This is Part 4 of a series on the Embers study of Lyme disease in non-human primates. As described in Part 1 of the series, the Embers monkey research study posed three questions: one regarding treatment of early disseminated Lyme disease, one regarding treatment of late disseminated Lyme disease, and one regarding the ability of the C6 to accurately detect infection. This part of the blog series focuses on the last question, the accuracy of lab tests. Embers evaluated the C6 antibody test to see if its results accurately reflected active infection. It was believed that the C6 might permit researchers to determine whether treatment cleared infection. However, the study concludes: “Reliable procedures to determine that infection has been cleared from Lyme disease patients have not been established.” Moreover, the study demonstrated that the ability of the C6 to detect active infection generally was poor. Although the test detected infection in 100% of the inoculated monkeys at 4 months, after this period it failed to detect active infection in 60% of untreated monkeys in the study and in 100% of infected monkeys that received treatment.

All antibody lab tests, like the C6, are indirect measures of infection.  Rather than detecting the bacteria directly, they detect antibodies produced by the patient’s immune system to bacteria. When the patient’s immune response fails to detect infection, the antibodies that the lab tests measures are not produced.  This results in a negative lab test.

The Embers study compared the C6 antibody test with more direct measures of infection, including PCR, culture, immunofluorescence (visualization of spirochetes in inflammatory lesions), and something called xenodiagnosis.  (Xenodiagnosis allows uninfected ticks to feed on the monkey and then examines the ticks for Bb. The use of xenodiagnosis in humans in controversial.) The Embers study found that even when there was direct evidence of persistent infection found through invasive tissue sampling, the C6 blood test failed to detect it. This suggests that the C6 test should not be used for diagnosis since with the passage of time those who have the infection will test negative and anyone previously treated with antibiotics will test negative.

The researchers believed that the reason the C6 test became insensitive in the treated monkeys was that the number of spirochetes may have been reduced or had become a dormant form of bacteria that does not produce the antigens necessary for the C6 test to be accurate.  No explanation was offered for the insensitivity of the test on 50% of the non-treated monkeys.

The insensitivity of the C6 antibody test may apply to other antibody tests as well. This is important because it may explain why patients with persistent manifestations of Lyme disease often test negative on lab tests.  Embers suggests that patients may have persistent infection even if they test negative on an antibody lab test.

This is consistent with the fact that other commercial antibody lab tests in Lyme disease fail to detect disease roughly 50% of the time.  If lab tests are this insensitive–in fact, no better than a coin toss for diagnosing Lyme disease, they should not be required for diagnosis.  Yet, this is what the IDSA Lyme guidelines require.  The Embers study suggests that this requirement will leave many patients who have Lyme disease undiagnosed and untreated.

This article is part of a series of reviewing the Embers findings for treatment of chronic and early disseminated Lyme disease as well as the effectiveness of the C6 antibody test. You can find these other posts here:

Part 1–New study shows Lyme persists in monkeys

Part 2–Treatment and Persistence

Part 3–IDSA 28-day treatment protocol fails to clear infection

Part 4–Lab tests fail to detect Lyme disease

Part 5–Of mice and men and monkeys

Read the journal article here.

References:

Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE. 2012;7(1):e29914.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134

The LYME POLICY WONK blog is written by Lorraine Johnson, JD, MBA, who is the Chief Executive Officer of LymeDisease.org, formerly CALDA. Contact her at lbjohnson@lymedisease.org.