Lyme 2010-3
2010 Lyme Articles-3
17 March 2010
Minerva Med. 2010 Feb;101(1):1-7.
Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease.
Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L.
AIM: Although intravenous antibiotic therapy is recommended for neurologic Lyme disease, safety concerns have been raised about treatment beyond 30 days in patients with persistent neurologic symptoms. The goal of our study was to evaluate the safety of extended intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease.
METHODS: We enrolled 200 consecutive patients with significant neurologic symptoms and positive testing for Borrelia burgdorferi. Patients were treated with intravenous antibiotics using various intravascular devices (IVDs). Standard IVD care was administered to all patients, and monitoring for medication reactions and IVD complications was performed on a weekly basis.
RESULTS: The mean length of intravenous antibiotic treatment was 118 days (range, 7-750 days) representing 23,654 IVD-days. Seven patients (3.5%) experienced allergic reactions to the antibiotic medication, and two patients (1.0%) had gallbladder toxicity. IVD complications occurred in 15 patients (7.5%) representing an incidence of 0.63 per 1,000 IVD-days. The IVD problems occurred an average of 81 days after initiation of treatment (range, 7-240 days). There were six suspected line infections for an incidence of 0.25 per 1,000 IVD-days. Only one of the IVD infections was confirmed, and no resistant organisms were cultured from any patient. None of the IVD complications were fatal.
CONCLUSION: Prolonged intravenous antibiotic therapy is associated with low morbidity and no IVD-related mortality in patients referred for treatment of neurologic Lyme disease. With proper IVD care, the risk of extended antibiotic therapy in these patients appears to be low.
So Stricker finally got around to publishing this defense of LLMD practices: pump the patient full of antibiotics until the wallet is empty. I’m looking forward to picking through the full article—assuming I can lay my hands on this obscure Italian journal.
One thing I have noticed is the published PubMed abstract is different from the original abstract published in J. Invest. Med. 2008;56:190 Meeting Abstr. 261.
The current abstract mentions 200 patients. The original one lists 199. (Maybe one was hiding under the bed.) The current abstract lists 6 “suspected line infections.” The original lists three. Discrepancies aside, if you add up the adverse events you get 15% of the study population. Does that appear to be low risk? Well, like I said, it’ll be interesting to read through the entire work of art.
Couple of other points of interest. The authorship has changed. Lorraine Johnson—a lawyer for the California Lyme advocates group—is now listed as an author. What role could she possibly have played in an alleged clinical trial for chronic Lyme disease? Is she just padding her resume in case she ever goes looking for a job?
Another author is V.R. Savely, a nurse who was run out of Texas for her treatment of Lyme patients and the Internet version of delusional parasitosis, called Morgellons, and who now works for—wait for it--Stricker. Another author is from QMedRx, the “Lyme literate” home infusion company. Presumably, they paid for this study, which only adds to the overall suspicion about the merits and the purpose of this piece of clinical sleight-of-hand.
Finally, I’m eager to find out what antibiotics were pumped into these people for “7-750 days.” And, of course, it should be especially interesting to see what case definition Stricker used to enroll his cohort of 199 or 200 patients. What did he define as “chronic Lyme disease” and did any of his patients recover from it after “7-750 days” on antibiotics.
So at the moment, we have a trial of unknown quality allegedly showing the benefits (or at least safety) of long-term antibiotics for “chronic Lyme disease” conducted by:
people who believe in the routine use of long-term antibiotics for a syndrome called “chronic Lyme disease;” who belong to an organization (ILADS) whose sole purpose to promote such treatments; whose incomes are dependent on such patients and such treatments; and a company whose income is partly dependent on selling such treatments to Lyme patients and LLMDs; all led by a guy who “falsified data” and “selectively suppressed data that did not support his hypothesis, and reported consistently positive data whereas only one of four experiments had produced positive results.”
If the IDSA or some drug company like Pfizer or Merck tried to pass off some research like this, the Lyme activist community would be screaming bloody“conflicts of interest” and speed-dialing Blumenthal, the Lyme-obsessed A.G. in Connecticut. But…strangely…they are not. Why is that?
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Labels: ILADS, Lyme disease, Stricker
13 March 2010
I'm not likely to get hold of this entire article, but I really would like to read what from the abstract sounds like a sensible approach to Lyme disease in non-endemic states.
J Ark Med Soc. 2010 Feb;106(8):186-8.
A clinical review of Lyme disease in Arkansas.
Patil N, Bariola JR, Saccente M, Vyas KS, Bradsher RW Jr.
Lyme disease is the most common tick-borne disease in the northern hemisphere. Since it was first described more than 30 years ago, Lyme disease has generated a great deal of controversy.
Lyme disease is not endemic in Arkansas, and testing for Borrelia burgdorferi can lead to clinical confusion, unnecessary treatment and excess cost.
This article will present a brief review of Lyme disease, with an emphasis on what is known regarding Lyme disease in Arkansas.
