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Laboratory professionals should recommend type-specific gG-based serology tests to facilitate the diagnosis and treatment of genital herpes infections.

As the clinical diagnosis of HSV is not sensitive or specific enough for a definitive diagnosis, healthcare providers rely on the laboratory to provide accurate diagnostic test results and information.

Laboratories should offer both viral culture and blood serology tests.

Viral culture is the gold standard test for detecting HSV in new lesions and a positive culture result is generally reliable. But culture alone is often unreliable in patients with recurrent infection or healing lesions and up to 70% of culture results can be falsely negative.

Serology tests provide physicians with the information they need to accurately diagnosis HSV infections.

Serology is critical when:

  • Lesions are negative or not sampled for virus
  • Symptoms suggest atypical or undiagnosed herpes
  • Lesions appear herpetic but may have other etiology

Type-specific serology tests provide physicians with the information they need to establish treatment options and provide appropriate patient counseling.

  • Type-specific serology can accurately differentiate HSV type-1 from HSV type-2. Both HSV type-1 and HSV type-2 can cause genital herpes infection.
  • During pregnancy, type-specific serology can identify women at risk of acquiring genital HSV type-1 or HSV type-2 infections close to term.
  • Treatment recommendations may vary based upon type-specificity as outbreak frequency is often higher with HSV type-2 genital infections than with HSV type-1 infections.
  • Patient counseling may vary based upon type-specificity:
    • prognosis and status of sexual health
    • risk of transmission to partner
    • risk of acquiring genital herpes during pregnancy/transmission to baby
    • behavior modification

Laboratory professionals should make sure that the serology tests they offer are glycoprotein G, (gG), type-specific serology.

Some serology tests claim type-specificity, but most do not accurately differentiate HSV type-1 antibodies from HSV type-2 antibodies. Healthcare Providers depend on their lab to offer the best test available. There are several ways you can tell if the kit you offer is gG type-specific:

  • Look in the kit insert for confirmation that the kit is FDA-cleared for type-specificity.
  • The kit manufacturer offers two separate kits for HSV type-1 and HSV type-2 detection and specifies that they incorporate gG-based technology.
  • Visit this website ( www.herpesdiagnosis.com/blood.html) ) for a specific list of kits that do not utilize gG-based technology.

HerpeSelect is the first gG type-specific serology test for both HSV type-1 and HSV type-2 to be FDA-cleared for both pregnant mothers and sexually active adults.

HerpeSelect is the only gG-based kit FDA-cleared for use on automated platforms to assist in improving laboratory workflow and efficiency.

HerpeSelect has been used to perform type-specific HSV testing throughout laboratories in the US since February, 2000.




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Meet Your Host
Wayne Hogrefe, Ph.D.
Director, Scientific Affairs and Technical Services

Dr. Hogrefe has served in a number of key positions in R&D and clinical immunology at Focus Diagnostics, leading to his current role as Director of Scientific Affairs and Technical Services. He participated in the early development of recombinant glycoprotein-G1 and gG2 that enabled clinical laboratories to perform accurate type-specific serology testing for HSV type-1 and type-2. Dr. Hogrefe's body of research has focused on development of solid-phase ELISA assays for detection of post-vaccine antibody responses to polysaccharide antigens, autoimmune diseases, and viral serologic screening assays. Dr. Hogrefe’s research has been published in numerous peer-reviewed journals, and he is a highly respected and in-demand speaker on a number of scientific topics, including herpes diagnostic testing.

Dr. Hogrefe received his Ph.D. in Experimental Pathology from Case Western Reserve University, and was involved with the early studies of cancer immunity and associated host suppressor response. Former positions include Associate Director of the Immunopathy Laboratory at St. Luke's Hospital, Cleveland, Ohio and Assistant Clinical Professor at the Case Western Reserve School of Medicine.

Dr. Hogrefe has served as a Board Member, Exam Committee at the American Board of Medical Laboratory Immunology, and several committees on Education, Quality Assurance and Animal Resource.

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Herpes Facts

The Herpes Virus Family

There are eight herpes viruses currently known to infect humans. These include; herpes simplex virus type-1 (HSV type-1), commonly associated with cold sores or fever blisters; HSV type-2, most commonly associated with genital herpes; varicella zoster virus, which causes chickenpox and shingles; cytomegalovirus (CMV), associated with retinitis and pneumonia in immunocompromised people; Epstein-Barr virus, which causes infectious mononucleosis; human herpesvirus 6 (HHV6), causing childhood roseola; HHV7, which results in infectious mononucleosis in children; and HHV8, associated with Kaposi’s sarcoma. Despite the extensive range of symptoms of herpes virus infections, all are characterized by the establishment of latent infection and all have the potential to reactivate from latency.

Herpes simplex virus type-1: commonly causes herpes labialis (also called oral herpes, cold sores or fever blisters), which are highly infectious open sores that crust over before healing. Although less probable, HSV type-1 can also cause genital herpes.

Herpes simplex virus type-2: a contagious sexually transmitted viral infection primarily causing genital herpes in men and women. The telltale signs of genital herpes include recurrent clusters of blisters, bumps and rashes in the genital areas and rectal lesions. HSV type-2 can also be responsible for herpes labialis, although less often than HSV type-1.

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Structure of the Virus


The HSV type-1 and HSV type-2 viruses look identical by the electron microscope.

