Westover Heights Clinic - Diagnosing Genital Herpes

    Genital herpes can be challenging to diagnose, but an accurate diagnosis is the cornerstone for everything that follows and is absolutely essential.  Proper diagnosis cannot be stressed strongly enough.  Methods are changing rapidly, so be prepared for some ambiguity and misinformation about the process.  But don't settle for anything less than conclusive.  You don't have to, and you'll be glad that you persevered in getting the best possible answers.

    There are three ways in which the diagnosis of herpes can be made.  They include a physical examination, swab tests, and/or a blood test.  With all three techniques, a carefully gathered medical and sexual history adds to accuracy.

Physical Examination
    A physical exam is one of the most frequently used (and least reliable) diagnostic methods.  A physician, nurse practitioner, physician's assistant or RN trained in STD evaluation usually does the exam. First, the examiner completes a verbal health history related to the course of the illness.  They will need to know what sexual practices the patient participates in (oral sex, vaginal intercourse, anal sex) in order to know which areas to check for symptoms.  This may feel awkward to patients, but it is useful to remember that people who work in the medical field are virtually unshockable.  It is essential that all information requested be provided as honestly and completely as possible.

    Next, they look for symptoms associated with genital herpes.  For women, this may include a pelvic examination of the internal reproductive organs.  If there are painful lesions, the clinician may elect to eliminate the internal part of the exam until symptoms subside.  During a typical female exam, the external genitalia, vagina, and cervix will be inspected for lesions and unusual discharge. In men, the penis and scrotum will be examined for sores.

    Both men and women will also be checked for signs of infection in or around the rectum, on the thighs and buttocks, in the pubic hair area, and in and around the mouth. Lymph nodes in the groin will be checked for enlargement and tenderness. If lesions are not present, a physical exam will not provide an accurate diagnosis, to diagnose or rule out herpes infection. The advice of the U.S. government's CDC (Centers for Disease Control) is that laboratory tests be done to confirm the opinion of the clinician.  Studies have shown that clinicians, based on a clinical exam alone, incorrectly identify things as herpes that are not really herpes up to 20% of the time.  Insist on lab testing in addition to an exam.

SWAB TESTS

Viral Culture
    For a viral culture, a swab is rubbed vigorously across an area of skin that looks abnormal.   The material that is gathered on the swab is put into a liquid before sending the specimen to the laboratory.  The swab should be made of a synthetic material, like Dacron or polyester never cotton, and the shaft of the swab should be plastic, never wood.  It may be necessary to gently open a lesion to recover enough material to get a good sample.  The container with the liquid and the swab tip inside is sent to a laboratory. There, healthy animal cells are combined with the patient sample. A laboratory technician then observes the culture for changes that typically appear when herpes is present. If such changes occur, the test is declared positive, meaning that the herpes virus is present in the sample.  Typing should then be done on the sample to see if the patient has HSV 1 or 2.  If the changes do not occur, then the sample is declared negative, which means there was insufficient virus or no virus present in the sample.

    A negative result does not necessarily mean that the person does not have herpes.  If the test is negative, it could be because the sample was gathered too late in the outbreak, that the culture was handled inappropriately in the medical office or at the lab, or that it took too long for the sample to get to the lab before processing.  One study found that herpes cultures give FALSE NEGATIVE results 76% of the time when compared to the more accurate PCR test described below.  That means that 76% of the time when a culture comes back negative, the person really does have herpes after all, when compared to the same sample run by PCR.   

    All negative cultures should be followed up with an accurate blood test three to four months from possible exposure to see if the person really has herpes.  False positive cultures are extremely rare. If a culture is positive, a person can safely assume that they do have herpes.  The traditional culture can take 7 to 14 days to grow. There are new tests on the market that give faster results, some as quickly as 18 hours.  These may be slightly less sensitive than cultures that grow the full 7 to 14 days.

PCR (Polymerase Chain Reaction)
    The PCR swab test is also performed by gathering a sample from an abnormal area of skin.  However, this test is much more sensitive than a culture meaning more true cases of herpes are picked up when using this test.  Simply put, the PCR test takes a tiny sample of the virus and amplifies it many times so it can be seen and subsequently typed.  

    This test is now available routinely in large national labs but may be more expensive than culture for the self-paying patient.  Smaller local labs may not yet be using HSV PCR.  It is, however, four times more sensitive than a culture and should be used whenever possible for diagnosing herpes from a swab sample.  

    In addition, samples tested by PCR instead of culture are much more stable and less likely to be influenced by transport issues or by the length of time it takes to get samples to the lab.  In the future, culture will likely be replaced completely.  Only PCR should be used to test and type spinal fluid and babies with suspected herpes infections.