Posted by Relative Risk at 09:47 0 comments Links to this post
Labels: Lyme disease
10 March 2010
Lyme Disease - Drug Pipeline Analysis and Market Forecasts to 2016.Tuesday, 09 March 2010.GlobalData estimated that the Lyme disease market was worth $2.2m in 2009. The major reason for the limited market revenues is that there is no approved drug for Lyme disease treatment. Antibiotics such as doxycycline, cefuroxime and amoxicillin are currently used off-label. The patent protection of all these antibiotics expired long ago and many generic versions of the antibiotics are available very cheaply.
In 2009, the annual cost of therapy for Lyme disease with antibiotics was $81.
Between 2001 and 2009, the Lyme disease market grew only at a CAGR of 6.1%. The late-stage pipeline for the Lyme disease market is very weak and is entirely made up of antibiotics that are currently used as off-label drugs. Therefore, even though these drugs will receive regulatory approval for the Lyme disease market, the entry of antibiotics is expected to have a negligible impact on the market in terms of sales value and volume. Overall, between 2009 and 2016, the Lyme disease market is expected to grow at a CAGR of only 4.8% to reach $3.1m by 2016.
GlobalData found that the current competition in the Lyme disease market is strong. The currently used antibiotics are effective against the disease. Antibiotics are normally used in the early stages of Lyme disease and the drugs effectively treat the disease with minimum side effects.
Antibiotics are prescribed to be taken orally or intravenously in patients with late stage persistent Lyme disease to treat symptoms such as early arthritis, skin rashes, joint problems, late nervous system problems, or heart problems. The majority of the early-stage patients treated with antibiotics never test positive for Lyme disease again. This indicates that the market is well served by antibiotics.
[snip]
GlobalData found that the Lyme disease market is well served by the currently available off-label treatment options. The antibiotics used in Lyme disease treatment effectively treat patients and the patient compliance rate for the drugs is high. However, unmet need still exists in the Lyme disease market in terms of safety and the lack of approved vaccines.
These unmet needs can be effectively addressed by vaccines that are effective and safe in treating the disease. Vaccines not only treat the patients who already have Lyme disease but also prevent normal people contracting the disease.
GlobalData expects that two vaccines will enter the Lyme disease market after 2016. The market entry of these vaccines will positively affect the market and the market will grow at a significantly faster pace compared to the present market growth rate.
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Posted by Relative Risk at 14:30 0 comments Links to this post
Labels: Lyme disease
09 February 2010
Posted February 8, 2010
Short-course therapy may be as effective as long-course therapy for patients with Lyme disease
Long-term survival rates without treatment failure for patients with Lyme disease treated with antibiotics were about 99%, regardless of the duration of therapy, according to results of a recent study.
Todd J. Kowalski, MD, of the section of infectious disease at the Gundersen Lutheran Health System in La Crosse, Wis., was involved with the retrospective cohort study and follow-up survey. “There seemed to be no benefit to using prolonged antimicrobial therapy to treat early Lyme disease,” he said. “Long-term outcomes of patients treated with 10 days of antimicrobial therapy were as good as those treated with longer courses of antibiotics.”
Kowalski said there were no differences in subjective complaints of joint and muscle aches, fatigue, difficulty sleeping or difficulties concentrating between patients treated with antibiotics for 10 or fewer days, 11 to 15 days or 16 or more days of antibiotics when patients were surveyed on average 4.5 years after diagnosis.
The study involved 607 patients diagnosed with early localized and early disseminated Lyme disease. The study was conducted from Jan. 1, 2000, through Dec. 31, 2004, in an area hyperendemic to the infection.
Results
Doxycycline therapy had been administered to 93% of the study patients.
Among the patients treated with doxycycline, 17% were treated for 10 or fewer days, 33% were treated for 11 to 15 days and 47% were treated for 16 or more days.
Two-year treatment failure-free survival rates were calculated:
99.0% among patients treated for less than or equal to 10 days.
98.9% among patients treated for 11 to 15 days.
99.2% among patients treated for greater than or equal to 16 days.
The researchers wrote that patients treated for 16 or more days had lower 36-item Short-Form Health Survey social functioning scores at follow-up. However, Kowalski said no other differences in those scores were observed.
“We also found that objective clinical evidence of treatment failure following treatment with appropriately targeted oral antimicrobial therapy was exceedingly rare,” Kowalski said.
Treatment failure criteria were met by 1% of patients (n=6). Clinical details for four of those patients suggested reinfection. One of those patients was treated with an inappropriate antibiotic and one developed a facial palsy early on in the treatment regimen.
The overall rate of reinfection was 4%.
Commentary
“There has been confusion and uncertainty among clinicians and patients about the appropriate duration of antibiotic therapy for early Lyme disease,” Kowalski said. “This study adds compelling data that refutes the idea that longer durations of antimicrobial therapy for early Lyme disease improves outcomes. Patient outcomes were essentially the same, no matter the duration of antimicrobial therapy received. We know that antibiotic use always comes with some level of risk in terms of side effects, adverse reactions and resistance. Thus, our study demonstrates that prolonged courses of antimicrobial therapy for early Lyme disease does not seem justified.”
He said the study demonstrated that objective treatment failure was rare. However, he noted that there was a 4% rate of reinfection with Borrelia burgdorferi.