The glycoprotein G (gG) protein is unique to HSV type-1 and HSV type-2. Serologic tests that use glycoprotein G-based technology accurately discriminate antibodies due to HSV type-1 from antibodies due to HSV type-2. The gG protein should not be confused with immunoglobin G (IgG). IgG and other antibody classes (e.g. IgA and IgM) are elicited by gG.

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Genital Herpes Symptoms

Most people with genital herpes are unaware that they have the disease because they never have symptoms or do not recognize them. When they do occur, the symptoms (and severity) of genital herpes vary from person to person. First episode symptoms of genital herpes can appear within 2 to 10 days of infection and last an average of 2 to 3 weeks. In many people, the first infection may be so mild that it goes unnoticed. In other people, painful sores may appear at the site of infection. Other symptoms can include tingling, an itching or burning sensation; pain in the thighs, buttocks, or genital area; vaginal discharge; a feeling of pressure in the abdominal area; flu-like symptoms (which may include swollen glands, headache, muscle ache or fever;) and painful or difficult urination. Genital herpes symptoms are sometimes mistaken for simple skin irritation, jock itch, razor burn, or a yeast infection.

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Transmission

HSV type-1 and HSV type-2 is released from the sores that the viruses cause, but they also are released between episodes from skin that does not appear to be broken or to have a sore. A person almost always gets HSV type-2 infection during sexual contact with someone who has a genital HSV type-2 infection. A person can get HSV type-1 by coming into contact with the saliva of an infected person. HSV type-1 infection of the genitals is caused by oral-genital sexual contact with a person who has the oral HSV type-1 infection or genital contact with a person who has genital HSV type-1 infection.

Increased risk of HIV with HSV type-2 infection

There is significant evidence that there is synergism between HSV type-2 and HIV-1. These findings are bringing about a fundamental change in physicians views about the importance of Herpes testing. The paradigm shift means that concerns of physicians and health officials are in concert with those of patients with known genital herpes infections who have been concerned about transmission of the disease. Almost all new cases of genital herpes are transmitted by a person who is unaware of their HSV type-2 status. Type specific testing is important so treatment can be instituted. 

To date, there have been over 30 studies that have determined the risk for HIV acquisition among persons with HSV type-2 is fairly high. In international studies, there is the establishment of linkage.

HSV type-2 has a different natural history among HIV-infected persons. Those individuals that have both infections have more frequent HSV type-2 activations, at much higher rates of viral shedding. Finally, there are some data that HSV type-2 is associated with increased HIV plasma levels in people who have both infections. HSV type-2 may be one of the core factors to determine the progression and natural history of HIV disease. There are some early indications that suggest that treatment for HSV may be associated with reductions in plasma HIV levels.

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Facts and Statistics

Transmission of the disease:

  • 1 in 6 people worldwide have genital herpes caused by HSV type-2.
  • HSV type-2 infects more than 1 of every 5 people in the US
  • About 70% of people contracting herpes get it from a partner who is unaware they have it at the time they transmit the disease.
  • Both HSV type-1 and HSV type-2 can cause genital infection.
  • Genital herpes can be transmitted by genital or oral sex (cold sores).
  • Viral shedding in the absence of symptoms can transmit infection.
  • Transmission of herpes can occur within committed long-term relationships and in people who have never had penetrative sex through close genital contact or oral-genital contact.
  • Condoms reduce the risk of transmission, but it is also advisable to avoid skin to skin contact when lesions are present.
  • HSV type-2 infection increases the risk of HIV infection.

Diagnosis:

  • Up to 90% of all HSV type-2 infections go unnoticed or undiagnosed because of mild or absent symptoms.
  • Up to 20% of first episodes are actually reactivation of previously latent infection rather than recently acquired primary infection.
  • HSV culture can frequently give false negative results.
  • Accurate, type-specific serology tests can detect asymptomatic infection.

Recurrences:

  • People who experience a first episode will get better. Lesions will heal and recurrences will usually be less severe.
  • HSV type-2 may reactivate more frequently than HSV type-1.
  • Antiviral treatment can minimize and/or prevent HSV outbreak.

Pregnancy:

  • Genital herpes does not cause cervical cancer or affect fertility.
  • First episode genital maternal HSV infection poses a threat to the baby.
  • Neonatal herpes is serious but rare.
  • Women with genital herpes can have a safe pregnancy and vaginal delivery.
  • New infections need close medical follow-up.



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Diagnosis Guidelines

Any person who has been sexually active may have contracted genital herpes. Diagnosis should be strongly considered in those with:

  • More than five lifetime sexual partners
  • A partner with known genital herpes
  • Any recurrent lesions or symptoms in the area of the sacral dermatomes
  • A history of STD or HIV infection.

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Diagnostic Algorithm

2006 CDC STD Treatment Guidelines excerpt:

"Both virologic and type-specific serologic tests for HSV should be available in clinical settings that provide patient care for patients with STDs or those at risk for STDs."

> Click here to print the Diagnostic Algorithm chart below.

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CDC Sexually Transmitted Diseases Treatment Guidelines
(as printed in the Morbidity and Mortality Weekly Report)

CDC Guidelines excerpts*:

"... the clinical diagnosis of genital herpes should be confirmed by laboratory testing. Both virologic tests and type-specific serologic tests for HSV should be available in clinical settings ..."

