Flawed herpes testing leads to false positives, needless suffering

Health

By Lindzi Wessel

Jan. 26, 2017

Various viruses from the herpes family seen using an electron microscope.
CDC
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Herpes is a lifelong infection, but Lauren had it only for six tumultuous months. Or rather, she believed she did, after a request for sexually transmitted disease testing returned a positive result. But after weeks of Googling, chatting with members of online herpes forums, and reading scientific papers, she asked for a different test, which eventually confirmed her suspicion — her herpes diagnosis was wrong.

In the six months that passed between the tests, the mistake led her to keep a romance at bay and left her anxiously patrolling her health.“Every tingle I would get in my leg or any kind of itch down there would just set me off,” sending her into a new flurry of research, she said. “And that was just to try to calm my own anxiety, but it would only really make it worse.”

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Genital herpes, predominantly caused by herpes simplex virus type 2, is a sexually transmitted disease that’s very common — 1 in 6 people aged 14 to 49 in the United States have HSV-2, and this number goes up with age. Most of these people, however, don’t have obvious symptoms and wouldn’t know they were carriers without blood tests.

But blood tests can be highly unreliable. The kind of test used to diagnose Lauren, an IgM test, has long been rejected by the Centers for Disease Control and Prevention but is still used by some clinicians. Meanwhile, the CDC and the US Preventive Services Task Force concur that the most widely available herpes test, called HerpeSelect, should not be used to screen asymptomatic people because of its high risk of false positives: Up to 1 in 2 positive tests could be false, according to the USPSTF’s most recent guidelines.

That high failure rate isn’t, however, always communicated to patients. Online forums abound with stories like Lauren’s, of people who request herpes tests alongside those of other STDs and are shellshocked by the results. Some doctors discourage the testing or simply don’t include it in a standard STD panel without having the conversation. But no data exists on herpes screening rates, according to Kimberly Workowski, lead author of the CDC’s STD treatment guidelines — so it’s difficult to say how many people could be living with the misdiagnosis.

A micrograph of herpes simplex virus in a Tzanck test specimen. CDC

Testing pitfalls

Next to the meandering waterways connecting Puget Sound to Seattle’s Lake Washington is the only laboratory in the world that offers to the public the Western blot, the gold standard test for herpes. The University of Washington Clinical Virology Laboratory provides the test to patients across the country, a practice it began over a decade ago when it realized the more common tests were prone to false positives.

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The problem, said Christine Johnston, a physician and researcher at the lab, is “low-positive” results of antibodies to HSV-2. The cutoff for a positive result on the HerpeSelect test, manufactured by Quest Diagnostics, is 1.1. A 2005 study published in the journal BioMed Central Infectious Disease found that index values above 3.5 yielded over 90 percent accuracy — but scores between 1.1 and 3.5 had around a 50 percent chance of being wrong.

What’s more, scores falling just above the 1.1 cutoff had an almost 90 percent chance of being wrong.

When tests fall between 1.1 and 3.5, more testing is necessary, said Johnston. This recommendation is also noted in the 2015 CDC Sexually Transmitted Diseases Treatment Guidelines. But some patients will never be referred for a second test.

“I think most clinicians are unaware and perhaps labs don’t have this available and/or it is not straightforward to order,” Johnston said of second-step tests.

But while her facility’s Western blot is considered highly accurate, it is expensive and cumbersome to perform. Each test costs over $200 and the University of Washington is the only lab that provides it.

Other confirmatory tests also exist, for instance Biokit’s HSV-2 Rapid Test and Quest’s own HSV-2 IgG Inhibition assay. The latter, which adds only $4 to the price of the HerpeSelect test, performed well in a study conducted over a decade ago. Rick Pesano, the medical director for infectious disease at Quest, believes that with more awareness, the test could stand in for the Western blot. But the test was not mentioned in the USPSTF guidelines because it still has not been evaluated in asymptomatic individuals, according to Cindy Feltner, associate director of the RTI-UNC Evidence-based Practice Center, who helped prepare the science review for USPSTF.