Kowalski said the study was conducted in an area hyperendemic for Lyme disease, and the duration of study follow-up was longer than in many previous studies of the infection.
“The location of the study at least in part explains the relatively high reinfection rate,” he said. “However, it highlights the importance of educating patients about tick prevention measures.”
This article indicates that treatment failure is extremely rare in patients treated for either early Lyme disease (single erythema migrans), which accounts for about two-thirds of cases of Lyme disease, or early disseminated Lyme disease, which accounts for more than 20% of cases of Lyme disease in the United States. Furthermore, patients treated with a relatively short course of antibiotics (<10 days) had outcomes similar to those of patients treated with longer courses of antibiotics.
This is consistent with laboratory studies of Borrelia burgdorferi, the bacterium that causes Lyme disease, which demonstrate that this bacterium is extremely susceptible to antibiotics. It is also consistent with another study by Gary Wormser, MD, that showed that patients with erythema migrans can be treated effectively with 10 days of an antibiotic.
Of course, most patients who received <10 days of treatment in the study by Kowalski had early localized Lyme disease, and it might not be valid to conclude that 10 days of treatment is equally effective for patients with early disseminated Lyme disease.
The most important conclusion is that virtually all of the patients were treated effectively with a single course of treatment, and that the few "treatment failures" actually either had a new infection from a subsequent tick bite or had not received proper treatment initially.
-Eugene D. Shapiro, MD
Infectious Disease News Editorial Board member
Kowalski TJ et al. Clin Infect Dis. 2010;50:512-520.
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Posted by Relative Risk at 07:56 0 comments Links to this post
Labels: Lyme disease
27 January 2010
Preface from: Borrelia: Molecular Biology, Host Interaction and Pathogenesis
Publisher: Caister Academic Press
Editor: D. Scott Samuels and Justin D. Radolf
Publication date: March 2010
ISBN: 978-1-904455-58-5
From the Preface:
Since the discovery of Borrelia burgdorferi, the Lyme disease spirochete, borreliology has evolved from a microbiological curiosity to a major branch of bacterial pathogenesis research. The rapid expansion of our field has been fueled by the continual emergence ("metamorphosis" might be a better word) of Lyme disease as a global public health problem; indeed, few infectious diseases have garnered more sustained attention from the scientific and, notably, the lay media. The Federal government and numerous private foundations have marshaled considerable resources to combat this illness on both the basic scientific and clinical fronts. These monies have not been wasted: our knowledge of the disease and its causative agent has grown exponentially, a trend that continues despite constrained NIH budgets and dwindling paylines. This same period has also witnessed a resurgence of interest and, consequently, scientific advancement in relapsing fever, the other major human disease caused by borrelia species, the agents of which have long been known for their uncanny ability to alter their surface antigen profile.
We, the editors, believe that the field of borreliology was not just ripe for, but also in great need of, the comprehensive treatment that this book represents. Although other books have been written about Lyme disease, their focus generally has been clinical or epidemiological; this is the first volume, to our knowledge, with a nearly encyclopedic coverage of the microbiological, immunological, genetic, ecological, and epizootic facets of pathogenic borrelia. Borrelia: Molecular Biology, Host Interaction and Pathogenesis coalesces and illuminates more than 25 years of tenacious study of the spirochetes that cause Lyme disease and relapsing fever. Our goal was to integrate the diverse aspects of our field toward a unified view of how these vector-borne, enzootic diseases have developed into such serious threats to humans. We are gratified that this project was embraced by numerous experts, some of whom participated in the dramatic events surrounding the discovery of the Lyme disease spirochete, one of the all-time great stories of medical sleuthing.
The field of Lyme disease research has been under assault from self-proclaimed "Lyme literati" that have used misinterpretations, misrepresentations, and bold fabrications to promote their ill-conceived and self-serving agenda regarding diagnosis and treatment. This book is intended to dispel accusations that scientists have conspired with their clinical colleagues to conceal from public view the "real truths" about Lyme disease and its etiologic agent. In so doing, we endeavor to emphasize that well controlled, carefully executed, and, above all, stringently peer-reviewed research is the only path to unraveling the mysteries of B. burgdorferi and its strategies for establishing persistence and inflicting damage on its incidental human host. In essence, this volume is, in part, a response to the repeated attacks on the purposes and integrity of scientists who have dedicated themselves to the study of this recalcitrant bacterium. Our objective is for this compendium to provide a foundation not only for further research progress, but also for sound policy decisions.
Unquestionably, there remains a substantial amount to learn about borrelia and their host interactions. Our field will maintain its present trajectory only if it continues to attract bright and passionate researchers. In addition to providing a much needed reference work for borreliologists and infectious disease specialists, we hope this book will explain the enigma of how these cunning bacteria have managed to hold so many of us in thrall for so long! We also hope, and expect, that the tangled web these spirochetes weave, as expounded in this book, will ensnare our successors.
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Posted by Relative Risk at 20:40 0 comments Links to this post
Labels: Lyme disease
25 January 2010
The Lyme Neuroborreliosis Program at New York University Langone Medical Center is a modern research and clinical facility founded with generous support from the Neurology Research Foundation, Inc. The program is interdisciplinary in scope, and translational in practice, assuring the flow of information from the brightest researchers in allied fields of medicine. Equally important, is the creation of a humanistic and compassionate medical environment for individuals battling Lyme disease.