"Because false-negative HSV cultures are common, especially in patients with recurrent infection or with healing lesions, type-specific serologic tests are useful ..."

"... older assays that do not accurately distinguish HSV type-1 from HSV type-2 antibody, despite claims to the contrary remain on the market."

"... serologic type-specific gG-based assays should be specifically requested when serology is performed."

The MMWR series of publications is published by the Epidemiology Program Office, Centers for Disease Control and Prevention (CDC), US Department of Health and Human Services, Atlanta GA 3033.

*Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11):[page 16].

To view the complete report, please go to:
> http://www.cdc.gov/STD/treatment/2006/rr5511.pdf

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Summary Guidelines for the Use of Herpes Simplex Virus (HSV) type-2 Serologies
(published by the California STD Controllers Association and California Department of Health Services, 2004)

California Guidelines Summary:

Recommended Use of HSV type-2 Serologies For Diagnosis and Screening

  • Diagnosis of genital lesions/symptoms: type-specific serology tests should be available for diagnostic purposes in conjunction with virologic tests at any setting where patients are evaluated for STDs.
  • Screening in patients at-risk for STD/HIV (Current STD, recent STD, high-risk behaviors): shoud be offered to select patients
  • Screening in HIV-positive patients: should be generally offered.
  • Universal screeing in pregnancy: should generally not be offered.
  • Screening in general population: should generally not be offered.
  • Herpes education and prevention/transmission counseling is necessary for all people being tested or screened for HSV type-2.
To view the complete report , please go to http://www.stdhivtraining.org



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Laboratory Tests

The clinical diagnosis of genital herpes is both insensitive and non-specific. Therefore the clinical diagnosis of genital herpes should be confirmed by laboratory testing. Clinical laboratories should offer both virus detection tests and antibody detection tests.

Virus Detection

Virus detection tests begin by vigorously swabbing lesion sites to collect cells containing HSV. Viral detection tests include:

Conventional Culture (viable virus)

Isolation of HSV in cell culture is the preferred HSV test of most healthcare providers. Cell culture requires the collection of live virus samples that require special care in transport to the laboratory to retain viability. When viable samples are used, culture can be highly specific (if typing is performed) and positive results are generally reliable. The sensitivity of culture declines rapidly as lesions begin to heal and for this reason frequently non-positive results are falsely negative. Type-specific serology tests should be used in these cases to confirm a clinical diagnosis of genital herpes.

Modified Culture

  • Shell Vial: A centifugation enhanced culture technique used to obtain rapid culture results. Generally less sensitive than conventional culture.
  • ELVIS® (Enzyme-Linked Virus Inducible System): A technique which combines cell culture amplification with HSV-activated reporter genes. The test produces results which are equal to conventional culture.

Antigen Detection (virus antigen)

The common methods used in antigen detection are:

  • Immunofluorescent (IFA) and immunoperoxidase (IPA) assays which detect HSV antigen in smears or tissues. HSV-specific antibodies are labeled with fluorescent dyes or enzymes (peroxidase). The labeled antibodies are incubated with the specimen and bind to HSV antigens in the specimen, if present. The attached fluorescent dye or enzyme can be visualized in appropriate regions of infected cells under a microscope.
  • Enzyme Immunoassays, (EIA or ELISA) are done on fluids or other samples using HSV-specific antibody that is bound to a solid surface. The antibody captures antigen to which anti-HSV antibodies labeled with enzymes are added. These attach to the bound antigen and cause a color change.

These tests are inexpensive and rapid, but have relatively low sensitivity and lack usefulness in asymptomatic patients.

Polymerase Chain Reaction

Polymerase Chain Reaction or PCR (virus nucleic acid, DNA) tests are highly sensitive but expensive to perform and therefore, not suited to routine use. PCR amplifies small amounts of virus type-specific DNA to easily detectable levels using pre-prepared genetic sequences unique to HSV type-1 or HSV type-2. PCR is recommended for use in diagnosing CNS infections of neonates by testing cerebrospinal fluid.

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Antibody Detection

Antibody Detection or serology tests involve the detection of antibodies to HSV in the blood. Both type-specific and nonspecific antibodies to HSV develop during the first several weeks following infection and remain in the blood indefinitely. During primary infection, the first antibodies produced belong to the IgM class. The presence of IgM antibodies in HSV infections is difficult to interpret and may be confusing because unlike IgG, IgM antibodies are not type-specific. The presence of IgM antibodies may indicate a true primary infection, a super-infection with the other serotype, or reactivation of a latent HSV infection, (HSV type-1 or HSV type-2). For this reason, IgM testing is not recommended as a diagnostic tool.

IgG antibody detection, or serology tests, are an important adjunct to virus detection methods in patients with no obvious symptoms. The following tests are in this category:

Type-common (crude antigen) serology tests measure HSV antibodies in the blood but are unable to distinguish between HSV type-1 and HSV type-2 infection though labeled as if they could distinguish. Detection of antibodies can be useful to diagnose HSV infection when culture, virus antigen detection or PCR yield negative results, but are not helpful in making a definitive diagnosis of genital herpes in a patient with prior oral HSV type-1 infection.

Type-specific serology tests are those that accurately distinguish between HSV type-1 and HSV type-2 antibodies.