“We need better diagnostic testing. That is where we are stuck at this point,” said Johnston. “We don’t have a good test that’s inexpensive, high throughput, and reliable. ”

Finding out the hard way

No good data exist on how often patients with questionable positive results are actually re-tested. Until the 2015 update, CDC herpes testing guidelines had no mention of confirmatory testing for low-positive results, said Johnston. So patients often discovered the option not through their doctors, but through searching the web and reading online herpes forums.

That was the experience of Bryan, a 40-year-old man who lives in Indiana, who wrongly believed he had herpes for about two months in 2011. The misunderstanding actually put him at higher risk, he said: During those months he considered joining the hundreds of thousands of Americans on dating sites for herpes-positive people. Exclusively dating people with herpes would have increased his likelihood of contracting the virus.

The experience of YT, a 33-year-old mom who has suffered from frequent herpes symptoms over the last year, shows another side of the testing breakdown. She believes she was given HSV by a partner who didn’t realize herpes wasn’t included in his previous STD tests, she told STAT. Having herpes has caused her significant emotional trauma, and has driven her to permanently swear off dating. Had her partner known his true status, she wonders if her story would have been different.

These kinds of stories come out in anguished postings on internet forums and in dozens of confused calls to the UW lab each week, where research coordinator Matt Seymour says some desperate patients call over and over again, unable to get the answers they need from their doctors.

“People call and say, ‘I just don’t know what’s going on,’” he said. “We’ve almost become de facto counselors.”

Transmission electron microscope scan of cytomegalovirus particles. CDC

In the absence of answers

Herpes tests aren’t the only ones with a risk of false positive results. False positives can occur for any test that diagnoses viral infection based on antibodies, i. e., your body’s immune reaction, rather than direct detection of the virus. For similar diagnostics like HIV and hepatitis C testing, protocols automatically call for a second test that directly detects the virus whenever an antibody test comes back positive, said Paul Swenson, laboratory director in the department of public health of King County, Washington. Herpes, however, is a particularly challenging infection to directly test for, because the virus spends most of its time hiding in nerves. Swab tests can sometimes detect the virus during outbreaks, but this isn’t an option for people without symptoms. Thus even the Western blot relies on antibodies, and may give indeterminate results to a small number of people.

But two steps of antibody testing are still more reliable than one step; today’s diagnostics for Lyme disease and syphilis are a two-step antibody testing approach, said Dr. Edward Hook, a medical epidemiologist specializing in STI screening and prevention at the University of Alabama, Birmingham, who questioned why such a standardized two-step approach hasn’t taken firm hold for herpes.

“Some research has shown that two-step testing … might improve the specificity — that is avoid false positive results for the blood test — which would be a great thing because these diagnoses create great anxiety and concern for people,” he said. In a commentary accompanying the USPSTF guidelines, Hook expressed disappointment that herpes testing had barely improved over the past decade.

“There is no perfect test but there are ways to reduce the inaccuracies and reduce the number of equivocal results and those are actively used in other diseases,” he said in an interview with STAT. “But they haven’t been used very aggressively for the purpose of herpes.”

In the absence of sure-fire test advances, education and a lessening stigma surrounding herpes might help, not only by reducing test-related confusion, but potentially by bringing discussion of the virus out into the mainstream, said Hook.

“There’s no major herpes advocacy group,” he said. “People call attention to diseases that they suffer from, but people with herpes don’t feel they can call attention to it. And that creates a lot of suffering.”

About the Author

CDC – Genital Herpes Screening

Genital herpes is a common sexually transmitted infection (STI). Herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) cause genital herpes. Most people who have HSV-1 or HSV-2 don’t have symptoms.

People with symptoms can have one or more blisters on or around the genitals, rectum, or mouth. This is known as having an “outbreak.” The blisters break and leave painful sores that may take a week or more to heal.

There are a lot of questions about herpes tests. This page will help you understand CDC’s herpes testing recommendations.

