How Can You Get an Accurate Herpes Blood Test?

How can you tell a 'type-specific' blood test from one that isn't type-specific?

Many of the herpes antibody tests available from health care providers are flawed: they do not accurately distinguish between HSV-1 and HSV-2. In fact, some of these tests will give a positive result for HSV-2 even when you have antibodies to only HSV-1. Others cannot detect HSV-2 antibodies when HSV-1 antibodies are also present. New tests are now available that are accurate. It is important to be sure that the laboratory your doctor uses is utilizing the best tests.

The new tests detect antibodies to a protein that differs between HSV-1 and HSV-2. This protein is glycoprotein G (or "gG") and the tests are sometimes referred to as the glycoprotein G specific or "gG-based" tests. Another test is the Western blot test. It also is very accurate. In fact, it is the test that most of the gG-based tests have been compared with to determine their accuracy. The Centers for Disease Control now recommend clinicians avoid blood tests that are not type specific. The best way to tell that a test is type-specific is to ask if it is based on glycoprotein G or to ask for one of the tests named in the next section.

Tests to Use

HerpeSelect® HSV-1 and HSV-2 ELISA Focus Technologies (Cypress, CA) makes and sells this test kit in the United States and many countries around the world. This test has been approved by the FDA for diagnosing HSV infection in adults, including pregnant women. The test takes less than a day once the specimen arrives in the laboratory. Many health care providers send blood specimens to local laboratories who then send specimens on to reference labs.

HerpSelect® immunoblot. This test is also produced by Focus and contains the same recombinant gG-1 and gG-2 that is used in the HerpeSelect ELISA kits. This test is also FDA approved but is used in smaller labs and some clinics. It detects antibodies to both HSV-1 and HSV-2 on a paper strip and is more expensive than the ELISAs. More can be learned about all of the HerpeSelect® tests at the herpeselect.com website.

Western blot. The other test available is the University of Washington's Western blot test. This test is is very accurate but is more expensive than the others and takes longer to perform. This test is not widely available and is not FDA approved. It is used as a reference test. However, it may be worth it to have your serum sent for Western blot if the HerpeSelect test result is indeterminate (not definitively positive or negative) or very low positive. Some local and reference labs will send specimens on to the UW Virology Lab for Western blot. Or, your provider may choose to send your serum directly.

biokit HSV-2 is the new name given to the test that was sold previously as "POCkit™HSV-2." The test is being offered by Biokit USA as biokit-HSV-2 and by Fisher Scientific under the brand name "SureVue." Thus, biokit HSV-2 and SureVue HSV-2 are the same test. This test can be performed in offices and clinics that have laboratory facilities. Only a couple drops of blood from a finger-stick is needed. This test requires about 10 minutes to perform and read.

Commercial gG-Based Type-Specific Tests for HSV Antibodies

FDA-Approved

HerpeSelect(TM) These are the packages from Focus Technologies’ tests. Note that the company has a label on the packaging to indicate that the tests are gG Based. This should help your health care provider and his/her laboratory to know that they have purchased one of the new type specific tests. These are actual immunoblot test strips photographed in the divided container used to perform the test. Each strip is a test for a different patient. The arrows point to the gG-2 (HSV-2) and gG-1 bands (HSV-1) on two of the strips. Most of the tests in the run have HSV-1 antibodies.

The biokit HSV-2 test is fast and easy to perform. This photo shows a positive patient result (right side of window) and control dot (left side of window). Normally positives are less red than the control dot, but can be as dark as the control dot. If HSV-2 antibodies are not present, only one red dot appears. Only one red dot represents a "negative" result. If a patient has only HSV-1 antibodies, the test will read "negative" with only one dot being red because this test does not contain gG-1. If neither dot turns red the test is invalid and must be repeated.

Western Blots From One Patient Over Time

These are Western blot tests from one patient who presented with recurrent HSV-2 infection (Year 0). At 1.1, 1.9, 3.2, and 8.2 years later, serum was drawn and tested again. The left-hand blot in each pair has HSV-1 proteins and the right-hand blot has HSV-2 proteins. Someone trained in Western blot will recognize the gG-2 band and also see that the gG-1 band is missing.

Commerical Type-Specific gG-Based Test Kits for HSV Antibodies

Not FDA-Approved

Steps to take to get an accurate serologic assay for HSV-2

Almost all laboratories require you to have the test ordered and the test results sent back to your healthcare provider. Usually this can be arranged through the staff in your provider's office.

Laboratory test. If your healthcare provider draws blood from your arm, the blood will first be centrifuged to remove the blood cells. The remaining fluid ("serum") contains the antibodies. The serum is then sent to a laboratory for testing. Ask the office to find out if the laboratory does the HSV-2 glycoprotein G HerpeSelect® ELISA or the Western blot test. A few on-site clinic laboratories use the HerpeSelect immunoblot® test.