Tzanck Preparation
    The Tzanck test is sometimes used in sexually transmitted disease (STD) clinics for a quick diagnosis, or it may be used for a quick, initial diagnosis while the culture or PCR is being run.  For this test, cells from the base of a lesion are collected on a swab, placed on a glass slide, stained with a special stain, and examined under a microscope.  Cells infected with herpes virus show up as very large with many centers (also knows as multinucleated giant cells).  Infected cells pick up the stain in a different way than uninfected cells. This test is definitely not as desirable as a culture or PCR, but a positive Tzanck, read by an experienced lab person, combined with a good physical exam, sexual history and the presence of symptoms consistent with herpes infection is reasonably accurate.

    However, a negative Tzanck is not at all definitive. As with cultures, if a negative result is obtained, it should be followed in three to four months from possible exposure with an accurate blood test to determine if herpes infection has actually occurred.  Also, Tzanck stains cannot separate HSV 1 from HSV 2, which is an essential part of diagnosis.

Pap Smear
    A Pap smear is a process similar to the Tzanck test, but a different staining technique is used. However, Pap smears tend to be available in more laboratories than Tzanck preparations.

    There is a new test sometimes called a "Silver Pap" that has shown up in a few laboratories.  With this test, a herpes PCR is included in a pap smear along with gonorrhea and chlamydia testing.  It is important to understand what is happening with this test that is looking to see if herpes virus is present at the time the Pap smear is taken.  If the test is negative for herpes, it does not mean the person is not infected.  It simply means that there was no virus present at the time the sample was gathered.  Unlike gonorrhea or chlamydia, herpes virus isn't always present on the cervix of an infected person.  There can certainly be confusion about the meaning of a negative "silver pap".  The only way to know about herpes infection in a person not experiencing symptoms (who is asymptomatic) is to look for the antibody to the virus in a blood test, not for the virus itself.

BLOOD TESTS
    The most encouraging aspect of diagnosis right now involves the emergence of new, type-specific blood tests for herpes.  Herpes blood tests look for the antibody to the herpes virus, and a positive antibody test means that the person is definitely infected with herpes and is infectious to others.  There is no such thing as a blood test being positive because of "exposure."  It's similar to being pregnant - you are or you are not, there is nothing in between.  Antibody is a protein made by our bodies in response to a virus, and sometimes it can take a while for an individual to develop it.  That's why it is important to wait long enough from infection until testing to make sure the test is accurate.  The ideal time is three to four months from the possible infecting episode to testing.

 
    Old-style blood tests (called crude antigen tests) could detect antibody to herpes simplex in general but were very poor at differentiating accurately between types 1 and 2.  So if a person had either cold sore virus or genital herpes virus, the blood test would be positive for herpes antibody. These old style tests are not reliable because they imply that they can tell the difference between HSV 1 and 2 but really cannot. So a person could be told they had HSV 2 (which is almost always genital herpes) when really they had HSV 1 (still most often the cold sore virus).  This inability to distinguish between the two viruses is called cross reactivity.

    The new tests, called type-specific serologic tests (or TSST), do distinguish between HSV 1 and 2 with a high degree of certainty. The new accurate tests all measure a kind of antibody called IgG.  They are based on the detection of glycoprotein G, a substance specific to HSV 1 or HSV 2.  TSST do not mistakenly detect antibody from other herpes viruses such as chicken pox.  

    A type-specific IgG blood test may also help sort out a new from an old infection.  Let's say someone develops a lesion in the genital area.  A swab test is taken, either culture or PCR, and the result shows HSV 2 detected.  At the same visit, a blood sample is drawn.  The TSST test is negative for HSV 2.  This would indicate that this is a first infection because virus is present but not enough time has passed for antibody to the virus to be made by the body.  So the combination of a positive swab test and a negative antibody blood test for the same type means the person has a first infection with that herpes simplex virus.    IgM (a different kind of antibody than IgG) tests do not accurately distinguish between the types of virus (HSV 1 and HSV 2) nor can they accurately tell a new infection from an old one.  IgM tests may also erroneously pick up other herpes viruses like chicken pox or mono virus.  IgM tests for herpes should be avoided completely.    

    So, who should have blood tests for herpes anyway?  This is still somewhat controversial, but here is a partial list of those who might be good candidates for a herpes blood test:

1.  Anyone who has had a sexual partner in the past and wonders if they may have gotten herpes without developing symptoms.