Is it true that genital herpes is hard to diagnose?

Genital Herpes – CDC Basic Fact Sheet

Basic fact sheets are presented in plain language for individuals with general questions about sexually transmitted diseases.

Diagnosing genital herpes can be challenging. This is for two main reasons:

1. Many people with herpes have no symptoms

A healthcare provider may diagnose herpes by looking at any blisters or sores. They can also take a sample or swab from a blister or sore that is not already crusted over or healing. In fact, the tests that use these samples work best. However, most people with genital herpes do not have symptoms or can mistake them for other skin conditions like a pimple or ingrown hair.

2. There are limits to the current tests.

If a patient has no blisters or sores, providers may use a blood test to see if they have herpes. These tests have limits. For example, if a person gets a blood test too soon after an infection, the result could be wrong. A wrong result is also possible when the person has a low risk of infection.

If you’re sexually active, talk openly and honestly with your provider about testing for herpes and other STIs. They can help you decide what is best for you based on your sexual and medical history. These tips can help.

I found out my partner has herpes. When should I get tested?

Talk with your healthcare provider. In addition to recommending specific tests, they can also help guide when you should get tested. When someone gets genital herpes, it can take up to 16 weeks or more after an exposure for the current tests to detect it.

Genital herpes is common. Shouldn’t CDC recommend testing for everyone?

CDC recommends herpes testing for people who have genital symptoms to confirm if they have it. Testing allows a healthcare provider to talk with patients about what to expect in the future. This includes talking about medications that help with symptoms. Providers can also tell patients how to lower the risk of transmitting herpes to sex partner(s).

CDC does not recommend herpes testing for people without symptoms in most situations. This is because of the limits of a herpes blood test and the possibility of a wrong test result. The chances of wrong test results are higher for people who are at low risk of infection.

Blood tests might be useful if:

• You have genital symptoms that could be related to herpes, or
• You have (or have had) a sex partner with genital herpes, or
• Your provider found signs of herpes, but you still need a test to confirm it.

If you are sexually active, talk openly and honestly with your healthcare provider about what tests are right for you. These tips can help.

Does my healthcare provider include a blood test for genital herpes when they test me for “everything” (all STIs)?

Herpes blood tests may or may not be part of the tests your healthcare provider gives you. They may choose tests based on several factors (e.g., number of sex partners, if you had an STI before, etc.).

They will also evaluate you for signs or symptoms of herpes to choose which tests to use. This is why it’s important to talk openly and honestly with your provider during your visit. Ask them which infections they are and are not testing you for and why.

Additional Resources

• Sample questions you might ask your provider
• A list of questions your provider might ask you
• Conversation tips

Can testing and treating genital herpes decrease the risk for HIV infection?

No. Studies show that HIV risk is not lowered by genital herpes testing or treatment. Learn more about the link between genital herpes and HIV in this fact sheet.

Why are false positive tests an argument against routine testing for genital herpes, but not for other STIs, which can also have false positives?

False positive test results show that a person has an infection or condition when they do not. This can happen with many kinds of diagnostic tests. However, the chance of a false positive herpes test result is much higher than when testing for STIs like chlamydia or gonorrhea. This is because current herpes tests are not as exact as tests for chlamydia and gonorrhea.

I have genital herpes. Where can I find the latest information about ongoing genital herpes research, including clinical trials?

The U.S. National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) supports research to develop prevention methods and treatments for genital herpes. Details about current research efforts can be found on the NIAID website. NIH also maintains a database with information about clinical trials around the world. This database includes information on all genital herpes studies that are actively recruiting volunteers.

Herpes: causes, symptoms and recommendations for the treatment of the disease. Dr. Peter

• Directory of Diseases

July 6, 2022

Herpes simplex labial (on the lips) is a persistent viral infection. It is caused by contagious herpes simplex viruses, especially type 1 (HSV-1).