If your provider's laboratory does not offer HerpeSelect® or Western blot testing, then ask the office to send the blood to a laboratory that does do one of these tests. The HerpeSelect® ELISA is now used by most major reference testing laboratories. Labcorp, a major commercial testing lab, unfortunately offers a non-typing test followed by HerpeSelect for HSV-2 (not HSV-1). Your provider must clearly request the HerpeSelect test from Labcorp to be sure of getting as accurate HSV-2 test in the shortest time.

Reference Laboratories Offering HerpeSelect® Tests

• Quest (lists HerpeSelect® by brand name)
• Mayo Clinic
• ARUP
• Specialty Labs
• Unilab/Tarzana
• American Medical Labs

Reference Test: Western blot. To get a Western blot directly from the UW laboratory, have your provider call the 800-713-5198. http://depts.washington.edu/rspvirus/ The UW laboratory personnel will send out special forms and a special mailing tube. The forms must be completed including billing information. When this material arrives in the healthcare provider's office, have your blood drawn and processed so that the serum can be sent to Seattle. It can be mailed in a special pack. Once the serum arrives in the laboratory, Western blot takes about 4-5 days. About 1 in 5 samples requires further testing, which requires an additional 5-7 days. The test results must go to a healthcare provider. The results will be mailed or faxed back to your provider.

Interpreting the gG Serology

Test results from one of the glycoprotein G specific tests (HerpeSelect® or ELISA or Immunoblot) are as follows:

HSV-2 Antibodies Present: This means you have HSV-2 infection, the virus is dormant in your sacral nerves and you have genital herpes.

HSV-2 Antibodies NOT Present: This means with 95-98% accuracy you do not have genital herpes unless you acquired it very recently. New studies have shown that by 6 weeks after HSV-2 infection, 60-75% of patients will be positive by the HerpeSelect® test but for a few patients (about one in 5), it can take as long as 6 months to develop antibodies. Once antibodies are made, the test stays positive. If you might have acquired herpes very recently, you may need to repeat the antibody test in 6-8 weeks.

HSV-1 Antibodies Present: This means you have HSV-1 infection. The antibody assay cannot tell where HSV-1 is dormant in your body. In most people (>90%) it is in the nerves of the mouth and eyes. Some people do have genital HSV-1 and could have HSV-1 antibodies from genital HSV-1 infection. (Click here to learn more about genital HSV-1 Infection)

Neither HSV-1 or HSV-2 Antibodies Present: You are not infected with either HSV-1 or HSV-2 but you are susceptible to getting infection. There is a small chance that you may have been recently infected, but have not made antibodies yet.

Less Accurate Tests

The table below lists companies who offer tests that do not perform well for HSV-1 and HSV-2 antibodies. There is a good chance that the wrong type of HSV antibody will be diagnosed or that antibodies to HSV-2 will be missed by these tests. Patients with previous antibodies to HSV-1 (made in response to oral herpes or "cold sores") who acquire HSV-2 genital herpes are most likely to be misdiagnosed by these tests as "HSV-1 only". Thus, many HSV-2 infections will not be detected by these tests.

You should be aware that to be licensed, laboratories have to pass proficiency tests to show that their testing is accurate. In a recent proficiency test from the College of American Pathologists (CAP) only HerpeSelect and Western blot tests were 100% accurate. Many test results from laboratories using other tests for type specific serology were incorrect.

Some companies like Diamedix have reformatted their tests so that no attempt is made to differentiate between HSV-1 and HSV-2 antibodies. This type of test can be a good first step to tell if a patient has had either HSV-1 or HSV-2 infection but, eventually, for accurate diagnosis of HSV-2 genital herpes, a gG-based type-specific serology is best.

Other companies warn consumers in their test inserts that the test results should not be used to differentiate HSV-1 and HSV-2 antibodies. It is very unlikely that clinicians or patients will have the opportunity to read these warnings. Also, laboratories continue to use these tests and to give a result for HSV-1 and for HSV-2 antibody status based on these tests. Your provider should be able to find out what kit the laboratory will use on your test. If it is one of the following kits, your test is not a gG-based test and the results may not be accurate.

Antibody Tests Based on Crude Antigens (Not Recommended)

What is my chance for getting an inaccurate result with these non-gG tests?

If herpes is so widespread, should everybody be tested?

Screening for herpes in the general population is not recommended as of now, and guidelines for antibody testing are still being developed. Experts in the field have specified the following situations that might warrant serologic tests:

• Confirming infection in a person who has had symptoms but never had a positive confirmatory test result.
• Determining if a person is at risk of having acquired herpes because their partner has been diagnosed with herpes.
• Detecting herpes as part of a work-up for STDs.
• Helping to determine a pregnant woman's risk of passing herpes to a newborn.
• Confirming that a partner of a person taking antiviral medicines to suppress herpes shedding is susceptible to infection.