Patterns and Associated Cost of Serologic Testing for Helicobacter pylori in the U.S. Military Health System

Mục Lục

Abstract

Introduction

Helicobacter pylori (H. pylori) infection affects about half of the world’s population and can lead to multiple complications if left untreated. Testing for H. pylori infection in appropriate patients with prompt treatment followed by the testing of eradication is the standard of care in the United States. Active Duty Service members (ADSMs) in the U.S. military are a unique patient population that may be at higher risk for acquiring H. pylori infection given frequent deployments to developing countries. Noninvasive diagnostic strategies include the urea breath test, the stool antigen test, and serologic testing, which include H. pylori immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) antibodies. Among noninvasive methods, the least sensitive is serology, and although there is clinical utility in testing for H. pylori IgG antibodies, H. pylori IgA or IgM antibodies have limited clinical utility. Despite this, H. pylori IgA and IgM antibodies are still widely ordered across the Military Health System.

Materials and Methods

In order to determine how frequently this testing is being ordered and the associated cost, we conducted a retrospective cross-sectional study of H. pylori serologic testing utilization in the MHS from October 2015 to September 2018 in adult patients using the MHS Data Repository. All H. pylori IgM, IgA, and IgG antibodies, H. pylori stool antigen tests, and H. pylori urea breath tests were queried during this time period across all ADSMs, retirees, and ADSM dependents for all adults. Cost information was obtained from LabCorp, and the institutional price used for cost analysis was the same throughout all military treatment facilities in the Department of Defense (DOD).

Results

We discovered that over a 3-yr period, 1,916 H. pylori IgA and 2,492 IgM antibodies were ordered. In total, the DOD spent close to $400,000 on antibody-based testing for H. pylori not accounting for indirect associated costs like personnel, supplies, repeat testing, as well as the costs of delayed diagnosis and associated complications.

Conclusion

H. pylori IgM and IgA have limited clinical utility, are inaccurate, and are costly to maintain, especially when more accurate alternative tests are available. Based on our analysis, we strongly recommend the removal of the H. pylori IgA and IgM serologic tests throughout the DOD in order to improve the efficiency and quality of care for patients suspected of having an H. pylori infection. Further research is needed to determine how these tests are ordered, how providers are responding to the results of the serologic tests, and if noninvasive testing is being ordered appropriately.

INTRODUCTION

Helicobacter pylori (H. pylori) infection is one of the most common infections worldwide; estimates show almost half of the global population has been colonized.1,2 Patients chronically infected or colonized, with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcer disease (PUD) and a 1 to 2% risk of developing gastric carcinoma.3,4,H. pylori infection is also associated with mucosa-associated lymphoid tissue lymphoma.3,5,6 Once diagnosed, H. pylori can be treated with a combination of antimicrobial agents and proton pump inhibitors.5 Active Duty Service members (ADSMs) in the U.S. military are at higher risk for infection compared with adults in developed countries because of frequent deployments to developing countries throughout the world.7 Without efficient diagnosis and treatment, unaddressed H. pylori infection can have serious long-term health effects.3 ADSMs use a considerable amount of nonsteroidal anti-inflammatory drugs (NSAIDs),8 and H. pylori infection increases the risk of NSAID-related gastrointestinal complications.1,9 This increased risk of complications directly impacts medical readiness. Testing is recommended in patients with active PUD, past history of PUD without documentation of prior cure of H. pylori infection, low-grade mucosa-associated lymphoid tissue lymphoma, history of endoscopic resection of early gastric cancer, uninvestigated dyspepsia with age less than 60 yr, long-term low-dose aspirin use, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura.1

There are many diagnostic modalities available for testing patients suspected of having H. pylori infection. Among them is serologic testing of H. pylori antibodies, which include immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) antibodies. Among the serologic tests, the most sensitive is the H. pylori IgG10, whereas the H. pylori IgM and IgA arguably have no substantial clinical utility.10–12H. pylori serologic testing for IgA and IgM is being used despite more accurate tests being available. We conducted a retrospective analysis of H. pylori serologic testing utilization across the Military Health System (MHS) from fiscal year October 2015 to September 2018 in adult patients in order to better quantify use and spending on low yield tests, which may complicate the diagnosis and treatment of H. pylori infections in the Department of Defense (DOD).