Source:

iStockphoto

An estimated 60 to 90 percent of adults worldwide carry this type of virus. After the first appearance of herpes on the lips or other areas of the face, it often reappears. Relapse is especially likely when the immune system is weakened or overwhelmed, such as from a cold or strenuous exercise.

Herpes labialis causes painful blisters, usually only on one side of the lip. This condition is sometimes erroneously referred to as a “cold” or “malaria” on the lips, even though it is a herpes infection. Treatment is usually not required, the rash resolves on its own within 1-2 weeks.

Herpes: causes

The disease is caused by contagious herpes simplex viruses (HSV). Many people carry these viruses but remain asymptomatic carriers all their lives. However, those people with labial herpes who suffer from rashes notice them with unenviable regularity.

There are two types, of which type 1 (HSV-1) is primarily responsible for labial (on the lips) herpes. Herpes simplex type 2 (HSV-2) causes rashes in the perineum, genitals, buttocks. Viruses are transmitted in fluid from blisters or bumps on the skin, such as kissing or sharing objects. Type 1 virus can be contracted through everyday contact, kissing, type 2 virus through sexual contact or through household items.

Herpesvirus types 1 and 2 migrate to the ganglia (nodes) of nearby nerves and stay there forever. A recurrence of herpes is especially likely when the immune system is weakened or overstrained, for example, as a result of a cold or heavy physical exertion.

Stress, hormonal fluctuations and skin irritation such as sunlight are also possible triggers. It is not entirely clear why some people re-sick with oral herpes and others do not.

Herpes symptoms

Herpes labialis causes painful blisters, usually only on one side of the lips. However, the blisters can also spread to the surrounding skin, mouth, or nose. In such cases, the blisters can easily burst and become wet when talking, laughing, or chewing. Various acidic liquids such as juice or vinegar, acidic foods can irritate the resulting lesions. As it heals, crusts form that fall off without scarring.

When herpes first occurs, it is often acute, and symptoms may include high fever and weakness or swollen lymph nodes in the neck. This is due to the fact that the body has not yet formed antibodies against the virus that causes the disease. This often happens in early childhood.

Primary infection with herpes labialis can cause severe inflammation of the oral mucosa. This inflammation is often painful, and there is a strong odor from the mouth.

Why herpes is dangerous

Herpes outbreaks usually occur once or twice a year. However, about 5-10 percent of people with cold sores have it more than 5 times a year. Symptoms often become milder over time.

In healthy people, herpes labialis resolves on its own and without further consequences. In people with skin conditions such as neurodermatitis or severe burns, the herpes virus can spread to large areas of the skin. But this rarely happens. A rarer case is inflammation of the eyes when, for example, keratitis.

If the immune system is very weak, for example due to chemotherapy, it is possible for the infection to spread throughout the body. In such cases, complications such as encephalitis, inflammation of the brain tissue, can occur.

Diagnosis of herpes

Labial herpes is easy to identify by typical symptoms. Anyone who has previously had “cold sores on the lips” usually knows by the first signs when an flare-up occurs again. A doctor’s consultation is usually not required. In rare cases, infection with herpes simplex type 1 viruses occurs in other areas of the skin. For diagnostic purposes, a doctor may take a sample of the fluid (swab) from the blisters and have it tested for herpes viruses in a laboratory.

How to treat herpes

Oral herpes usually does not require treatment. The condition goes away on its own. Antiviral ointments, gels, creams, and patches can shorten the duration of an acute attack by about one day. To some extent, they can also prevent the formation of blisters and scabs. These medicines contain the active ingredients acyclovir or penciclovir and are available without a prescription from pharmacies.

Proper use is important – for the medicines to be effective, treatment for herpes should be started within 24 hours of the onset of symptoms. It’s best to start as early as possible. Then the drugs are applied to the affected areas of the skin every 2-3 hours for 5 days.

Unlike drugs that are applied to the skin, antiviral tablets for the treatment of herpes are available only by prescription. These pills can also shorten the duration of an flare-up by about one day. Systemic therapy may be needed for more severe forms, the spread of the virus and its frequent recurrence.