Press Releases
"A new Lyme disease program led by neurologist David S. Younger will open its arms to chronically ill patients and their treating doctors, wielding science to get a handle on the disease. Younger and team will offer a service currently unavailable anywhere else in the world: collaborating with community doctors to treat infection that may be chronic, while at the same time reversing the neurological damage caused by an immune system gone awry." (Pamela Weintraub, Cure Unknown, Inside the Lyme Epidemic, 2nd Edition, 2009.)
Well, that didn't last too long. But then I suppose one Creationist-like center devoted to Lyme disease is enough for N.Y.
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Posted by Relative Risk at 22:23 0 comments Links to this post
Labels: Lyme disease, Quackery
24 January 2010
It’s been a busy week in LymeLand. There must have been some kind of nuthouse furlough recently because three Lymee wackjobs have just dumped a load of nonsense into the Internet, which in all fairness is basically what the 90% Internet is—a digital landfill for the mentally ill, the conspiracy-minded, the juvenile, and the criminal.First, former mental patient, Elena Cook, got hold of a computer long enough to post another “secret” report that Lyme disease is actually a bioweapon of some kind. Poor writing in the patent report below has led her to conclude that B. burgdorferi is a real weapon because it’s in a mixed list of potential biological weapons (e.g., B. anthracis, Y. pestis), common human pathogens (e.g., C. pneumniae, L. pneumophila) and generally harmless bacteria (e.g., E. coli, B. cereus). If she had been a little more careful in her reading (and a little less nutty), she might have noticed a paragraph in the document that said the technology would be useful for “hazardous bioagents OR the diagnosis of diseases in human patients"…like B. burgdorferi, a human pathogen that is not on the list of potential bioagents. Here’s the list.
AUTOMATED METHOD AND DEVICE FOR DNA ISOLATION, SEQUENCE DETERMINATION, AND IDENTIFICATION
Bacterial biological warfare bioagents capable of being detected by the present methods include, but are not limited to, Bacillus anthracis (anthrax), Yersinia pestis (pneumonic plague), Franciscella tularensis (tularemia), Brucella suis, Brucella abortus, Brucella melitensis (undulant fever), Burkholderia mallei (glanders), Burkholderia pseudomalleii (melioidosis), Salmonella typhi (typhoid fever), Rickettsia typhii (epidemic typhus), Rickettsia prowasekii (endemic typhus) and Coxiella burnetii (Q fever), Rhodobacter capsulatus, Chlamydia pneumoniae, Escherichia coli, Shigella dysenteriae, Shigella flexneri, Bacillus cereus, Clostridium botulinum, Coxiella burnetti, Pseudomonas aeruginosa, Legionella pneumophila, Borrelia burgdorferi (Lyme disease), and Vibrio cholerae.
The rapid identification of the nucleic acid sequences present in a complex biological sample has many practical applications. For example, the ability to rapidly identify the presence of pathogens in a biological sample, via their DNA or RNA signature, would be of enormous importance for the identification of hazardous bioagents or the diagnosis of disease in human patients.
Second, Tincup, a Maryland-based Lyme activist who seems to be the director of afictitious group called the Lyme Disease Education and Support Diseases of Maryland, has posted online a document called, “Maryland Lyme disease Fact Sheet 2009.” She got the wrong year for starters, then things completely fall apart. There are no facts in the document, and no references for those facts. Rather than pick it apart here, I sent a copy to the state health department with the suggestion that they pick it apart and provide correct facts and references in anticipation of some foolish resident reading Tincup’s missive and then calling the Department with questions or concerns.
Third, in response to a foolish question about a Lyme website called lymecryme, Tincup offered her opinion about the validity and accuracy of the site’s claims:
“In MY opinion...Most of the medical/scientific papers posted are actual science which can be found by doing a Pub-Med or extended search...”
So much for her opinion. The site is a mishmash of scientific terms and the delusions of a former Connecticut mental patient and convict, Kathleen Dickson. She’s a regular online ranter about everything from U.S. fiscal policy to Russia foreign policy to autoimmunity and pedophilia. Except as a case study for med students, I can’t imagine anyone paying attention to such a creature. Except maybe Tincup.
