Supervillain or Drama Queen? Differentiation of Reinfection from Relapse in Recurrent Lyme Disease

Posted by John Staples • November 14th, 2012

Like a cinematic supervillain, Borellia burdorferi is sometimes portrayed as a big, bad boogeyman that’s vexingly difficult to kill. Proponents maintain that an episode of Lyme disease requires prolonged antibiotic treatment that lasts for months. Nonsense, says the Infectious Disease Society of America (IDSA): A standard course of treatment is adequate, and more elaborate or prolonged antibiotic prescriptions simply exposes patients to unnecessary treatment-related risks.

While the on-line debate about the management of Lyme disease is remarkably vitriolic, B. burgdoferi is no stranger to controversy. Practitioners offering unconventional approaches to Lyme disease are routinely reprimanded for being charlatans and quacks, while conspiracy theorists accuse the medical profession of corruption and cover-up. All of this acrimony has prompted numerous physician disciplinary hearings, countless magazine articles, an antitrust investigation of the IDSA, a feature-length film, and fodder for the recently-concluded American presidential campaign. Even if B. burgdorferi isn’t a supervillain, it certainly qualifies as a drama queen.

In this week’s NEJM, Dr. Robert B. Nadelman (New York Medical College, NY) and colleagues report on a clever study that tries to address the controversy surrounding treatment duration. They identified 17 patients with at least two bouts of culture-positive erythema migrans (EM) despite standard antibiotic treatment following each episode. The investigators then compared the B. burgdorferi genotype from each episode to determine if antibiotic failure and relapse was responsible for the recurrent EM.

How often was there evidence that it was the same bug coming back to haunt the patient again? The B. burgdorferi genotypes isolated from first and second bouts of EM were distinctly different for all of the 22 pairs of episodes examined. The investigators conclude that recurrent EM is almost certainly the result of a new tick bite and re-infection with B. burgdorferi and very unlikely to be the result of antibiotic failure leading to relapse of the previous infection.

In an accompanying editorial, Dr. Allen Steere (Massachusetts General Hospital, MA) notes the broader context in which the issue of relapse versus re-infection is set: Persistent B. burgdorferi infection has been hypothesized as a cause for medically unexplained symptoms that persist or arise soon after completion of a recommended antibiotic regimen. Considering this study and others, however, Dr. Steere concludes “the weight of the evidence is strongly against persistent infection as the explanation for persistent symptoms in antibiotic-treated patients with Lyme disease.”

This conclusion may not convince the patient advocates and unconventional practitioners on the other side of the debate. Like a supervillain, medical controversy can be surprisingly difficult to put to rest. Recurrence? Sequel? Whatever you call it, this is one argument that is certain to be in the limelight for years to come.

9 Responses to “Supervillain or Drama Queen? Differentiation of Reinfection from Relapse in Recurrent Lyme Disease”

  1. Carl Tuttle says:

    These researchers continue to focus on the acute or early stage of the disease while patients who are the sickest went years or decades before obtaining a diagnosis.

    This is yet additional propaganda to deny and ignore the late stage Lyme epidemic seen all across this nation.

    I fall under the category of patients who had a “prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease” as it took twelve years to obtain a diagnosis.

    Nadelman, Steere and Wormser should prove their theories that persistent infection does not exist by infecting themselves with the Borrelia spirochete (similar to Barry Marshall’s experiment) and forgo treatment for a year or so and then treat the infection following the recommended IDSA one size fits all protocol because after all, in their minds, this is little more than a nuisance disease.

    Sincerely,

    Carl Tuttle
    Hudson, NH 03051

  2. cave76 says:

    The researchers focus on the infection being caught early at which point a fairly short course of antibiotics will probably catch the infection in its early stage with good results. I totally agree with that theory.

    However, how many of us have ever been diagnosed OR treated right away?
    Many never even know they’ve been bitten by an infected tick.
    Only about 50% get that diagnostic bulls eye rash.
    Many can be infected but get no symptoms or only get those that are passed off as the flu or arthritis etc.

    But consider this scenario: You are bitten by a tick and suspect you might have Lyme disease. You call your doctor and perhaps have to wait several weeks for an appointment. Then, IF you’re lucky, he may perform a test for Lyme. Then you wait for that test results to come back. IF it’s positive you will then be given a short course of antibiotics.

    It’s been proven in mice in the laboratory that infection can reach the central nervous system within minutes to hours.

    So as you’re waiting for all those tests and appointments the infection will become FAR past early or acute. Tick Tock.

    But most of us won’t find a doctor who will even test for Lyme. I had to go to 15 different doctors to find one. Tick Tock.

  3. Tom says:

    The same researchers continue to waste valuable research $ with studies designed with severe confirmation bias aimed only at supporting their narrow minded beliefs and maintaining their reputations. They are afraid of designing studies to test the more important aspects of this disease. They are afraid to honestly explore seronegative patients. They treat the 1994 Dearborn 2 tiered protocol as though it was delivered by God. Virtually all studies are based on being “seropositive” which causes inclusion bias resulting in a self fulfilling prophecy. Seropositive, means one meets either the IGM or 5/10 IgG criteria. This criteria was found to be useless in Europe because of the strain and species diversity in Europe. The researchers also base their study designs on faulty assumptions such as the US NOT having strain or species diversity as in Europe. Studies by the biologists such as UCB’s Dr Lane have found both strain and species that cause human infection as in B. Bissettii. This suggests the US probably is like Europe in having more than one species and many strains of each. They have admitted recently that strain variation does effect the Blot test results but continue to ignore the discovery of more than one species in the US. Its crazy that other scientists don’t call them out. This is like an old boys club where the peer reviewers wink and nod and they just keep wasting taxpayers money.

