Discontinuation of Herpes Simplex Virus (HSV) IgM Testing

Transcript and References

Introduction

Hi, I’m Matt Binnicker, the Director of Clinical Virology and Vice Chair of Practice in the Department of Laboratory Medicine and Pathology at Mayo Clinic. In this month’s Hot Topic, Dr. Elli Theel will discuss the over utilization of IgM serologic testing for Herpes Simplex virus and the recommendation by multiple agencies, including the CDC and the Infectious Diseases Society of America, to avoid using this test for clinical decision making purposes. As a result of these recommendations and data generated at Mayo Clinic, Dr. Theel will summarize why HSV IgM testing will no longer be offered through Mayo Clinic Laboratories. I hope you enjoy this Hot Topic, and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patient’s health care.

Thank you for the introduction and thanks to all the listeners joining us today.

Disclosures

Before we start, just a note that I do not have any relevant disclosures to share with respect to this presentation.

Herpes Simplex Virus Types 1 and 2: The facts and stats

The focus for this Hot Topic is discontinuation of HSV IgM serologic testing at Mayo Clinic Laboratories. But before getting into why we are planning to do this, just some basic background on herpes simplex virus (HSV).

As most of you are aware, there are two serotypes of HSV, HSV-1, and HSV-2, and infection with HSV is not uncommon among the population, with the most recent National Health and Nutrition Examination Survey from the Department of Health and Human Services showing that among 14 to 49 year olds, 47.8% of them were seropositive for antibodies to HSV type 1, and nearly 12% were seropositive for IgG to HSV type 2.

Primary infection and secondary reactivation typically manifest clinically with painful blisters or sores at the site of infection. However, disseminated disease, including development of HSV encephalitis, can occur.

HSV transmission most frequently occurs through direct contact with a lesion or mucosal surface, or through mucosal contact with genital or oral secretions containing the virus. Vertical transmission from mom to baby can also occur perinatally.

While HSV-1 infections are most frequently associated with orolabial lesions, and HSV-2 infections are mostly genital in location, this paradigm is shifting, with an increase in genital HSV-1 infections, particularly among young adults.

Diagnostic Assays for Detection of HSV-1/HSV-2

When it comes to diagnostic assays, two are most frequently used, including detection of HSV DNA using molecular assays such as real-time PCR. This method is preferred for cases of acute or active disease and can be performed on a variety of different specimen types and sources as listed below, depending on patient presentation and clinical picture.

Serologic testing for detection of IgM- and/or IgG-class antibodies to HSV is also available. There are a number of factors important to consider and understand though, when it comes to serologic testing for HSV antibodies.

First, IgM antibodies typically become detectable about 10 to 21 days post infection, with IgG-class antibodies developing around the same time.

Also, IgM antibodies may persist for months following resolution of the initial infection, and may or may not develop during recurrent infection, whereas IgG will persist indefinitely.

Important to recognize also, is that while IgG assays are type specific, meaning that they can differentiate between HSV type 1 and HSV type 2, HSV IgM assays are not. IgM serologic assays are unable to distinguish between HSV type 1 vs. HSV type 2 infections, which may be important in certain clinical scenarios, including, for example, in pregnant women.

HSV-1/-2 Serology Utilization Recommendations

When it comes to HSV serologic testing, there are number of utilization recommendations that have been put forth by the CDC and other agencies.

First, type-specific HSV IgG testing may be useful in the following scenarios, including in patients with recurrent genital or atypical symptoms with negative HSV RT-PCR or culture results.

Also, it can be helpful in patients with only a clinical diagnosis of genital herpes or in patients whose partner has genital herpes. HSV IgG serology is also recommended for individuals presenting for an STD evaluation, and especially in those with multiple sex partners, in those with HIV infection, and in men who have sex with men who are at increased risk for HIV acquisition.

When it comes to when not to test for HSV antibodies, the CDC and others specifically state that the general population should not be screened for antibodies to HSV, and also, the focus of this Hot Topic, that HSV IgM tests should not be used.

Recommended HSV-1/-2 Serology Utilization Rules

More specifically, the recommendation against use of HSV IgM tests has been put forth by multiple agencies, including by the CDC in the current sexually transmitted diseases treatment guidelines and the American Academy of Pediatrics, and finally, HSV IgM use is discouraged by the recently published guide to utilization of the microbiology laboratory, a joint publication by the Infectious Diseases Society of America and the American Society for Microbiology.

HSV IgM Utilization at Mayo Clinic Laboratories (MCL)

Given these recommendations, we recently took an in-depth look at HSV IgM test utilization at Mayo Clinic Laboratories, and found that anywhere from 3,300 to 6,500 HSV IgM tests are performed each month.

Additionally, we performed a retrospective review of all HSV tests, both molecular and serologic, that were ordered through MCL between May and July of 2018. We found that in total, 22,683 tests for HSV were performed, and that amongst those, 20% were orders for either only HSV IgM or also included HSV IgM testing in addition to HSV IgG testing. Interestingly, HSV IgM testing was associated with only a 2.3% positivity rate, and among the patients that had both HSV IgM and HSV RT-PCR ordered, 50% of them were RT-PCR positive and HSV IgM negative.

Ultimately, we concluded that HSV IgM testing is over-utilized with negligible added value to patient care.

Discontinuation of HSV IgM Testing at MCL

Therefore, based on the CDC, IDSA, and AAP recommendations, and based on our internal utilization review, MCL will discontinue HSV IgM testing.

This obsoletion will lead to the discontinuation of the test codes listed below, including the HSV IgM stand-alone test and the HSV IgM/IgG panel. The type-specific HSV IgG test, however, will remain orderable.

This obsoletion will also lead to the discontinuation of the ToRCH IgM profile. Clinicians will be able to order the other components of this profile, including the Toxoplasma IgM and the CMV IgM assays individually.

References

1. McQuillan, G., et al., Prevalence of Herpes Simplex Virus Type 1 and Type 2 in Persons Aged 14-49: United States, 2015-2016. NCHS Data Brief, 2018(304): p. 1-8.
2. Workowski, K.A., et al., Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep, 2015. 64(RR-03): p. 1-137.
3. Morrow, R. and D. Friedrich, Performance of a novel test for IgM and IgG antibodies in subjects with culture-documented genital herpes simplex virus-1 or -2 infection. Clin Microbiol Infect, 2006. 12(5): p. 463-9.
4. American Academy of Pediatrics. Committee on Infectious Diseases, et al., Red book: 2018-2021 report of the Committee on Infectious Diseases. 31st edition. ed. 1 online resource.
5. Miller, M.J., et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Updated by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67(6):e1-e94
6. Jung, S. and Theel, E.S. Overutilization of IgM Serologic Assays for Herpes Simplex Virus. Accepted: Journal of Applied Laboratory Medicine

Questions?

Contact us: mcleducation@mayo.edu.