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Posted by Relative Risk at 15:34 0 comments Links to this post
Labels: Lyme disease, Psych
22 January 2010
Well, Lorraine Johnson has changed her blog photo but not her tune. Still playing fast and loose with the facts. Here’s her latest screech about antibiotic addiction among Lymees:While Lyme patients agree that managing these issues are important, we find that the IDSA overlooks the major cause of antibiotic resistance (the use of antibiotics in animals) and points to antibiotic resistance as an excuse for denying sick Lyme patients the treatment they need to restore their health. In addition, the IDSA does not emphasize the role of hospital hygiene (or the lack thereof) that fosters antibiotic resistant infections in hospitals. Hospital hygiene measures are unpopular with hospitals because they pose additional costs. Wow. That last sentence shows an amazing lack of knowledge and insight. Infection control is unpopular because of cost, but infections, prolonged illness, prolonged hospital stays, additional disease and death are not costly!? Huh?! For the less-than-clueless, I recommend reading Atul Gawande’s 2007 New Yorker article about the costs and consequences of basic hygiene and infection control practices. You can find the articlehere.As for the IDSA overlooking hospital infection control practices or the agricultural uses of antibiotics, one need only glance through the IDSA reports and testimony on antibiotic resistance. Not only do they make recommendations about nosocomial and agriculture issues, they also point out the growing problems of community-acquired resistant infections. Here’s a snippet from: IDSA Testimony on Antimicrobial Resistance at FDA Part 15 Hearing 04/28/2008 IDSA testifies at FDA hearing on antimicrobial resistance and makes twelve recommendations on appropriate FDA actions to help lead federal efforts to combat this growing problem.
Although primarily affecting ill people in hospitals, a growing number of the victims of drug-resistant bacteria, such as MRSA, are people in the community and outside hospitals, including healthy athletes and children. A recent study in the Journal of the American Medical Association (October 17, 2007) demonstrates that more than 94,000 people are infected and nearly 19,000 die annually from MRSA alone around the country – more deaths than those caused by emphysema, HIV/AIDS, Parkinson’s disease and homicide.
And, Recommendation # 6 FDA’s Center For Veterinary Medicine Should Move Quickly To Issue Its Long-Delayed Draft Regulation And Guidance #146 On Collection Of Data On Antibacterial Use In Animals.
And then there’s the IDSA’s excellent report, “Bad Bugs, No Drugs”: About 2 million people acquire bacterial infections in U.S. hospitals each year, and 90,000 die as a result. About 70 percent of those infections are resistant to at least one drug. The trends toward increasing numbers of infection and increasing drug resistance show no sign of abating.
A multi-pronged approach is essential to limit the impact of antibiotic resistance on patients and public health. Good antibiotic stewardship, infection control and prevention efforts, increased surveillance, and limits on agricultural uses of antibiotics are extremely important. But a more pressing concern is that, as the number of resistant pathogens continues to grow, the pipeline of antibiotics used to treat these “bad bugs” is quickly drying up.
So antibiotic addiction among Lymees is a problem, but it’s just a drop in the bucket of worldwide antimicrobial resistance among human pathogens and commensals.
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Posted by Relative Risk at 10:23 0 comments Links to this post
Labels: Lyme disease
19 January 2010
Family crusades against disease
By Maxine Hunter
Published: Monday, January 18, 2010
The Lee and Kelly Nanney family of Germantown are on a personal crusade to bring the dangers of lyme disease to everyone’s attention.
Their children, Wilson and Shelby Nanney, both students at Germantown High School, have been in a two-year battle with this disease and still have a way to go. Last year the family had to move to Kansas City, Kansas for seven months to a doctor who used I.V. antibiotics to treat the disease. There the teenagers received daily I.V. infusions through a picc line. “This treatment was five hours a day, seven days a week with hardly a break in between, costing our family upwards of $200,000.00,” Kelly Nanney said. “They are much better and we feel as if we may finally be
looking at calmer days ahead.”
$20K for a Lyme infection!? Hope they didn't take the kids here or here or here.
[snip]
For this reason, Kelly points out, Lyme disease awareness has to begin with the patient. “When it comes to lyme disease the Infectious Disease society of America gets an F,” she says. “The guidelines for lyme disease are under scrutiny at this time and there is supposed to be an answer by the end of the year as to whether they will be rewritten to help the patients, not the insurance companies.”
I wonder where these foolish people got this idea about the IDSA. Wacky Lyme activists and their money-grubbing LLMDS perhaps??
Posted by Relative Risk at 13:20 0 comments Links to this post
Labels: Lyme disease, Quackery
16 January 2010
CID 2010:50 (15 February)
Antibiotic Treatment Duration and Long-Term Outcomes of Patients with Early Lyme Disease from a Lyme Disease–Hyperendemic Area
Todd J. Kowalski, Sujatha Tata, Wendy Berth, Michelle A. Mathiason, and William A. Agger.
Section of Infectious Disease and Departments of Medical Education and Research, Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin.
From the paper's conclusions:
The optimal antibiotic treatment for early Lyme disease continues to be controversial for some physicians and the public at large. We sought to assess the long-term outcomes of patients with well-defined early localized and early disseminated Lyme disease by duration of antibiotic treatment in an area of Lyme hyperendemnicity. This clinical outcome study, which is to our knowledge the largest reported series of patients with early localized and early disseminated Lyme disease, suggests no difference in treatment failure rates or long-term health function among patients treated with targeted antibiotics for <10 days, 11–15 days, and >16 days.
Treatment failure as defined for this study was rare. Furthermore, although 6 patients met our predetermined criteria for treatment failure, 4 of these had ongoing tick exposure and periods of feeling well before redeveloping symptoms accompanied by objective evidence of disease; thus, these cases were more compatible with reinfection than with treatment failure.