The advent of recombinant technology has enabled production of highly purified preparations of the HSV type-specific antigens gG1 and gG2, and these antigens can be used to detect HSV type-specific IgG antibodies. Sera from individuals infected with only HSV type-1 will react only with gG1, sera from individuals infected with only HSV type-2 will only react with gG2, and sera from individuals infected with both HSV type-1 and HSV type-2 will react with both gG1 and gG2. Type-specific HSV IgG assessment is a valuable tool for the accurate identification of the type(s) of HSV responsible for infection.

The Western Blot assay for HSV is highly accurate in differentiating HSV type-1 and HSV type-2 antibodies when used with a step to cross-adsorb antibodies to HSV type-1 and HSV type-2 antigens. However, it is expensive to perform, takes several days, and is not commercially available. The provider of Western Blot testing services is the University of Washington.

There are several type-specific ELISA (enzyme immunoassay) tests commercially available that are relatively easy to perform in the laboratory and give results quickly. Type-specific assays for HSV antibodies must be based on the HSV-specific glycoprotein G2 to accurately diagnose infection with HSV type-2 and with glycoprotein G1 to accurately diagnose HSV type-1.

HerpeSelect, from Focus Diagnostics offers two FDA-cleared lab-based assay formats for detecting type-specific HSV IgG antibodies: HerpeSelect Immunoblot uses purified recombinant type-specific gG-1 and gG-2 antigens, and native HSV common antigens immobilized on nitrocellulose membranes. HerpeSelect ELISA consists of two micro-plate assays, one for detecting antibodies to HSV type-1 (gG1), and the other for antibodies to HSV type-2 (gG2). Both assay formats had sensitivity and specificity values ranging from 91-100% in clinical trials with sexually active adults and pregnant women.

Other FDA-cleared gG-based type-specific assays are available. Trinity Biotech manufactures HSV type-1 and type-2 kits, which have recently received FDA clearance. A type-specific HSV-2 assay, formerly available from Diagnology (POCkit®), is expected to be reintroduced soon by another manufacturer.

Serological tests for HSV only indicate prior infection and do not identify the site of infection. These tests may give false-negative results in the early stages of infection because antibodies may not reach detectable levels for 8 weeks or longer. False-positive results can also occur in patients with low likelihood of HSV infection. Repeat testing or a confirmatory test may be indicated in some cases.




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HerpeSelect

About HerpeSelect

Until recently, there hasn’t been a reliable serologic tool for differentiating antibodies for HSV type-1 from HSV type-2 infection. Most commercial methods use shared or type-common antigens, which react with both type-1 and type-2 antibodies. To be truly type-specific, a diagnostic method must recognize antibodies to glycoprotein G1, found only on HSV type-1 virus and glycoprotein G2, found only on HSV type-2 virus.

HerpeSelect is the brand name of two FDA-cleared diagnostic test kits manufactured by Focus Diagnostics. HerpeSelect tests utilize highly purified preparations of the HSV type-specific antigens, glycoprotein G1 and glycoprotein G2. These antigens are used to detect HSV type-specific antibodies. HerpeSelect HSV serology tests for both HSV type-1 and HSV type-2 are FDA-cleared for expectant mothers and sexually active adults and designed for use by clinical laboratories.

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Test Kits

HerpeSelect type-specific HSV IgG antibody detection kits are available in two assay formats:

For type-specific HSV testing in higher volume laboratories:

  • HerpeSelect 1 ELISA (96 wells/kit)
  • HerpeSelect 2 ELISA (96 wells/kit)


The HerpeSelect ELISA Kit

For differentiating HSV type-1 and HSV type-2 in a single specimen (low volume testing):

  • HerpeSelect 1 & 2 Immunoblot (24 strips/kit)
 
The HerpeSelect
Immunoblot Kit
  A Single HerpeSelect Immunoblot Patient Strip

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Performance Characteristics

HerpeSelect assays are designed to:

  • Identify individuals, including pregnant women, and their partners that are at risk for infection,
  • Aid in the diagnosis of infected expectant mothers who could transmit virus during labor, and
  • Aid in the diagnosis of individuals, with or without typical genital symptoms, who could transmit virus to a sexual partner.

Both assay formats had sensitivity and specificity values ranging from 91-100% in clinical trials with sexually active adults and pregnant women.

HerpeSelect ELISA Performance

Compared to Western Blot or CDC Panel

HSV type-1

HSV type-2

Sensitivity

Specificity

Sensitivity

Specificity

Pregnant Women

96

95

100

96

Sexually Active Adults

91

92

96

97

CDC Panel*

93

100

100

100


HerpeSelect Immunoblot Performance

Compared to Western Blot or CDC Panel

HSV type-1

HSV type-2

Sensitivity

Specificity

Sensitivity

Specificity

Pregnant Women

100

93

100

94

Sexually Active Adults

99

95

97

98

CDC Panel*

100

100

100

98

* The CDC panel results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

Serological tests for HSV only indicate prior infection and cannot identify the site of infection. These tests may give false-negative results in the early stages of infection because antibodies may not reach detectable levels for 8 weeks or longer. False-positive results can also occur in patients with low likelihood of HSV infection. Repeat testing or a confirmatory test may be indicated in some cases.

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Equipment Needed

HerpeSelect ELISA:

  • 10µl, 100µl, 1ml and 5ml pipettes
  • ELISA plate spectophotometer with 450nm wavelength filter
  • Optional equipment: automated ELISA reader

HerpeSelect Immunoblot:

  • 15µl and 5ml pipettes
  • platform rocker

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Kits Inserts

Please click the links below to view the package inserts.

