Assessing the risk factors

Genital herpes is caused by one of two herpes simplex viruses (HSV-1 or HSV-2), both of which are passed on from person-to-person through direct intimate contact.

Estimates indicate that 80% of people infected with genital herpes are undiagnosed and the disease is often passed on silently between partners. Poor diagnosis and lack of knowledge about genital herpes means it remains on the increase and is still one of the most common sexually transmitted diseases worldwide, with as many as 1 in 5 people infected across many countries.

The need for diagnosis

The majority of genital herpes infections remain largely undetected and undiagnosed. Studies have shown that a high percentage of people become infected from an undiagnosed partner, so improving diagnosis is therefore key in helping to reduce the spread of infection. Genital herpes often goes undiagnosed because of the wide range of symptoms associated with the infection, or because in some cases, there is a total absence of any visible signs or symptoms. Poor diagnosis can also be linked to a fear or embarrassment associated with having a sexually transmitted infection, which prevents some people from seeking medical help.

HSV-2 is the most common cause of genital herpes, whereas HSV-1 is the most common cause of facial herpes or cold sores, although cross infection can frequently occur. Being able to establish, through a diagnostic test, which virus is the cause of the infection is important because it will influence how the condition is managed. HSV-2 infection is more likely to recur in the genital area and therefore the patient may benefit from more frequent or continuous therapy known as suppressive therapy.

An accurate diagnosis can help people who are infected take control of their health and benefit from treatments that may reduce their symptoms and their frequency of recurrent infection. A confirmed diagnosis also means those infected may reduce the risks of passing the virus onto their partners, by recognising previously unrecognised symptoms and avoiding skin to skin contact at these times.

How to diagnose genital herpes

Diagnosis of genital herpes is made most easily and accurately at the time of an active herpes infection, preferably when symptoms are noticed for the first time.

This is because at this time, genital secretions and blisters containing fluid necessary for confirmation of infection are likely to be present, and a definitive diagnosis provides patient and doctor with the necessary information to agree the best course of treatment.

During the first appointment, the doctor will take a medical history, and perform a physical examination.

The physical examination - Classic signs of HSV infection such as fluid filled blisters or lesions are relatively easy to identify, however a physical examination is not always reliable because of the wide range of symptoms associated with the infection. Some of the signs of genital herpes can be confused with other conditions such as candidiasis (thrush), urinary tract infections or skin conditions affecting the genital area.

In order to confirm a diagnosis of genital HSV infection, it is necessary to prove the presence of the herpes simplex virus. Detection of HSV type specific antibodies in the bloodstream may be helpful but cannot define the site of HSV infection.

The usual procedure is for the doctor to perform a swab test, in which a sample of the fluid from a blister, from ulcers, or a sample of a genital secretion, is taken and sent away for analysis.

Laboratory analysis is usually made either by virus culture (where the virus is grown in material known as a culture medium) or by antigen detection where components of the virus are specifically identified.

Because it is possible for a person with genital herpes to have another sexually transmitted infection at the same time, a full genital check should be made. For women this may include a cervical smear test.

It is important to note that having genital herpes is not associated with the development of cervical cancer.

The physician may also use one or more of the following most commonly used methods to diagnose genital herpes, depending on each situation.

HSV-1 or HSV-2?

It’s useful to know whether your herpes symptoms are caused by HSV-1 or HSV-2, the major reason being that genital HSV-1 infection is less likely to cause frequent recurrent outbreaks. If you’re in the midst of a first episode, you might find it reassuring to know you’re dealing with the less troublesome of the two viral types. Determining viral type can be done in a number of ways (see below).

If your serologic test is positive for HSV-2, then the doctor will know that you have been infected with HSV-2 at some time in the past. It is highly likely that your HSV-2 infection is a genital infection for the simple reason that almost all HSV-2 infections are genital. This is true even if you’ve never experienced any genital symptoms.

If your serology is positive for HSV-1, the doctor will know that you have been infected with HSV-1 at some time in your life. While it is probably an oral or facial infection (even if you have no history of cold sores), you should be aware that a growing number of genital herpes infections are caused by HSV-1.

Diagnostic tests

Virus culture detection tests - This test involves using a moist cotton wool swab to collect a sample of virus from the infected area. The sample is then tested, usually in a laboratory. The problem with this detection method is that the person must have a ‘live’ or ‘active’ infection at the time of the swab test. If any blisters, lesions or ulcers have begun to heal the test may not give an accurate result. However, when active lesions are present, this method is seen as the gold standard diagnostic test.

Serology (blood) tests - When someone becomes infected with HSV the body will produce antibodies designed to fight the virus. These antibodies are specific to each virus, either Type 1 or Type 2, and remain permanently in the bloodstream. However it cannot indicate when or where on the body the initial infection took place, for example whether around the genital or facial area. Also antibodies take time to develop following initial exposure to a virus and for HSV-1 and 2 this is normally up to 3 months. Therefore if a blood test is carried out too soon after infection first takes place, it may give a false negative result, that is, come back negative, when in fact the person has been infected, but only recently.

