Discontinuation of Herpes Simplex virus (HSV) IgM Testing

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

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.

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.

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. 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. 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..

Join The 21 Day Challenge!

(WITHOUT Starving Herself And WITHOUT Doing Any Exercise
More Strenuous Than Walking To The Fridge!)

Watch Our Flat Belly Fix Video..