  • HerpeSelect 1 ELISA Kit
  • HerpeSelect 2 ELISA Kit
  • HerpeSelect 1 & 2 Immunoblot Kit

The inserts are available in Adobe Acrobat Portable Document Format (PDF).
For the latest version of Acrobat Reader please follow the link below:

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Order Information

HerpeSelect Tests are available from Focus Diagnostics.
Click here to go to Focus Diagnostics' Reference Laboratory Online Catalog.

To purchase HerpeSelect test kits, contact Focus Diagnostics Customer Service at (800)838-4548 (within the US), (714)220-1900, or fax (714)220-1820.

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Availability

HerpeSelect test kits are used in commercial and hospital laboratories throughout the US. Although many labs offer these assays under the brand name HerpeSelect, others utilize the HerpeSelect test kit but offer the test under a more generic methodology name such as HSV type-1 or HSV type-2 type-specific ELISA. Make certain that your laboratory utilizes an FDA-cleared glycoprotein-G based assay that accurately discriminates IgG antibodies from HSV type-1 and HSV type-2 infections.

For further information about what labs offer HerpeSelect testing, please contact Focus Diagnostics’ HSV Information Center at (800) 505-0536. For information about testing at Focus Diagnostics please call Client Service at (800) 838-4548 (within the US), (714) 220-1900 or fax us at (714) 220-1820.

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FDA Clearance

HerpeSelect HSV type-specific serology tests for both HSV type-1 and HSV type-2 are FDA-cleared for both sexually active adults and expectant mothers.

HerpeSelect assays are cleared for use on automated instrumentation. The user needs to validate performance on their equipment.

View FDA clearance letters:

  • HerpeSelect FDA ELISA 1 Approval
  • HerpeSelect FDA ELISA 1 Automation Approval
  • HerpeSelect FDA ELISA 2 Approval
  • HerpeSelect FDA ELISA 2 Automation Approval
  • HerpeSelect FDA Immunoblot Approval

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CPT Codes

2002 CPT Codes are listed for guidance purposes only. For further reference, please consult the CPT Coding Manual published by the American Medical Association.

  • CPT Code 86695    Antibody, herpes simplex, type-1
  • CPT Code 86696    Antibody, herpes simplex, type-2

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Frequently Asked Questions

What differentiates HerpeSelect from other test kits?

Many laboratories offer HSV type-1 or HSV type-2 IgG antibody testing, but their tests are not able to deliver reliable type-specific results. Reactivity with shared, type-common antigens is almost always present to some degree, causing inaccurate results to be reported in up to 70% of positive patients. HerpeSelect 1 and 2 kits use glycoprotein G antigens -- gG1 (from HSV type-1) and gG2 (from HSV type-2) – the major antigens known to elicit type-specific antibody responses. HerpeSelect® HSV type-1 and HSV type-2 type-specific tests are FDA-cleared.

What is the difference between HerpeSelect ELISA and HerpeSelect Immunoblot?

HerpeSelect ELISA system consists of two micro-plate assays, one for detecting HSV type-1 (gG1) IgG, and the other for HSV type-2 (gG2) IgG. These tests are appropriate for high volume testing on automated platforms and individual antibody type testing.

ELISA

  • 2 separate kits (HSV type-1 or HSV type-2)
  • 96 test wells per kit in breakaway strips
  • Numerical result
  • CLIA rated highly complex

HerpeSelect 1 & 2 Immunoblot IgG is like a simplified Western Blot with gG1 and gG2 bands, a type-common HSV band, and a serum control band all arrayed on a single strip. The test is read visually for HSV type-1 and HSV type-2 results so that instrumentation is not required. It is well suited for lower volume laboratory testing.

Immunoblot

  • 1 kit for both (HSV type-1 & HSV type-2)
  • 24 test strips per kit
  • Positive/Negative result visually read on nitrocellulose strip
  • CLIA rated moderately complex

What type of equipment is needed for HerpeSelect testing?

For the ELISA tests, 10ul, 100ul, 1ml and 5ml pipettes are needed. A microplate (450nm) reader is needed to read the ELISA test result. HerpeSelect is now FDA-cleared for use on automated instrumentation. Performance characteristics should be established by the user for their equipment.

For the Immunoblot test, 15ul and 5ml pipettes are needed, as well as a platform rocker.

How long does it take to perform HerpeSelect testing?

Both tests are performed in less than 3 hours.

Is HerpeSelect Immunoblot a confirmatory test for HerpeSelect ELISA?

No. Both formats exhibit sensitivity and specificity values ranging from 91-100% in clinical trials with sexually active adults and pregnant women.

How much does a HerpeSelect test cost?

For information on kit prices contact Focus Diagnostics at (800) 838-4548.

For information on HerpeSelect testing services from Focus Diagnostics clinical laboratory, call (800) 445-4032.

Is HerpeSelect reimbursed by payors?

An example of reimbursement is:

Medicare Part B, 2004 Fee Schedule:
HSV type-1    CPT Code 86695    $18.91
HSV type-2    CPT Code 86696    $27.75

Can a patient order HerpeSelect Kits?