METHODS

We conducted a retrospective cross-sectional study using the MHS Data Repository from October 2015 to September 2018. The MHS Data Repository includes records of all TRICARE beneficiaries to include ADSMs, their dependents, and retirees across all military treatment facilities (MTF) in both inpatient and outpatient settings across the DOD. This data set did not include blood work conducted outside an MTF. All H. pylori IgM, IgA, and IgG antibodies, H. pylori stool antigen tests (SATs), and H. pylori urea breath tests (UBTs) were queried during this time period across all ADSMs, retirees, and ADSM dependents for all adults (≥18-yr-old). The test type and results were extracted for the above dates. Test totals were determined accounting for varying methods of ordering serologies to include various combination panels of IgM, IgA, and IgG. Cost information was obtained from LabCorp. The institutional price that was used for the cost analysis was the same price across all Military Treatment Facilities (MTFs) in the DOD.

This study was approved by the institutional review board at the Walter Reed National Military Medical Center.

RESULTS

From October 2015 to September 2018, 6,018 nonactive duty patients and 1,483 ADSMs had H. pylori testing performed in the MHS. There were 20,548 individual, unique tests; 362 were UBTs, 7,215 were SATs, and 12,971 were serologic H. pylori tests (Table I). Among the serologic tests, 1,546 H. pylori panels consisting of all 3 H. pylori immunoglobulins were ordered. There were 2,492 H. pylori IgM antibodies, and 1,916 H. pylori IgA antibodies ordered. Thus, 4,408 H. pylori IgM and IgA tests were ordered over a 3-yr period—approximately 21.5% of all H. pylori testing, not including gastric biopsies. In addition, 2750 patients of the 7501 (37%) who underwent testing had an IgA and/or an IgM ordered. The price of each H. pylori antibody test in the DOD is $30.01. In comparison, the price of each SAT is $50.52, and the price of UBT was $63.35. In total, the DOD spent approximately $389,919.93 on antibody-based testing for H. pylori IgA and IgM during the study period. This estimation only accounts for the direct charge for testing and does not include ancillary costs incurred with serological testing or costs associated with misdiagnosis or delays in care.

Table I

IgG

8,563

IgA 1,916 IgM 2,492 Total Ig 12,971 Stool Ag 7,215 UBT 362 Total tests 20,548 IgG

8,563

IgA 1,916 IgM 2,492 Total Ig 12,971 Stool Ag 7,215 UBT 362 Total tests 20,548
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Table I

IgG

8,563

IgA 1,916 IgM 2,492 Total Ig 12,971 Stool Ag 7,215 UBT 362 Total tests 20,548 IgG

8,563

IgA 1,916 IgM 2,492 Total Ig 12,971 Stool Ag 7,215 UBT 362 Total tests 20,548
Open in new tab

