James L. Schaller, M.D.  •  239-263-0133

Lyme Disease Testing Deficiencies

Ronald A. Hamlen, PhD

A central difficulty in diagnosis and treatment of Lyme disease, caused by the spirochete Borrelia burgdorferi, is the lack of a definitive and readily available laboratory tests for active infection. Without such tests it is difficult to determine who has the disease, the effectiveness of treatment, and the end point of treatment: a cure.

According to the National Institutes of Health National Institute of Allergy and Infectious Diseases (NIAID), the U.S. Centers for Disease Control (CDC), and the Food and Drug Administration (FDA), Lyme disease is a clinical diagnosis with laboratory results only useful as supporting data rather than the definitive data point for determining infection. These agencies have all acknowledged the commercially available serology or antibody tests, the ELISA and Western blot, are not sufficiently sensitive for diagnosis and warn of the over dependence on test results in diagnosis and treatment decisions.1-4

A number of researchers and clinicians question the appropriateness of the CDC tiered testing protocol and find the ELISA test to insensitive (several studies reported only 52-64% accurate) for identification of infection.5-8 However, even with the highly conservative CDC surveillance criteria, the CDC reports more than 20,000 new cases of Lyme disease each year.9,10

The issue of seronegativity, or active infection without production of detectable or identifiable antibodies, which are required with ELISA and Western-blot detection techniques, is significant and the subject of numerous published scientific papers.6,11-14 The heterogeneous nature of Borrelia burgdorferi can be highly challenging with laboratories using a single strain of this organism as not all strains produce the same antibody profiles.15-18 Negative serology is highly problematic for physicians who rely on test results to define a diagnosis.

Because of this lack of definitive test methodologies physicians must accurately and consistently diagnose early Borrelia burgdorferi infections based on clinical presentations: patient history, exposure risk, and symptoms. Supporting test data, especially for coinfections, e.g., Babesia, Ehrlichia, Bartonella, and Anaplasma, are useful.

The realization that with some individuals, Borrelia burgdorferi once entrenched, can be a persisting infection and emphasizes the need for early treatment and eradication before dissemination and intracellular infection has established. Treatment failures or relapses are reported with all current regimens, although they are less common with early aggressive treatment.19-21 The CDC states that late, complicated Lyme disease might respond slowly or incompletely, and more than one antibiotic treatment course can be required to eliminate active infection.22

The literature is incontrovertible that individuals with persistent symptoms had a longer period before treatment and a worse prognosis for cure than individuals without persistent symptoms.23,24

The conservative medical position argues that the majority of Lyme disease cases present with a bulls-eye rash (the erythema migrans) and a positive CDC two-tiered screening ELISA antibody test and confirmatory Western blot as defined by the restrictive surveillance CDC criteria. A number of researchers and clinicians question the definitive value of requiring a rash for diagnosis (based on several state health department statistics an EM rash was absence, unrecognized, or misdiagnosed in 41-65% of positive cases).25-27 Moreover, CDC surveillance criteria do not include neurologic nor chronic Lyme disease and these most serious forms of Lyme disease are overlooked by physicians depending on these criteria. Under these conditions, the diagnosis may be overlooked in up to 90% of cases.28

From the foregoing I hope you more fully understand the controversy in diagnosis and treatment of Lyme disease is rooted in uncertain science and flawed diagnostic tests and the heart of this uncertainty. The inappropriateness of treatment and insurance coverage denials, as well as physician disciplinary actions by a medical board based on the current state of testing science are inappropriate and damaging to patient care.

While all these issues lower the quality of care for Lyme disease patients, the most dangerous to our health is physician default to a Lyme disease diagnosis based on flawed laboratory testing.


I would like to express my sincere thanks for the hard work by Dr. Hamlen, it taking a hard topic and many articles, and boiling them down into an intelligent and readable format.

Dr. J


  1. CDC recommendations for test performance and interpretation from the second national conference on serologic diagnosis of lyme disease. MMWR 1995, 44: 590-91 www.cdc.gov/epo/mmwr/preview/mmwrhtml/00038469.htm
  2. Centers for Disease Control and Prevention (CDC). Case definition for infectious conditions under public health surveillance (Lyme disease surveillance case definition). MMWR 46 1997, (RR10): 1-55. wonder.cdc.gov/wonder/prevguid/m0047449/m0047449.asp
  3. FDA Medical Bulletin. 1999, Lyme Disease Test Kits: Potential for www.fda.gov/medbull/summer99/Lyme.html
  4. National Institute of Allergy and Infectious Diseases (National Institute of Health), Diagnosis of Lyme disease. www.niaid.nih.gov/dmid/lyme/diagnosis.htm
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