie no vesicles blisters etc); they were just red blotches that faded out within 5 days. I really wish he would have though because my anxiety is pretty intense at this moment.
I saw two doctors who inspected my "lesions" and they both thought that they looked nothing like herpes, but I am still concerned because I desire mathematical certainty and it is a little bit too early for the blood test. I experienced these symptoms 49 days (7 wks) after exposure, but I read that people can fall outside of the normal range oftentimes with respect to the incubation period. I do not recall a prodrome, although I do remember having pressure marks on my glans for a few days beforehand that would disappear minutes after I took my jeans off. I had no pain, itch, or burning during urination during this period, although I think my urine was slighty darker than usual.
Do you think it is ethically mandatory for me to get the blood test before entering into a new relationship or do you think that the combination of information and the culture being negative is enough to feel safe. I will get the bloodtest anyway for my own peace of mind, but in your estimation, do you think there is good reason to assume it still may be atypical herpes?
I saw two doctors who inspected my "lesions" and they both thought that they looked nothing like herpes, but I am still concerned because I desire mathematical certainty and it is a little bit too early for the blood test. I experienced these symptoms 49 days (7 wks) after exposure, but I read that people can fall outside of the normal range oftentimes with respect to the incubation period. I do not recall a prodrome, although I do remember having pressure marks on my glans for a few days beforehand that would disappear minutes after I took my jeans off. I had no pain, itch, or burning during urination during this period, although I think my urine was slighty darker than usual.
Do you think it is ethically mandatory for me to get the blood test before entering into a new relationship or do you think that the combination of information and the culture being negative is enough to feel safe. I will get the bloodtest anyway for my own peace of mind, but in your estimation, do you think there is good reason to assume it still may be atypical herpes?
MEDICAL PROFESSIONAL
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
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
You are reading content posted in the STDs Forum
Herpes spreads by oral, vaginal and anal sex.
Herpes sores blister, then burst, scab and heal.
STIs are the most common cause of genital sores.
Millions of people are diagnosed with STDs in the U.S. each year.
STDs can't be transmitted by casual contact, like hugging or touching.
Syphilis is an STD that is transmitted by oral, genital and anal sex.
