LYMEPOLICYWONK: Embers Monkey Trials Part 2: Chronic Lyme Disease Treatment and Persistence

14th February 2012


This is Part 2 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 my blog series on the Embers study focuses on the second question--the ability of 90 days of antibiotics to eradicate infection in late disseminated Lyme disease. The researchers defined late disseminated Lyme disease as 27 weeks after inoculation. Rhesus macaques were chosen as the animal model because they experience many of the key signs of human Lyme disease, including neuroborreliosis ( an infection of the brain or nervous system.)

Parallel Studies: The study was intentionally modeled after the 2001 NIH funded Klempner trial, which assessed the effectiveness of retreatment of patients with chronic Lyme with 30 days of IV Rocephin followed by 60 days of doxycycline. The Klempner trial looked at the SF-36 quality of life assessment and found the 90 day treatment protocol did not significantly improve patients’ scores.The treatment protocol in the Embers study was identical to Klempner but had the advantage of being able to use invasive tissues sampling to determine persistence—something which cannot be done in human subjects.

The idea of conducting a parallel study in monkeys so that actual persistence of infection could be determined through invasive tissue sampling was specifically proposed by the advisory committee to fact check the human results. (Carl Brenner of the National Research Fund for Tick-Borne Diseases and Phyllis Mervine, President of were both patient members of the Advisory Committee.) The hope was that the results of the two studies could be published at the same time. Unfortunately, for reasons unknown, the publication of the findings of monkey study–which contradict those of the Klempner study–was delayed for 11 years. (The Klempner study was funded in 1996 and completed in 2001; the portion of the Embers monkey study dealing with chronic Lyme was funded in 1998.)

Study Design: The chronic Lyme protocol in the Embers trial involved 24 monkeys, which were infected with Borrelia burgdorferi (Bb), and 4 control monkeys, which were not infected. Of the 24 infected monkeys, 12 were treated with antibiotics, 12 were not. One monkey in the antibiotic group of the study died of unrelated causes. Of the 4 uninfected control monkeys, 2 were treated with antibiotics and 2 were not.

The timeframe of the study involved infecting the monkeys with Bb, waiting 27 weeks, and then treating them for 90 days as in the Klempner study. Six months after treatment, intensive tissue sampling was conducted to determine whether Bb persisted notwithstanding treatment.

Results: 8 of 11 infected monkeys had persistent infection notwithstanding treatment. This means that for monkeys that go untreated for 4 months before antibiotic regimen begins, persistent infection after 90 days treatment is the norm. And it suggests that other treatment options should be explored.  These could include longer treatment durations like those used in other chronic infections such as tuberculosis (2 years), different antibiotics, combination antibiotics, and pulsed therapy.

The fact that the Klempner study and the Embers study conflict is important because the IDSA guidelines rely on the Klempner study to deny patients treatment for chronic Lyme disease. In its guidelines, the IDSA contends that the Klempner study showed antibiotic treatment was ineffective on patients with chronic Lyme disease. This contention relies on a premise that Embers proved false—namely that 90 days treatment with antibiotics would be sufficient to clear infection. The Embers study shows that this assumption is wrong. The infection persists even with 90 days of treatment. This suggests that rather than being ineffective as Klempner concludes 90 days of treatment may be insufficient to clear the infection.

Another important factor to keep in mind is that Klempner did not try to establish persistence through direct evidence from tissue testing, like Embers. Instead, the Klempner study attempted to measure effectiveness of antibiotic treatment on humans indirectly using the SF-36 quality of life survey and found that patient responses did not improve  after 90 days treatment.The Klempner study has been criticized because the sample size was too small to measure clinically relevant treatment effects. However, beyond this, if, like the monkeys, the patients had persistent infection after 90 days of treatment,  the treatment may not have been sufficient to improve patients’ quality of life.

The Klempner study went further though and concluded that there was no evidence of persistence based on negative blood PCR and blood culture—both regarded as highly insensitive (but non-invasive) methods to look for persistence. In contrast, the monkey trial relied on evidence from tissue samples. This contradiction underscores the importance of using animal models for research. The Embers method of demonstrating persistence, invasive tissue sampling, would be impossible to conduct on humans. In fact, this was the reason the parallel monkey trial was conducted.

Significant excerpts from the study:

Persistence: “Our results indicate that disseminated spirochetes of two different B. burgdorferi strains can persist in the primate host following high dose, or longlasting antibiotic therapy.”
. . . . “Our studies do however offer proof of the principle that intact spirochetes can persist in an incidental host comparable to humans, following antibiotic therapy.”
. . . . “Finally, the use of variable and pulse-dosing regimens of antibiotics may improve efficacy [43] and this warrants testing in an appropriate model.”

Mechanisms of Persistence: “The nature of the persistent organisms and the acquisition of tolerance to antibiotics are questions that need to be addressed. The B. burgdorferi spirochete is known to invade collagenous tissue as a possible mechanism of immune evasion.”
. . . .”The fact that organisms can persist in the presence of antibiotics such as penicillin and cephalosporins (ceftriaxone) that interfere with cell wall synthesis appears to stem from their ability to enter a dormant, non-dividing state [43,44], thus avoiding the need for cell wall synthesis to continue growth.”
. . . .”A ‘‘persister’’ phenotype may possibly be responsible for the recalcitrance of persisting spirochetes made evident by previous studies in mice and dogs [37,42,45], and by those presented in this report.”

This article is part of a series of blog posts reviewing the Embers findings for treatment of chronic and early disseminated Lyme disease as well as the effectiveness of the C6 antibody test. 

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 for this post:

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. Available at:

Klempner M, Hu L, Evans J, Schmid C, Johnson G, Trevino R, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. The New England journal of medicine. 2001 Jul 12;345(2):85-92.

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, formerly CALDA. Contact her at



3 thoughts on “LYMEPOLICYWONK: Embers Monkey Trials Part 2: Chronic Lyme Disease Treatment and Persistence

  1. I’ve been saying for years, after reading Kim Lewis’s work, that Lyme maybe caused by persistor cells and even many people in the Lyme community were skeptical.

  2. Since IV Rocephin followed with doxycycline p.o. was not effective, what IV antibiotic regimen do you recommend for chronic, disseminated Lyme?

  3. Who does the ALDF represent? The IDSA, insurance companies, and pharmaceuticals? Are they transparent? Where does their money come from?