DISCUSSION

A common paradigm for the management of H. pylori is the “test and treat” model: testing for H. pylori infection and, if positive, starting treatment without resorting to a biopsy.13 The “gold-standard” for diagnosing H. pylori infection has been biopsy with histologic examination.3,6 UBT has a sensitivity of 95% and a specificity of 96%, and those of SATs are 95% and 94%, respectively.2 Serologic testing has a sensitivity from 85 to 92% and a specificity from 79 to 83%2; however, serologic testing cannot distinguish between active infection and prior exposure, so it cannot be used to confirm eradication.2,3,6,14 The H. pylori IgG is the only appropriate antibody test to use in patients with documented PUD and/or active bleeding given that H. pylori infection is a chronic infection.1,13 The IgM and IgA are rarely useful.10,12 The sensitivity and specificity of H. pylori IgG is 80 to 100% and 69 to 95%, respectively.15 The sensitivity of H. pylori IgM for adults, using SAT as the gold standard, is 4.4% and the specificity is 93.4%.10 IgM antibodies are only elevated in acute infections and can miss chronic H. pylori infections.16 Regarding H. pylori IgA, one comparison found that the sensitivity and specificity of IgG was 96 and 75%, respectively, and those of IgA were 81 and 79%, respectively.12 Another comparison reported the sensitivity and specificity of IgG as 92 and 84%, respectively, and those of IgA as 80 and 89%, respectively.17 Although the H. pylori IgA antibody detects chronic infections like IgG, it is not as accurate as the IgG given IgA antibodies are localized to the mucosa, which may allow for IgA antibody levels to under-detect the infection.12,16,H. pylori IgA antibody may be useful when ordered with the IgG antibody, as one study demonstrated that using both tests resulted in a positive predictive value of 95.7% and a negative predictive value of 97.7%, which are greater than each test by itself11. However, keeping the IgA antibody for this sole purpose retains the potential for misuse, because it assumes that providers across the MHS are aware of this synergistic effect. Clinical guidelines do not mention the utility of either IgM or IgA antibodies. Also, in the clinical setting, any discrepancy between the IgG and IgA tests would likely prompt the clinician to order more accurate tests like the SAT or UBT, which are readily available.

Although each antibody individually is less expensive than the UBT or SAT, often providers order all of the H. pylori antibodies, thus increasing the cost of testing. Our reported total cost is likely an underestimation. Further indirect costs include the time of the phlebotomists, basic supplies required for sampling, and costs and risks associated with delays in treatment for H. pylori or phlebitis associated with venipuncture for blood samples. When compared with other noninvasive tests, serologic tests can be misleading. As antibodies to H. pylori can remain detectable in the serum a long time after eradication, a positive H. pylori serology can be a false-positive resulting in unnecessary treatment in patients who no longer have active infection or who already completed eradication therapy.2,3,6,14 Because of the false-positive rates associated with the antibody-based tests, providers will usually check either a UBT or SAT in patients with a positive H. pylori antibody: there may be a double cost associated with providers ordering H. pylori serologies.

As the numbers show, over 20% of H. pylori testing consists of serology testing for IgA and IgM, and over a third of patients received IgA and/or IgM testing that was suboptimal and often misleading. If H. pylori IgM and IgA were removed as testing options, we posit that we would have more efficient testing with better diagnosis and timely treatment. By extension, we recommend that patients with suspected H. pylori infection should be ideally assessed with UBT or SAT and that serologic testing for H. pylori infection should be limited only to the IgG antibody.

In conclusion, H. pylori IgM and IgA have limited clinical utility, are inaccurate, and are costly to maintain, especially when more accurate alternatives are available. Based on the data collected and our analysis of the performance of the serologic tests, we strongly recommend the removal of the H. pylori IgM and IgA serologic tests throughout the MHS in order to improve the efficiency and quality of care for patients suspected of having an H. pylori infection as well as to reduce unnecessary spending in the DOD. Of note, the analysis presented does not factor behavioral responses of the providers ordering the tests; it only quantifies the number of the tests and cost associated. Research regarding whether or not the providers are ordering the aforementioned tests appropriately, how these providers are ordering serologic tests, and how they are responding to serologic test results require future investigations. In addition, it may be useful to determine the degree to which ADSMs are using NSAIDs chronically. Given the increased risk of ulcer complications in patients using long-term NSAIDs, current guidelines recommend that patients initiating long-term NSAID therapies should be tested for H. pylori infection1. NSAID use among ADSMs is widespread and knowing whether or not more individuals need to be tested for H. pylori based on the pattern of NSAID use further supports the need for efficient and streamlined diagnosis of H. pylori infection in the military8.

The views expressed in this manuscript are those of the author and do not reflect the official policy of the Department of Army, Navy, Air Force, Department of Defense, or U.S. Government.

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Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by US Government employees and is in the public domain in the US.

This work is written by US Government employees and is in the public domain in the US.