Expires February 2021
With approximately 50% of the world population seropositive for antibodies to Helicobacter pylori, accurate identification is critical to identify patients who are suffering from gastric ulcers as a result of infection. Serologic detection of antibodies to H pylori will be discontinued March 1, 2016 at Mayo Medical Laboratories due to the poor performance characteristics of these assays and the recent lack of patient reimbursement from multiple large insurance providers. As alternatives to serologic testing, the urea breath test or stool antigen assay are recommended. This presentation reviews the clinical manifestations of H pylori infection, describes proper test utilization for diagnosis of H pylori and summarizes how the decision to discontinue serologic testing for H pylori was reached by Mayo Medical Laboratories.
Elitza Theel, Ph.D., Director of the Infectious Disease Serology Laboratory at Mayo Clinic in Rochester, Minnesota.
Presenter SlideWelcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice. Today we will review recent changes to the available non-invasive assays for diagnosis Helicobacter pylori infection.
Our speaker for this program is Dr. Elli Theel, Director of the Infectious Disease Serology Laboratory at Mayo Clinic, Rochester, Minnesota.
Dr. Theel, thank you for presenting today.Thank you for the introduction and to those of you listening to this presentation.
Of note, I have no relevant disclosures.
As you view this presentation, consider the following important points regarding testing for Helicobacter pylori infection. How is this test going to be used in your practice? When should the tests be used? How will results impact patient management?
The objectives for today’s presentation are to briefly review the clinical manifestations of Helicobacter pylori infection and to discuss appropriate test utilization for detection of this infectious organism.
Importantly, serologic testing will no longer be available through Mayo Medical Laboratories for antibody detection to H pylori. We will discuss why this testing has been discontinued and provide information on the alternative diagnostic assays available for diagnosis of H pylori infection.
So starting with the epidemiology of H pylori, seroprevalence studies estimate that roughly half of the world’s population is infected with or has been exposed to H pylori at some point in their life.
From unpublished data collected through Mayo Medical Laboratories, the seroprevalence rate for antibodies to H pylori among individuals in the United States varies from 17% to 34%, depending on the state of residence.
Regarding transmission of H pylori, it is important to remember that humans are in fact the primary reservoir for this bacterium and, also, that individuals will most likely remain colonized for life unless they are treated to eradicate the organism.
Person-to-person transmission most likely occurs through the fecal-oral route, though other, less-common or less well-described transmission routes exist, including oral-oral, or gastric-oral transmission, or through ingestion of contaminated water sources and, rarely, through zoonotic transmission.
With regards to clinical manifestation of disease, while acute gastritis likely occurs following infection, this is rarely diagnosed as the symptoms are typically self-limited and individuals rarely seek medical attention.
Without treatment, however, H pylori does establish a chronic infection, leading to chronic gastritis in almost all individuals. Roughly 85% of these chronic cases are entirely asymptomatic or present with only a mild gastritis. It is estimated, however, that a small proportion of these individuals, less than 1%, will eventually develop gastric mucosa-associated lymphoid tissue or MALT lymphoma.
In approximately 10% to 15% of individuals with chronic infection, H pylori will localize antrally in the stomach and among these individuals, approximately 20% are expected to develop a duodenal ulcer.
In the remaining 2% to 5% of individuals, H pylori will localize to the main body or corpus of the stomach and is associated with the development of gastric ulcers in roughly 10% of these patients.
Finally, a very small percentage of these individuals may develop gastric adenocarcinoma and due to its repeated link with malignancy, H pylori was classified as a group 1 human carcinogen by the World Health Organization (or WHO) in 1994 and remains the only bacterium that is classified as such.
Diagnostic Testing Options
So, for patients showing clinical manifestations of disease, how is H pylori detected? There are actually many different diagnostic testing methods available to help identify infection and they are generally categorized as either requiring invasive or noninvasive specimen collection procedures. While we will focus on noninvasive testing methods for today’s presentation, just as a reminder, invasive tests require endoscopy and biopsy of afflicted tissue, followed by evaluation of that tissue by histopathology, a rapid urease test and/or culture. While some H pylori molecular assays have been developed, these are not yet routinely available in clinical laboratories.
The noninvasive tests we will discuss today include the urea breath test, the stool antigen test, and serologic testing for detection of antibodies to H pylori.
Urea Breath Test
The first noninvasive test we will discuss is the Urea Breath Test, or as I will refer to it, the UBT. This is an in vivo test that takes advantage of the strong urease activity of H pylori. Briefly, the patient is asked to first submit a baseline breath sample, which simply involves breathing into a special bag, which I’ll show you shortly. Next they are asked to ingest C-13-labeled urea, and if H pylori is present in the stomach, the C-13-labeled urea will be converted to ammonia and C-13-labeled carbon dioxide, which will enter the blood stream and be carried to the lungs.