No. But, for more information on how to get HerpeSelect testing patients may contact Focus Diagnostics Customer Service at (800) 445-4032 (within the US), (714) 220-1900 or fax (714) 220-1820.

How long after infection will HerpeSelect detect IgG antibodies?

Recent studies show that HerpeSelect can detect HSV IgG antibodies as quickly as 3 weeks after onset of symptoms.

What about HSV IgM testing?

The presence of IgM antibodies in HSV infections is difficult to interpret and may be confusing because unlike IgG, IgM is not type-specific. The presence of IgM may indicate a true primary infection, a super-infection with the other serotype, or reactivation of a latent HSV infection (HSV type-1 or HSV type-2). For this reason, IgM testing is not recommended as a differential diagnostic tool, but may offer information about a particular patient’s antibody response.



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Links & References

The following websites and support materials are provided as a convenient resource only and should not be considered a complete list.  The information contained in these websites is neither endorsed nor controlled by Focus Diagnostics.

Websites

American Herpes Foundation
www.herpes-foundation.org

The website of the American Herpes foundation (AHF), a non-profit organization committed to improving the management and prevention of herpes virus infections through research and education. The site contains both patient and physician information. The site is supported by educational grants from GlaxoSmithKline and Merck.

American Social Health Association (ASHA)
www.ashastd.org/hrc

This website for the American Social Health Association (ASHA), a non-profit organization dedicated to stopping sexually transmitted diseases and their harmful consequences to individuals, families, and community. The site provides information about support groups, the range of hotlines operated by ASHA, and STD news.

For more information, send a self-addressed, stamped envelope to:
National Herpes Resources Center
American Social Health Association
P.O. Box 1327
Research Triangle Park, NC 27709

Herpes Hotline
(919) 361-8488

Centers for Disease Control and Prevention:
http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm

The facts about herpes as presented by The Centers for Disease Control and Prevention (CDC), the recognized lead federal agency for protecting the health and safety of people at home and abroad.

Herpes Diagnosis
www.herpesdiagnosis.com

This website was designed by Drs. Lawrence Corey, Rhoda Ashley and Gray Davis. These 3 individuals have spent over 25 years working in the field of genital herpes and have been instrumental in the development of antiviral therapy for the disease as well as developing the current western blot and PCR based assays for diagnosing this infection.

International Herpes Management Forum (IHMF)
www.ihmf.com

The website for the International Herpes Management Forum (IHMF). The site provides information that can be downloaded and educational guidelines for doctors and patients on the management of herpes virus infection. The site offers global links on herpes management, listing of meetings, and a library of posters and slide presentations on herpes.

International Herpes Alliances
www.herpesalliance.org

The website for the International Herpes Alliance (IHA), a newly formed organization that aims to offer support and information to those with genital herpes, those helping to manage the disease, and national patient support groups worldwide. A non-profit association run by patients, medical professionals and support group leaders. Sponsored by educational grant from GlaxoSmithKline.

Novartis/FAMVIR
www.healthandhope.com
www.famvir.com
www.genitalherpes.com

A website of genital herpes resources information. Includes a game to tests herpes knowledge along with treatment information.

GlaxoSmithKline/VALTREX
www.herpeshelp.com
www.valtrex.com
www.gsk.com

Facts about genital herpes, cold sores, and varicella zoster virus. Sponsored by GlaxoSmithKline.

HealthCheck USA
www.healthcheckusa.com

Developed to assist in the prevention of disease by offering health screening services to the public. HealthCheck USA provides health awareness screening to customers throughout the USA by providing patients with direct access to testing services from the country's major fully accredited medical reference laboratories.

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Booklets

"Four Tough Questions about Genital Herpes in the US" from American Social Health Association, 2000

"A Clinicians Guide to Diagnosis and Treatment of Genital Herpes" from AMA, November 2002 (funded by GlaxoSmithKline)

"Genital Herpes" authored by Hunter Handsfield, MD, 2001, McGraw-Hill

"You May Think You Don’t See Herpes, but…You May Only see the Tip of the Iceberg", 2001 (funded by GlaxoSmithKline)

FDA Consumer Magazine, "Genital Herpes: A Hidden Epidemic", March-April 2002

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Scientific Papers

Inaccuracy of Certain Commercial Enzyme Immunoassays in Diagnosing Genital Infections With Herpes Simplex Virus Types 1 or 2”, by Rhoda Ashley Morrow, American Journal of Clinical Pathology, Vol. 120, No.6 (December 2003)

"Sorting Out the New HSV Type-Specific Antibody Tests", by Dr. Rhoda Ashley, PhD, Sexually Transmitted Infections, Vol. 77, p. 232-237( August 2001)

"Evaluation of Enzyme Immunoassay System for Measuring Herpes Simplex virus type-1 and type-2 Type Specific IgG Antibodies" by Harry Prince, PhD, Journal of Clinical Laboratory Analysis 14:13-16 (2000)

“Time Course of Seroconversion by HerpeSelect ELISA After Acquisiton of Genital Herpes Simplex Virus type-1 (HSV type-1) or HSV type-2, by Rhoda Ashley-Morrow, Sexually Transmitted Diseases, Vol. 30 No.4 pp 310-314 (April 2003)

"Reactivation of Genital Herpes Simplex Virus type-2 Infection in Asymptomatic Seropositive Persons", by Anna Wald, MD, New England Journal of Medicine, Vol. 342, Number 12; 844-850 (March 2000)