One patient who developed treatment failure was treated with an ineffective antibiotic, which readily explains the “treatment failure.” Finally, 1 patient who met our definition of treatment failure developed seventh nerve palsy 12 days into a course of doxycycline therapy but no other clinical evidence of progressive disease. Progression of facial paralysis in the absence of any other clinical evidence of treatment failure is well described even in patients still receiving potent intravenous antibiotics and may well be related more to inflammation than to progressive infection. Taking these factors into account, our study provides strong evidence that persistent active infection with Lyme disease after appropriately targeted antibiotic against borreliosis is exceedingly rare, if it occurs at all.
Reinfection was much more common than treatment failure.
Subsequent infection with B. burgdorferi is a well-described phenomenon. In our cohort, 4% of patients developed subsequent infection with early Lyme disease, consistent with previous reports. This finding highlights the importance of counseling patients on the risk of subsequent infection with Lyme or other tickborne disease and instituting appropriate preventive measures, particularly in an area of Lyme hyperendemicity.
Such natural reoccurrences also highlight the difficulty of developing an effective Lyme vaccine, similar to syphilis infections in humans.
We defined possible treatment failure as being physician directed additional treatment for Lyme disease for subjective complaints in the absence of objective findings of persistent disease. This group of patients, as we have defined it, falls under the broad category of post–Lyme disease syndrome [4]. No convincing evidence has been reported that antibiotic therapy beyond the initial course provides benefit in this patient population.
Despite that, in our cohort, 6% of patients received additional antibiotics for these complaints. These patients had no objective evidence of persistent infection; it is likely that the subsequent treatment of these patients was unnecessary.
Antibiotic treatment guidelines for early Lyme disease were developed by our infectious disease physicians and used in our health system for many years, including the years encompassed by this study. The guidelines have consistently recommended a 10-day course of doxycycline for uncomplicated early Lyme disease. Thus, we anticipated that a relatively high percentage of patients with early Lyme disease would have treatment durations of <10 days; however, only 16% of patients were given <10 days of doxycycline treatment, whereas 44% of patients received >16 days of doxycycline treatment. This study supports short-course therapy with doxycycline.
We have observed, then, 2 interesting treatment patterns in our cohort.
First, despite treatment guidelines both locally in our health system and nationally that recommend short-course doxycycline for early Lyme disease, longer courses of therapy were routinely prescribed.
Second, despite a paucity of evidence for benefit and the certain attendant adverse effect risks, many physicians chose to treat patients again for Lyme disease based on persistent or recurrent subjective complaints. In our opinion, the use and misuse of antibiotics in this circumstance are not justified.
Reasons for physician nonadherence to the treatment guidelines were not studied; however, at our institution guideline nonadherence may be unique to treating Lyme disease. Group A streptococcal pharyngitis is another common infectious disease problem for which both our local health system and national guidelines are equally available to physicians. However, although 93% of pharyngitis patients are treated in accordance with local guidelines (internal data), only 19% of patients with early uncomplicated Lyme disease are so treated. On the basis of years of clinical conversations with patients and physicians, we speculate that both patients and physicians perceive a need for more prolonged courses of antibiotics to effectively treat both early and late Lyme disease. This study and others suggest otherwise.
[snip]
In conclusion, we have studied the long-term outcomes of a large cohort of patients with early Lyme disease and found no differences in outcome according to duration of antibiotic treatment. Future studies should try to identify reasons physicians prescribe prolonged antibiotics for patients with Lyme disease in the absence of peer-reviewed data and against the recommendations of local and national treatment guidelines.
[Note: It sounds like the personal beliefs of activists and their LLMDs are having an effect on the prescribing of antibiotics for Lyme disease. Perhaps that is not surprising after a decades-long campaign to promote the use of antibiotics to treat subjective complaints and good old-fashion hypochondria. And it’s good news for LLMDs and other quacks who can claim they are prescribing in a manner similar to the majority of private practice physicians. So how does one combat an urban legend like the treatment of Lyme?]
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Posted by Relative Risk at 11:37 0 comments Links to this post
Labels: Lyme disease
06 January 2010
From the UK's Health Protection Agency, which is in keeping with other European expert groups:
Background
There has been an increasing trend in recent years for some medical practitioners to make diagnoses of Lyme borreliosis unorthodox and unvalidated laboratory tests in patients who have a range of serious but non-specific symptoms. Many of these patients have not had any significant risk of exposure to ticks. The consequences of these mis-diagnoses have included recommendations for a range of inappropriate and potentially hazardous treatments, such as prolonged courses of parenteral cephalosporins and other antibiotics. In some cases, other medically significant causes of the patients’ symptoms were overlooked, and opportunities for appropriate treatment missed.
A report on these unorthodox and unvalidated laboratory tests was prepared by Professor Brian Duerden, Inspector of Microbiology and Infection Control, UK Department of Health.
[Cited references noted below may be found at the above web site.]
Unorthodox testing
There are a number of unorthodox tests available in certain commercial laboratories (mainly in the USA) that have been proven in independent studies not to be of value. One is the Lyme urinary antigen test (LUAT), which purports to detect B. burgdorferi antigens in urine from patients with suspected Lyme borreliosis. It is very unreliable, with a high incidence of false-positive results [2]. Claims have also been made for the QRIBb test, a rapid method using fluorescent microscopy to identify borreliae in blood and other fluids and tissues. This unvalidated test is highly unreliable and has no adequate scientific basis [3]. Other unreliable tests include the lymphocyte transformation test (LTT), and unorthodox applications and interpretations of immunoblots [4].
