Rise in Lyme Cases Drives Interest in New Tests

Lyme disease is a growing problem in the United States. The disease is a tick-borne bacterial infection (Borrelia burgdorferi) that, if untreated, can have long-lasting rheumatic and neurological implications. But, early antibiotic treatment can effectively treat the infection and prevent progression of symptoms. Historically, definitive diagnosis has been complicated by reliance on antibody-based testing, which cannot determine if the infection was still active or not. But, with a surging number of cases, there is growing interest in the laboratory industry to improve diagnostic testing by turning to newer, more sensitive techniques.

The Centers for Disease Control and Prevention (CDC) reported last month that the number of geographic areas at risk for Lyme disease has substantially expanded over the past few decades, driven by climate change. Currently, the states with the highest disease concentration remain in the Northeast and upper Midwest, but cases of the disease are now spreading across the Mid-Atlantic. Lyme disease is the most commonly reported vector-borne illness in the United States and in 2013 it was the fifth most common nationally notifiable disease, with roughly 30,000 confirmed cases reported to the CDC annually. While CDC data shows the number of reported cases is steadily increasing, the agency says that the total number of people infected with Lyme disease is in excess of 350,000, or roughly 10 times higher than the yearly reported number. Poor diagnostic testing is partially to blame for this discrepancy.

A Snapshot of Current Testing
According to a September 2014 study published in Clinical Infectious Disease by CDC researchers, approximately 3.4 million tests are performed annually for Lyme disease at an estimated cost of $492 million. These estimates are generated from data provided by seven large commercial laboratories (ARUP, Clinical Laboratory Partners, Focus Diagnostics, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Specialty Laboratories), which accounted for greater than 76 percent of Lyme disease tests reported to health departments in endemic states in 2008.

Currently, clinical observations are used to diagnose patients with a history of probable exposure to infected ticks in the early weeks of symptoms (rash). According to the CDC, laboratory tests are "neither suggested nor required" to confirm diagnosis at this stage. However, for patients with musculoskeletal, neurologic, or cardiac symptoms, two-tiered serologic testing (an approved enzyme immunoassay [EIA] followed by an approved immunoblot/Western blot test, for confirmation of positive EIA tests) is recommended.

The Clinical Infectious Disease study found that in the large commercial laboratories, recommended two-tiered testing accounted for at least 62 percent of assays performed, standalone testing was conducted 38 percent of the time, while "alternative testing" accounted for less than 3 percent of assays.

Demand Drives New Testing Approaches
The CDC has vociferously warned against use of unapproved Lyme disease tests, but there is growing recognition of the shortcomings of current diagnostic strategies for the disease. In light of growing number of cases of suspected disease in broadening geographic areas and public awareness of the long-term impairments brought upon by untreated disease, interest is growing in tests that promise to identify active infection both earlier in the course of disease and in patients who remain symptomatic, despite negative diagnostic results or antibiotic treatment.

Current blood tests are referred to as indirect tests because they measure the body's immune response (antibodies) to Lyme disease infection, but not the bacteria itself. Further complicating current testing, antibodies remain detectable even after active infection is beaten. In active disease, the bacterium sheds very small pieces (antigens) that were previously beyond detection due to technological limitations.

Ceres Nanosciences (Manassas, Va.) is currently evaluating its Nanotrap Lyme Antigen Test in clinical trials. The test, developed in conjunction with George Mason University (Fairfax, Va.) utilizes nanotechnology to "trap" an antigen associated with Lyme disease from urine samples. The antigen is directly measured using Western Blot technology. The company says that the test marks an improvement in Lyme disease diagnosis, as the Lyme bacterial antigen can be detected within days of initial infection.

"The goal is to have a way to detect Lyme disease even before you make antibodies against it then you could treat the patient with antibiotics, and they wouldn't get all those terrible symptoms," says George Mason researcher Alessandra Luchini, Ph.D., in a statement. "Or, if someone has joint problems and they're convinced they have Lyme disease—and there are thousands of people who feel that way—it gives us a way to definitively say they do or don't have Lyme disease."

In addition to providing definitive information at two critical stages of disease, Ceres says the test could help improve antibiotic stewardship by avoiding unnecessary prescriptions in patients without active disease. The company says it raised $1 million within the last year to aid with commercialization of the test.

Earlier this year, T2 Biosystems (Lexington, Mass.) announced development of the T2Lyme Panel, in conjunction with Canon U.S. Life Sciences (Rockville, Md.). This test is being designed to identify the bacteria directly from a patient's blood, without the need for blood culture. The assay will run on the company's U.S. Food and Drug Administration-cleared magnetic resonance-based T2Dx platform. Michael A. Pfaller, M.D., T2 Biosystem's chief medical officer, tells DTET that while the assay is still in the "development" stage, the platform enables "very low limits of detection."

Takeaway: There is expanding commercial and public interest in emerging tests that can potentially improve the sensitivity of Lyme disease diagnostic testing. While tests may soon be entering the marketplace, it remains to be seen if evidence is strong enough to change testing recommendations.