New CDC/FDA Warning Against Unapproved Lyme Culture Test

Janis C. Kelly

April 18, 2014

Concerns about the purported Borrelia burgdorferi culture test marketed by Advanced Laboratory Services resulted this week in a blunt warning published in the Centers for Disease Control and Prevention's (CDC's) Morbidity and Mortality Weekly Report, advising use only of the 83 FDA-approved tests for diagnosis of Lyme disease.

"The Advanced Laboratory Services example highlights the problem of using tests that are unvalidated and not [US Food and Drug Administration (FDA)]-approved for diagnosing Lyme disease. We would caution clinicians and patients against the use of any unapproved tests," lead author Christina Nelson, MD, told Medscape Medical News. Dr. Nelson is from the CDC's Division of Vector-Borne Diseases, Fort Collins, Colorado. Study coauthors include Sally Hojvat, PhD, director of the FDA's Division of Microbiology Devices.

Dr. Nelson emphasized that for Lyme disease diagnosis, the CDC recommends a 2-step process of serologic testing: first, an FDA-cleared enzyme immunoassay, followed in immunoassay-positive or equivocal cases by confirmatory Western blot. Only patients positive on both tests are considered to have Lyme disease. B burgdorferi culture is notoriously difficult and recommended only in rare circumstances, primarily in research settings and for patients with early Lyme borreliosis, atypical rash, and no history of antibiotic treatment, which rapidly aborts culture positivity.

The Advanced Laboratory Services test, which costs patients $595, has been controversial since the company began marketing it in 2011. The marketing process exploits a loophole in US regulatory structure because it is a laboratory-developed or "home brew" test manufactured and used within a single laboratory, and so can be sold without FDA approval.

Concerns about the Advanced Laboratory Services blood culture led in August 2013 to a study by CDC researchers, led by Barbara J. B. Johnson, PhD, who concluded that 80% of the patient samples used to demonstrate the novel method of culturing Lyme disease spirochetes from serum contained gene sequences identical to those found in laboratory strains used to develop the test and were likely false-positives.

Almost simultaneous with the new warning this week came a rebuttal to the Johnson critique from Alan B. MacDonald, MD, from the University of New Haven, Connecticut, who argued that the Johnson analysis did not show contamination of the Advanced Laboratory Services Borrelia blood cultures because the gene sequences identified by the CDC were, in fact, not present in the tested human blood isolates.

Dr. Johnson replied that patient-related DNA sequences matched all 3 strains used as reference standards, that 80% of patient-associated DNA sequences matched controls over the region sequenced, and that despite commercial use for more than 2 years, this test has not been corroborated by an independent laboratory. Dr. Johnson concluded, "[W]e strongly recommend that patients and clinicians wait for independent verification of these findings before relying on results of this culture method to diagnose and treat patients."

Advanced Laboratory Services did not respond to a request for comment. The company Web site includes the following statement: "Advanced Laboratory Services is aware of the publication of the following article: Johnson BJ, Pilgard MA, Russell TM. Assessment of New Culture Method to Detect Borrelia species in Serum of Lyme Disease Patients. J Clin Microbiol. 2013 Aug 14. We intend to respond directly to the authors of that article and/or the journal concerning the findings in the article. We have no further comment and no one is authorized to comment on our behalf."

The authors have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. 2014;63;333. Full text


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