Seronegative Lyme borreliosis
Antibody tests are likely to be negative in the first few weeks of infection, but it is very uncommon for patients with late stage Lyme borreliosis to be seronegative. None of the features of later stage Lyme borreliosis is unique to the infection, and the patient’s history should be carefully re-evaluated for other diagnostic possibilities before a diagnosis of seronegative late-stage Lyme borreliosis is accepted [5,7]. Additional specialised antibody and PCR tests to look for evidence of B. burgdorferi infection may be helpful.
Post Lyme syndrome
A small percentage of patients may continue to have subjective symptoms after appropriate treatment, similar to chronic fatigue syndrome or fibromyalgia [6,7]. Their past treatment history should be reviewed and they should be carefully evaluated and re-treated if they have objective evidence of active infection. Other conditions, infectious and non-infectious, may also trigger similar symptoms [8]. A large American study showed that the frequency of pain and fatigue was no greater in patients who had had Lyme disease than in age-matched controls who had not had B. burgdorferi infection [6]. Another study showed that patients with post-Lyme syndrome who were re-treated with prolonged courses of antibiotics had similar outcomes to those who received placebo for the same duration [2]. Such patients are best treated symptomatically rather than with prolonged antibiotics, which can be associated with serious or life-threatening complications [8,9]. Other spirochaetal infections, such as leptospirosis, relapsing fever, and syphilis do not require prolonged or repeated course of antibiotics, and there is no scientific evidence to suggest that B. burgdorferi requires prolonged treatment.
Chronic Lyme Disease
Some fringe medical and other practitioners diagnose this condition in patients who have serious but nonspecific symptoms and no previous history to suggest Lyme borreliosis. Other patients diagnosed with “chronic Lyme disease” have had serious conditions such as motor neurone disease, Addison’s disease, and systemic lupus erythematosis (SLE), and they required very different types of treatment to those that had been recommended by the fringe practitioners concerned. Some practitioners use unorthodox tests as discussed above, and follow the guidance of a group whose website was shown to contain inaccurate information [10, 12]. Their guidelines are not supported by good quality scientific evidence and are likely to lead to a high rate of misdiagnosis. An international expert group recently reviewed issues related to the diagnosis and management of 'chronic Lyme disease' [13]. Patients are strongly recommended to seek advice from their own general practitioners and experts such as accredited infectious disease specialists before embarking on potentially hazardous and expensive treatments.
Information on the Internet
The web has a great deal of material on Lyme borreliosis, but extracting medically and scientifically valid information requires much more than casual browsing. Some websites give excellent information about Lyme borreliosis, others are grossly inaccurate, promoting potentially harmful unorthodox approaches to diagnosis and treatments. Much poor quality and potentially dangerous information is readily available on the internet [10,11,12]. The best all-round initial sources of information include the EUCALB website and the CDC’s home page on Lyme borreliosis [11,12].
Posted by Relative Risk at 17:19 0 comments Links to this post
Labels: diagnostics, Lyme disease
20 December 2009
Danbury Hospital readies Lyme registry
By Robert Miller, Staff Writer
December 18, 2009
DANBURY -- Take one Lyme disease case. Multiply that by a thousand, or more, and you may be able to glean some vital information about this complex disease from all the gathered information.
That's what Danbury Hospital plans to do, beginning early next year, when it opens its Lyme disease registry for the region.
But for it to work, the public must be willing to sign up.
"We really want to engage the Lyme community,'' said Dr. Ramin Ahmadi, the hospital's director of graduate medical education and research. "If the community supports it and participates in it, it will be wildly successful. If it doesn't, the project won't go very far.''
[snip]
Since then, Ahmadi said, the hospital has gone through all the complicated work that needed to be done to get an undertaking this complex off the ground. The hospital's own institutional review board, which rules on research projects, had to approve it. The project's leaders then had to find ways to link it with the hospital's electronic record system.
This work Ahmadi said, established the methods the project will use to protect the privacy and anonymity of the people who enter their case histories into the register.
[snip]
Ahmadi said the project will require that any patient involved with the registry have a doctor's certification that the patient has been diagnosed with Lyme disease.
However, the registry won't ask people to have a positive blood test for Lyme before joining the registry. For years, Lyme disease advocates have complained that because blood tests for Lyme can be inaccurate, depending on them as the sole diagnosis is highly unreliable.
Jennifer Reid of the Ridgefield Lyme Disease Task Force said requiring a doctor's report confirming Lyme disease is a good thing, since it relies on the observation of clinical symptoms, not just blood tests.
[This is where things begin to fall apart. Unless the registry contains actual cases and patient samples from current or prior infection the data will be a hodge-podge of misleading and probably useless information. It’s a case of “garbage in, garbage out.”]
Reid said the participation of the Lyme disease patients in the area, as well as advocacy groups, will depend on how well the hospital explains the objectives of the registry.