Shortly thereafter, the patient submits a postintake breath sample and the level of C-13-labeled carbon dioxide is compared between pre- and postbreath samples using a spectrophotometer as shown here with both the pre- and postbreath sample bags. This instrument measures the C13 levels in both samples and calculates the change in C13 levels over baseline, and for patients infected with H pylori, we would expect to see higher C13 levels.
The advantages of the UBT are many, including the fact that a positive result is definitive evidence of acute or active infection. This assay can also be used as both an initial diagnostic tool and as a measure of response to therapy to verify eradication, though the test of cure evaluation has to be performed at least 4 weeks following cessation of treatment. The assay is also FDA-cleared for individuals over the age of 3-years old and, perhaps most importantly, it is recommended by both the American College of Gastroenterologists and the American Gastroenterological Association as a first line tool for diagnosis of H pylori.
Limitations of the UBT include the need to discontinue antibiotics or proton pump inhibitors at least 2 weeks prior to testing as the test relies on an enzymatic reaction from live bacteria for accuracy. Also, the cost of this assay is higher compared to serology or stool antigen testing, though reimbursement is likewise higher for this assay.
Stool Antigen Test
The Helicobacter pylori stool antigen test is a standard ELISA design to detect H pylori antigen released from organisms lining the stomach wall. As antigen is only detected if H pylori is present, a key advantage of this assay, similar to the UBT, is that a positive result is evidence of active infection. Also similar to the UBT, the stool antigen test can be used as both an initial diagnostic tool and to establish cure posttreatment. There are FDA-cleared stool antigen assays available and similar to the UBT, the stool antigen test is recommended by both the ACG and AGA as a test of choice to establish active infection.
Among the disadvantages of this assay are the discomfort of sample collection and the need to discontinue both PPIs and antibiotics at least 2 weeks prior to testing to ensure H pylori viability and test accuracy.
The final noninvasive test we’ll discuss is serologic detection of IgM-, IgA- and IgG-class antibodies to H pylori. IgM- and IgA-class antibodies specific to this organism are detectable early on during acute infection and subsequently disappear, however, they can be transiently detected during chronic infection. With regards to IgG, it is detectable approximately 21 days following initial infection and remains elevated for years, despite eradication of the organism. Therefore, the utility of antibody detection for diagnosis of infection with H pylori is fairly limited.
However, some of the advantages attributed to serologic testing include the ease of specimen collection and the widespread availability and low cost, especially compared to the other noninvasive tests like the UBT.
The disadvantages of serologic testing, however, are many. First, their overall sensitivity and specificity are low for both acute and chronic H pylori infection compared to other noninvasive assays, and this will be discussed further on the next slide. Additionally, serology cannot be used to document eradication of H pylori posttreatment as IgG antibodies will remain detectable for months to years. There are also very few FDA-cleared assays available, and neither the ACG nor the AGA recommend their use as first-line tests for diagnosis.
And finally, due to all of these limitations, an increasing number of insurance providers are no longer providing reimbursement to patients tested for antibodies to H pylori.
Comparison of Performance Data
So, just to reinforce the lower performance characteristics associated with serologic testing for antibodies to H pylori compared to the urea breath test and the stool antigen test, this table shows the range of reported sensitivity and specificity values for detection of active infection by these 3 methods using culture as the gold standard. As you can see, serology reaches a sensitivity and specificity of almost 85%, compared to 95% or higher for the other 2 methods.
So based on these results, the ACG and AGA indicate that the urea breath test and stool antigen test are the preferred noninvasive assays for detection of H pylori and that only one or the other assay be used to evaluate a patient, not both. They also recommend that serologic testing be avoided, however, if it is used, all positive results should to be confirmed by a urea breath test or a stool antigen assay.
Therefore, based on the poor performance characteristics of serologic testing, the lack of support for the use of these assays by multiple gastroenterologic societies, and the recent cessation of reimbursement by insurance companies, Mayo Medical Laboratories will be discontinuing serologic testing for antibodies to H pylori on March 1st of 2016
As alternative to serologic testing, Mayo Medical Laboratories offers both the stool antigen test and the urea breath test for detection of active infection or for documentation of eradication. Also, should the need arise, culture and susceptibility testing of isolates is available.
In an effort to help guide clinicians and ordering practices, the algorithm for diagnosis of H pylori has been updated on the Mayo Medical Laboratories website.
In summary, we have discussed that though infection with Helicobacter pylori is largely asymptomatic, some individuals may develop more serious manifestations, which require diagnostic testing.
Among the noninvasive assays, serologic testing is no longer available through Mayo Medical Laboratories due to the poor performance characteristics of these assays, their lack of endorsement reputable gastroenterologic societies including the American Gastroenterological Association and the American College of Gastroenterology, and, finally, the lack of reimbursement from numerous insurance companies.
As alternative testing methodologies, we recommend the use of the urea breath test or the stool antigen test, both available through Mayo Medical Laboratories.