  4. cave76 says:

    Since this blog is ‘for physicians’ how much faith would they put in a ‘clever’ study that included a mere 17 people??

    Furthermore—–there have been instances of recurring EMs
    PMID: 8436647
    “Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection.”
    It was deemed by these authors that reinfection was not believed to have reoccurred.

  5. J. Williams says:

       The article by Dr. Nadelman and co-workers (1) seems to be  scientifically sound, and unsurprising. There is true scientific consensus that prior exposure to Bb provides little protective immunity. Therefore people who live in moderately to highly endemic areas are always at risk of contracting a new Bb infection from tick exposure, whether or not they’ve been previously infected.

       Nadelman and coworkers have demonstrated re-infection has very likely occurred in the 17 patients they studied, who have had two or more episodes of sequential EM, each followed promptly by antibiotic treatment. I think everyone will agree that this is a common scenario in endemic areas. Unfortunately, the authors failed to provide information as to whether the new EM was located at the same skin site as the previous EM. Presumably it was not, further increasing the pre-test likelihood that these were new infections.

       The accompanying editorial (2) by Dr. Steere is not scientifically sound, in that It suggests an unwarrented connection between the story of these unsurprising reinfections, and the ongoing controversy over the adequacy of current diagnostic and treatment algorithms. Those who do NOT present with recognizable EM, usually face delayed or completely missed diagnosis and treatment for this rapidly disseminating infection, which is known to be well-adapted for avoiding immune clearance by the host.

       Early Lyme disease with EM which is promptly treated, whether or not it is a first case, has little relevance to late, disseminated Lyme disease, where the controversy is focused. Suggesting that Nadelman and coworkers’s article has any bearing on the controversy is misleading to physicians, and to members of the public who hear about it in the media.

    The “patient advocates and unconventional practitioners” will reject this spurious connection, and so should scientifically conscientious physicians.

    J. Williams
    Boston, MA

    1.  Differentiation of Reinfection from Relapse in Recurrent Lyme Disease.
    Nadelman RB, Hanincová K, Mukherjee P, Liveris D, Nowakowski J, McKenna D, Brisson D, Cooper D, Bittker S, Madison G, Holmgren D, Schwartz I, Wormser GP.
    N Engl J Med. 2012 Nov 15;367(20):1883-1890.
    PMID: 23150958
    2.  Reinfection versus Relapse in Lyme Disease.
    Steere AC.
    N Engl J Med. 2012 Nov 15;367(20):1950-1951.
    PMID: 23150963

  6. MrsKramer says:

    So are they saying that once one’s immune system has been impacted by Lyme disease, they are more likely to get it again upon new exposure to B. burgdorferi? How does this have anything to do with explaining the chronic illnesses being reported by thousands who have only had one exposure? This “clever study” seems to me to be using a flawed control group to form a desired, foregone conclusion – based on a nonsequitor of science.

  7. M. Ferrari says:

    Statistics don’t lie, as one of millions now infected with stealth pathogens I can assure you none of us are interested in having this debate linger. Steere should be in jail along with his cohorts and we will not rest until the ugly truth about these stealth pathogens and the ensuing cover up is revealed. Presenting Steere as an expert on stealth pathogens only allows this charade to continue, you should be ashamed and worried about your reputation as a trustworthy journal.

  8. Silvermaven says:

    Another Game Changer—
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057792
    Antigenic Variation engine of Borrelia burgdorferi.

    Link:
    http://www.plosone.org/article/info:doi … ne.0057792

    the number of Recombinatorial antigenic possibilities is enormous.

    Consider this new understanding

    and then ponder that

    the basis of all Antibody detection in North America [ELISA and WB kits}
    are based on manufacturing of kits from
    a
    STATIC SINGLE STRAIN of Borrelia burgdorferi,
    namely the B31 Strain

    which was isolated not from human kind
    but from

    a Tick resident of Shelter Island , Suffolk County,New York
    in the year 1981.

    How many Antigenic variations of Borrelia burgdorferi
    have been missed

    by use of this Static Single Strain, cloned
    for purity by limiting dilution to a single spirochete

    and then
    maintained in serial subcultures for 32 years?

    So when Serology is negative, does a Negative ELISA or Negative
    {less than CDC band count threshold for + WB by Guidelines}
    provide the patient and the physician with meaningful information.?

    NO it cannot because we know China is already reporting HUNDREDS of new strains.

  9. sc says:

    I’ve yet to verify this but a former RN here in Arkansas told me if a doctor reports a positive patient for Lyme disease. the state yanks or puts in jeopardy that physician’s license. Hence there are little or no medically documented cases of Lyme.

Leave a Reply

Please note: Comment moderation is enabled and may delay your comment. There is no need to resubmit your comment.

Submitting a comment indicates you have read and agreed to the Terms and Conditions.