"Risk of Human Immunodefiency Virus Infection in Herpes Simplex Virus type-2 Seropositive Persons-A Meta Analysis", by Anna Wald, MD, The Journal of Infectious Diseases, 185: 45-52 (2002)

“Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes”, by Lawrence Corey,The New England Journal of Medicine, Vol. 350,No.1, pp 11-20 (Jan 2004)

"Underdiagnosis of Genital Herpes by Current Clinical and Viral-Isolation Procedures", by Laura A. Koutsky, PhD, The New England Journal of Medicine (1992)

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Additonal Scientific References for Herpes Simplex Virus

Index of Herpes Simplex Virus Scientific Literature References

Title

Primary Author

Publication / Congress

Pub. Date

HerpeSelect Reference

Development of Clinically Recognizable Genital Lesions among Women Previously Identified as Having "Asymptomatic" Herpes Simplex Virus type-2 Infection

A. Langenberg

American College of Physicians

1989

 

Strategies for the Prevention of Neonatal Infection with Herpes Simplex Virus: A Decision Analysis

M. D. Libman

Reviews of Infectious Diseases

1991

 

Underdiagnosis of Genital Herpes by Current Clinical and Viral-Isolation Procedures

Koutsky

The New England Journal of Medicine

1992

 

Highly Sensitive Enhanced Chemiluminescence Immunodetection Method for Herpes Simplex Virus type-2 Western Immunoblot

J. Dalessio

Journal of Clinical Microbiology

1992

 

Recurrence Rates in Genital Herpes after Symptomatic First-Episode Infection

J. Benedetti

American College of Physicians

1994

 

Type-specific Antibodies to HSV type-1 and -2: Review of Methodology

R. Ashley

Herpes

1998

X

Genital Herpes - How Much of a Public Health Problem?

Mindel

Sexually Transmittted Diseases

1998

X

Improving the Management of Perinatal HSV Infection

S. Kroon
RJ Whitley

IHMF - Poster

1998

 

Herpes Management and Prophylaxis

Barton

Sexually Transmittted Diseases

1998

 

Herpes Simplex Virus Infection in Pregnancy

J. Malkin

Herpes

1999

 

Whole Cell Lysate Enzyme Immunoassays vs. Recombinant Glycoprotein G2-Based Immunoassays for HSV type-2 Seroprevalence Studies

P. Garcia-Corbeira

Journal of Medical Virology

1999

 

Ability of a Rapid Serology Test to Detect Seroconversion to Herpes Simplex Virus type-2 Glycoprotein G Soon after Infection

Ashley

Journal of Clinical Microbiology

1999

 

Evaluation of Three Glycoprotein G2-Based Enzyme Immunoassays for Detection of Antibodies to Herpes Simplex Virus type-2 in Human Sera

Eis-Hubinger

Journal of Clinical Microbiology

1999

 

The Place of Serology in Diagnosis of Atypical Genital Herpes Simplex Virus Infections

Patels

8th EADV

1999

 

Genital Herpes: Review of the Epidemic and Potential Use of Type-Specific Serology

R. Ashley

Clinical Microbiology Reviews

1999

 

Herpes Simplex Virus type-1 and type-2 seroprevalence among pregnant women in the Netherlands

MA Gaytant

European Society of Clinical Virology

2000

X

Evaluation of an Enzyme Immunoassay System for Measuring Herpes Simplex Virus (HSV) type-1-Specific and HSV type-2-Specific IgG Antibodies

H. Prince

Journal of Clinical Laboratory Analysis

2000

X

Age-Specific Herpes Simplex Virus type-2 Seroprevalence in General Populations from North, Central and South America

NJ Robinson

ICID

2000

 

Herpes Serology for Dermatologists

Goldman

Arch Dermatology

2000

X

Herpes Simplex Virus type-2 Seroconversion Among Persons Seeking Voluntary Repeat HIV Testing, San Francisco, 1997-1999

Turner

 

2000

X

Reactivation of Genital Herpes Simplex Virus type-2 Infection in Asymptomatic Seropositive Persons

Wald

The New England Journal of Medicine

2000

 

HSV type-2 is a major risk factor for HIV infection among young women in Carletonville (South Africa)

B. Auvert

AIDS Congress, Durban 2000

2000

X

Genital Herpes and Public Health - Addressing a Global Problem

Corey & Handsfield

JAMA

2000

 

The incidence of Neonatal Herpes in The Netherlands

M. Gaytant

International Journal Medical Microbiology

2000

X

Risk of Human Immunodeficiency Virus Infection in Herpes Simplex Virus type-2-Seropositive Persons: A Meta-analysis

Wald

The Journal of Infection Diseases

2000

 

Population-based herpes simplex virus seroprevalence in seven countries

Jen Smith

International Journal of STD & AIDS

2001

X

Serological HSV type-2 associated with HIV acquisition/transmission in discordant couples and the general population: Rakai, Uganda

Gray

International Journal of STD & AIDS

2001

X

Use of a Glycoprotein G-Based Type-Specific Assay to Detect Antibodies to Herpes Simplex Virus type-2 Among Persons Attending Sexual Transmitted Disease Clinics

Whittington

Sexually Transmittted Diseases

2001

 