2.  Someone who has been diagnosed with herpes by a visual exam alone and either wants confirmation of the diagnosis or to have his or her virus typed.

3.  Someone who has had repeated or a single negative herpes culture from skin lesions that were suspected to be herpes by the examining clinician.  Since herpes cultures and even PCR swabs can be falsely negative, a blood test should be used as a follow up test when sufficient time for seroconversion (going from a negative blood test to a positive blood test.)

4.  Someone who has had symptoms diagnosed as recurring urinary tract or bladder infections but never grows out bacteria on a urine culture.  Instead of an infection in the bladder, they may have herpes lesions in the urethra (herpetic urethritis).  Urine hurts while passing over these open lesions in the urethra because urine is acidic, and there are white cells on a urine dip test because these herpes lesions produce white cells so these white cells are picked up by the urine as it leaves the body.  

5.  Anyone who wants to get screened for sexually transmitted diseases.  Typical STD screens do not include a herpes test.  You need to ask if herpes testing is included and, if not, request that it be added to the STD screen.  Herpes is the most prevalent STD in the US today. Chlamydia and genital warts are more incident infections - that is there are more new cases of those in a year than new cases of herpes.  But because most people eventually get treated for chlamydia and most people clear genital wart virus within 12-24 months after acquiring it and no one clears HSV 2 infection, HSV 2 is the more prevalent STD in the US today.

6.  Pregnant women who want to know if they are infected or still vulnerable to genital HSV infection.

There are now five type-specific, glycoprotein G based, serologic tests available:

Western Blot
    The oldest test, the Western Blot, was developed at the University of Washington by Dr. Rhoda Ashley Morrow, and, in the U.S., is still done only at that facility.  It is very accurate.  Samples can be sent to the University of Washington laboratory from any place in the United States.  For more information, call 206-598-6066.

HerpeSelect
    The second and third tests, the HerpeSelect IgG for Herpes Simplex 1 and 2, are produced by Focus Diagnostics. HerpeSelect has two test formats: The EIA (or ELISA) and the Immunoblot.  They are both glycoprotein G based tests, accurately distinguish between HSV 1 and 2, and are very sensitive and specific for herpes.  The HerpeSelect is the test a clinician would optimally get when sending blood to a national reference lab and requesting a type-specific serology.  The following are test codes that should be used when ordering these tests at the two large national laboratories.  We're unable to know or list the codes for smaller community laboratories.

Quest Diagnostics
HerpeSelect HSV-2 ELISA: 3640x            
HerpeSelect HSV-1 ELISA: 3636x
Both HSV-1 and HSV-2 (but separately): 6447x        
Confirmation of HSV 2 by inhibition assay:  17170X

LabCorp
    HSV-2 ELISA: 163147                    
    HSV-1 ELISA: 16489
    Both HSV-1 and HSV-2 (but separately): 164905

Biokit
    The Biokit test looks for antibody to HSV 2 only and is an in-office test.  Blood is collected using a finger prick, and the test takes about five minutes to run.  It must be performed in a laboratory that has been nationally certified, but most clinician's offices are not.

Captia
    The Captia test is also done in the ELISA format, but in some studies was found to take longer to detect antibody after infection than the HerpeSelect test.  It is a type-specific antibody test.

Timing of Antibody Testing   
    It is important to remember that the proper timing of testing is critical.  Let's say that a person had sex with a new partner and, three weeks later, they got a blood test for herpes.  The test value comes back at 0.9, which is negative.  The blood, however, may have been drawn too soon for an accurate test result.  If blood is redrawn three or four months after sexual exposure, the result might be strongly positive.  

    Sometimes getting a blood test for herpes can be difficult.  Some clinicians still don't know about the new blood tests, and may incorrectly tell patients that there is no way to diagnose herpes unless they are having symptoms.  Sometimes the wrong test is ordered like crude antigen tests or IgM tests.  Sometimes people feel odd about asking for the newest and best test.  If you're having difficulty getting one of the newer type-specific blood tests for herpes, there are websites where you can order a test yourself. A frequently used one that uses the correct test is www.healthcheckusa.com.  Remember, you want only IgG testing, not IgM testing, which is, unfortunately, also offered on that website.

General Suggestions about Diagnosis
    If you have questions about the tests that have been run on your behalf or any part of the exam, ask your clinician. The more you understand about what's going on, the less anxiety you'll feel in the long run.  A high level of anxiety during the diagnostic visit may make it hard to think of the right questions to ask.  If that happens to you, make a list of what you want to know, call back and ask your questions. You may find your clinician will have more time for your questions if you set up an appointment to go in for a consultation.