Prevention

Some irritants can activate herpes simplex viruses and increase the risk of an exacerbation. Possible triggers:

• UV rays, such as from sunlight or tanning beds;

• Cold or fever;

• Minor injuries and cracks on the lips;

• Physical or mental stress;

• Taking cortisone anti-inflammatory drugs;

• Hormonal fluctuations, eg during the female menstrual cycle.

Anyone who wants to reduce their risk of oral herpes can try to avoid these factors. It is also helpful to try sunscreen and good lip care products. People who regularly suffer from labial or genital herpes should treat skin diseases in a timely manner, receive preventive therapy if relapses become more frequent.

Attention!

The information on this website is not a guide to self-medication. All materials are for reference only and do not replace a visit to the doctor. If any symptoms appear, you should contact a specialist.

References:

1. FGBU NIIDI FMBA of Russia. Clinical guidelines (treatment protocol) for the provision of medical care to children with an infection caused by the herpes simplex virus. – 2015. – 31 p.

2. Isakov V.A. Human herpesvirus infections: a guide for doctors / V.A. Isakov, E.I. Arkhipova, D.V. Isakov. – St. Petersburg: SpecLit, 2013. – 670 p.

3. Chayavichitsilp P., Buckwalter J.V., Krakowski A.C., Friedlander S.F. Herpes simplex // Pediatric Rev. — 2009; 30(4):119-129.

4. Semenova T.B. Principles of treatment of herpes simplex // BC. – 2002. – No. 20. – S. 924-931.

5. Ministry of Health of the Russian Federation. Clinical guidelines. Herpes simplex in adults. — 2016.

Blood test for herpes simplex virus type 1 and 2, IgM antibodies, semi-quantitative determination in Moscow

Herpes simplex virus (HSV, HSV) is a DNA-containing virus of the herpesvirus family. There are two types of virus: HSV-1 and HSV-2. HSV-1 manifests itself in the form of rashes of small vesicles in the mouth and in the oral cavity, eyes, skin, and much less often – damage to the genitals, as well as herpetic encephalitis and pneumonitis. HSV-2 manifests itself in the form of rashes of small vesicles in the genital area, disseminated herpes is less common.
Primary herpes is especially dangerous during pregnancy, since this significantly increases the risk of spontaneous abortion, severe damage to the fetus and newborn, and the formation of congenital abnormalities of the fetus. The presence of IgM antibodies to HSV 1/2 in the blood indicates a primary herpes virus infection or reactivation of a chronic process. If antibodies of the IgM class are detected, it is recommended to take an analysis for the detection of HSV 1/2 DNA and the determination of the avidity index of antibodies of the IgG class.

Infection with the herpes simplex virus occurs through contact with an area of ​​skin that has characteristic blisters. There is also a risk of infection through skin contact with an infected person who has no visible signs of infection. According to statistics, infection of adults with a type 1 virus is up to 80%, about 20% of people are infected with a type 2 virus. Often, the symptoms are mild, so many people are not aware of the presence of a herpes virus infection.
14 days after the first contact with the virus, small bubbles appear that cause discomfort. They usually go away within a month. Bubbles are localized on the buttocks, genitals, in the anus. In some cases, flu-like symptoms appear. Patients may complain of sore throat, chills, general malaise. Vesicle formation does not always occur. Sometimes they are absent or very weakly expressed. Often, the manifestations of herpes infection go unnoticed or are mistakenly perceived as an allergic reaction, mosquito bites. After infection and spread of the virus throughout the body, it remains in a latent form and does not cause any health problems. This may go on for years. Reactivation of the virus occurs only in the presence of predisposing factors. The impetus for the activation of the virus can be a decrease in immunity after an illness, severe stress, and so on.
Usually, HSV does not pose a serious health hazard. Infection of a child from the mother during childbirth is fraught with encephalitis and neonatal herpes. Complications of such diseases are serious neurological pathologies that can lead to death. Also, HSV can cause serious health problems in people with significantly reduced immunity.