Multi-Centre Herpes Simplex Virus (HSV) Seroepidemiology Study

French

2001

X

Sorting out the new HSV type-specific antibody tests

Ashley

Sex Transm Inf

2001

X

Comparitive Performance of Herpes Simplex Virus type-2-Specific Serological Assays from Meridian and MRL Diagnostics

Ribes

Journal of Clinical Microbiology

2001

 

Effect of Condoms in Reducing the Transmission of Herpes Simplex Virus type-2 from Men to Women

Wald

JAMA

2001

 

Performance and Use of HSV Type Specific Serology Test Kits

Ashley

Herpes

2002

X

Detection of Herpes Simplex Virus type-2-Specific Immunoglobulin G Antibodies in African Sera by Using Recombinant gG2, Western Blot, and gG2 Inhibition

Hogrefe

Journal of Clinical Microbiology

2002

X

Efficiency of Reconstitution in Immunoglobulin G from Blood Specimens Dried on Filter paper and Utility in Herpes Simplex Virus Type-Specific Serology Screening

Hogrefe

Clinical and Diagnostic Laboratory Immunology

2002

X

Serological Testing for Herpes Simplex Virus (HSV) and HSV type-2 Infection

Wald

CID

2002

X

HSV type-2 Antibody Detection in African Sera - Comparison Between rgG2 ELISA and Western Blot

Hogrefe

ESCV

2002

X

HSV type-2 Antibody Detection in African Sera - Investigation of the Discordance between Recombinant gG2 (rgG2) ELISA and Western Blot

Hogrefe

ESCV

2002

X

Age-Specific Prevalence of Infection Herpes Virus Types 2 and 1: A Global Review

Jen Smith

The Journal of Infection Diseases

2002

 

A sero-epidemiological study of herpes virus type-1 and 2 infection in Israel

Isacsohn

Journal of Clinical Virology

2002

X

Evaluation of Confirmatory Strategies for the Detection of Type-Specific Antibodies against Herpes Simplex Virus type-2

Eing

Journal of Clinical Microbiology

2002

 

Performance of Two Commercial Glycoprotein G-Based Enzyme Immunoassays for Detecting Antibodies to Herpes Simplex Viruses 1 and 2 in Children and Young Adolescents

Leach

Clincial and Diagnostic Laboratory Immunology

2002

X

Prevalence of Herpes Simplex Virus type-2 Antibody in Cameroun

Eis-Hubinger

Sexually Transmittted Diseases

2002

 

The role of Serological screening in the management of genital herpes

Ballard

MedScover - Infectious Diseases

2002

 

Seroprevalence and Correlates of Herpes Simplex Virus type-2 Infection in Five Sexually Transmitted-Disease Clinics

Gottlieb

The Journal of Infection Diseases

2002

 

Antibodies to HSV type-1/HSV type-2 in CSF in HSV type-2 PCR positive patients

Koskiniemi

Scotland Virology Meeting

2002

X

The Changing Epidemiology of HSV type-1 and HSV type-2: Implications for serological Testing

Lafferty

IHMF

2002

 

A Prospective Study of Genital Herpes Simplex type-2 Infection in Human Immuno Deficiency Virus type-1 (HIV-1) - Seropositvie Women: Correlations with CD4 Cell Count and Plasma HIV-1 RNA Level

Wright

CID

2003

 

Strategies for the Prevention of Neonatal Infection with Herpes Simplex Virus: A Decision Analysis

Libman

Reviews of Infectious Diseases

1991

 

The Acquisition of Herpes Simplex Virus During Pregnancy

Z. Brown

The New England Journal of Medicine

1997

 

Herpes Simplex Virus type-2 - A Persistent Problem

A. Arvin, M.D.

The New England Journal of Medicine

1997

 

Board 126. Evaluation of 2 HSV Type-specific EIA Kits in Initial and Recurrent Genital Herpes by HSV type-1 And HSV type-2

K.P. Chan

Abstract presented at ICEID

2000

X

Evaluation of four commercial enzyme immunoassays for the detection of type-specific antibodies to herpes simplex virus types 1 and 2

Nordbo

ESCV

2000

 

Potential Benefits of a Serodiagnostic Test for Herpes Simplex Virus type-1 (HSV type-1) to Prevent Neonatal HSV type-1 Infection

Lipsitch

Sexually Transmittted Diseases

2001

 

HSV type-1 and HSV type-2 Seroprevalence Study in Estonia

Kibur

IHMF

2001

X

Evaluation of a fully automated glycoprotein G2 based assay for the detection of HSV type-2 specific IgG antibodies in serum and plasma

Groen

Journal of Clinical Virology

2002

 

Time Course of Seroconversion by HerpeSelect ELISA After Acquisition of Genital Herpes Simplex Virus type-1 (HSV type-1) or HSV type-2

Ashley-Morrow

Sexually Transmittted Diseases

2003

X

Effect of Serological Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant

Brown

JAMA

2003

 

Herpes simplex virus seroprevelance and risk factors in women

Smith

IHMF - Poster

2003

X

Longitudal Reliability of Focus Glycoprotein G-based Type-Specific Enzyme Immunoassays for Detection of Herpes Simplex Virus Types 1 and 2 in Women

Cherpes

Journal of Clinical Microbiology

2003

X

Neonatal HSV Infection: Time to Reconsider the Diagnostic Approach

Geretti

IHMF

2003

X