The older blood tests could not reliably tell the difference between HSV-1 and HSV-2 type specific antibodies, as they only detected the presence of herpes simplex virus, but newer tests are now available which are type-specific and improve the accuracy of testing.

New herpes diagnostic tests - Type-specific blood tests are becoming more widely available. They can help to confirm a visual diagnosis of herpes and identify unrecognised cases where symptoms are either absent or difficult to define.

During 2001, a number of new tests were launched, although they are not yet available in every country. They include: the HerpeSelect®; type-specific HSV antibody detection test. These test kits work by taking a blood sample from the patient's arm and sending the sample to a laboratory for analysis. They can effectively distinguish between HSV-1 and HSV-2.¹ While these tests have high sensitivity and specificity, it is important to be aware that false positive and false negative results can occur.

After exposure, the time taken to develop HSV-specific antibodies is variable. In addition detection of HSV antibodies is variable depending on the test used. Test results therefore must be interpreted in light of the clinical situation and performed by an expert who knows how to interpret the results.

Type-specific HSV tests are not recommended for routine screening of the general public, but these tests can be helpful particularly in the following situations:

• For people who experience recurring genital signs/symptoms, but who have repeatedly negative cultures for HSV or other infectious agents.

• Where a partner has symptomatic genital herpes. This may be particularly important and/or helpful in pregnancy to ensure protection of the mother and baby. Please see the Herpes Simplex and Pregnancy leaflet in the Resources section of this website.

Because people's experience of genital herpes varies so greatly and because the treatment of any sexually transmitted infection is distinctive and specific, accurate diagnosis is essential.

While a blood test may reveal infection with HSV at a time when no genital symptoms are present, confirmation of genital HSV infection is still essential. If the blood test is specific for detection of antibodies to HSV type 2, the likelihood of genital HSV infection is increased, but still not proven. The doctor may ask you to re-visit for a swab test when genital symptoms or discomfort appear.

Useful information to discuss with your doctor if you are requesting a blood test.

• Ask whether the test is for HSV 1 and HSV 2 antibodies, or just for HSV 2 antibodies. If the blood test being done is only for HSV 2 antibodies a negative test does not rule out the possibility of the person having genital herpes caused by Type 1.
  
  
• Because false negatives and false positives can occur it is important that the doctor interprets the results in light of the clinical presentation and the patient’s history.
  
  
• Remember that the window period for antibodies developing following infection (depending which test is used) can be 2 weeks to 6 months.
  
  
• If you have the test and only HSV 1 antibodies are detected, the meaning of this is more difficult and needs to be discussed with your doctor. It may be due to past exposure to oral cold sores or herpes whitlow. If you think you have been exposed to genital herpes simplex, and you are unsure of whether it is Type 1 or Type 2 (as both can affect the genitals) this may leave many situations unable to be resolved.

Glossary of common terms

Below are some of the more common terms and products used when discussing testing, along with a brief explanation of each.

Seroconversion: This is the name of the process in a person who has developed antibodies to a particular infection (like herpes) that can be picked up by a blood test. Every person develops antibodies (seroconverts) at a different rate, so seroconversion happens at different times for different people. If a person has an infection but has not seroconverted, a blood test cannot pick up the antibodies and will read negative — even though the person is in fact infected. For most individuals with herpes, seroconversion will occur within four months of infection.

Type-specific serology: A blood test that can accurately distinguish between HSV-1 and HSV-2 antibodies and other herpes viruses.

Sensitivity: If a test is sensitive, the test is able to pick up antibodies if the antibodies are present. If a test is not sensitive, then the test will miss antibodies, and in turn, give a false negative result.

Specificity: If a test is specific, the test is not falsely picking up antibodies in a person that is not infected. If a test is not specific, the test will give a false positive result.

Accuracy: If a test is accurate, it is both sensitive and specific.

False negative: The test is negative in a person that actually has herpes.

False positive: The test is positive in a person that does not have herpes.

HerpeSelect®: An FDA-approved line of type-specific herpes antibody tests. Blood is drawn from the arm and sent to a laboratory; results are typically returned within one to four days.

Biokit

* Reproduced from American Social Health Association: fall 2001

Commercially Available Type-Specific Serologic Tests for HSV Antibody

Table reflects FDA-approved tests widely available as of January 2002. Range of scores reflects results from several studies using various standards of comparison.

1 — Sensitivity refers to a test's ability to detect the presence of antibodies whenever they are present. A sensitive test avoids false negatives.

2 — Specificity refers to a test's reliability in showing a positive result only when antibodies are present. A specific test avoids false positives.

Source: Data adapted from, Ashley RL, Sorting out the new HSV type-specific tests. Sex Trans Infect 2001; 77:232-237

For more information about new diagnostic tests please see www.herpeselect.com