[ Good luck there. The Lymeland community has a long history of demanding more research and trials, but not actually coming forward to participate in those efforts. EvenFallon had trouble scaring up actual Lyme patients for his own NIH-funded trial.]
"What we all want to hear is how the registry will be designed,'' she said. "But we all understand the need for great research into tick-borne diseases. This is a very good opportunity to do that.''
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Posted by Relative Risk at 07:25 0 comments Links to this post
Labels: Lyme disease
17 December 2009
From a poster on the LymeNut Forum:
"I spent the better part of a day researching online and called the following doctors within 2 hours of NYC."
Dr Raxlen in NYC (a friend of ours went to him and did not have a positive experience though she did not elaborate)
- $900 initial fee + labs
- No insurance accepted
- No appts before Feb
Dr Leigner in Armonk, NY
- No insurance accepted
- Only nurse practitioners are seeing new patients
- $1065 for an initial 3 hr appt
- 2nd week of Jan availability
Dr Fein in West Caldwell, NJ
- Have not been able to speak to anyone
Dr Cameron in Mt Kisco, NY
- Accepts her insurance (HealthNet)
- Available appointment for next Monday.
Dr Streit in Howell, NJ
- do not take HealthNet (may take other insurance)
- Appts avail 2nd week of Jan
- $300 initial visit
Dr Horwitz in Hyde Park, NY
- No insurance accepted
- $975 for 2 hour initial consult
Dr Eiras in Jackson, NJ
- No insurance accepted, but they said testing is usually covered
- $300 new patient appt, followups $100-115
- No appts before Feb
The last time I saw a doctor it cost me $15.00.
Posted by Relative Risk at 13:52 0 comments Links to this post
Labels: Cameron, Lyme disease
16 December 2009
Antimicrob Agents Chemother. 2009 Dec 7.
Ineffectiveness of Tigecycline Against Persistent Borrelia burgdorferi.
Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.
An interesting--but complicated--paper about the persistence of borrelial infections in mice during and after antimicrobial treatments. Some of the paper’s important points are noted below. (Note: Tigecycline is a structural analog of minocycline that avoids tetracycline resistance mediated by…efflux…and ribosomal protection…)
Management of Lyme disease patients with antibiotics is based upon evidence based clinical guidelines.
[That’s the IDSA guidelines.]
What is not known is whether or not antibiotic treatment completely eradicates the infection….
[We do know more antibiotic treatments don’t help persisting symptoms.]
Antibiotics are likely to kill most B. burgdorferi organisms, but the immune system is needed to fully eliminate the remaining spirochetes. However, therein lies the challenge, since Borrelia burgdorferi has evolved to persistently infect fully immunocompetent hosts.
[Of course, this is true of most successful pathogens that have evolved over time. Until very recently, humanity had nothing else to rely on but a robust immune response. One lived or died depending on the genetic quality of that inherited immune system.]
These results challenge prevailing dogma about [the] effectiveness of antibiotics for eliminating B. burgdorferi infection….
[This is a critical point that Lyme activists and their enabling quacks are going to overlook because it runs counter to their personal and financial beliefs that more antibiotics are the key to treating so-called “chronic” Lyme disease. So much for the dogma of ILADS, the LDA, the CALDA, and other activist groups.]
Earlier studies on antibiotic treatment of laboratory mice that were based upon culture of tissues as a read-out, showed effective elimination of infection, and this was essentially confirmed with standard PCR assays. With the advent of more sensitive real-time PCR, PCR-positive, culture-negative evidence for spirochete persistence after antibiotic treatment has been increasingly recognized, using the mouse model….
[Yes, using the mouse: the natural host of this annoying little bug. Perhaps it’s not too surprising that the mouse (the host) and the borrelia (the parasite) would negotiate some kind of “immuno-pathogenic” compromise over time, allowing each other to exist and function without too much immunologic or pathogenic interference. The question is, have humans done the same thing or are we still sitting at the negotiating table hammering out boundaries of disease, inflammation, and stabilizing immunity.]
In the present study, tick transmission to SCID mice was confirmed, and spirochetes in the ticks survived molting into the adult tick stage. Furthermore, transmission of infectious spirochetes was shown to occur following transplant of tissues from antibiotic treated mice into SCID mice. The enhanced success of transplant-related infection in the current study was based upon observations that heart base and joint tissue were the most likely tissues to contain residual spirochetes….
[Interesting, but can it be done in fully immunocompetent mice?]
This parallels human clinical experience, in which treatment is generally more effective when administered during early Lyme disease.
[Again, this tends to be true of all infectious and non-infectious diseases You don‘t want to wait ‘til the last minute to treat TB or pancreatic cancer.]
…none of the samples tested from antibiotic-treated mice indicated transcription of flaB (flagellin), which is generally considered to be constitutively expressed by B. burgdorferi. The down-regulation of genes involved in nonessential functions, such as flagellin, has been noted in persistent forms of E. coli following antibiotic exposure.
[Well, there goes the activist conspiracy theory that no one is using the flagella antigen for diagnosis because it would show too many cases of Lyme disease and “chronic“ Lyme disease. A perfectly good conspiracy theory ruined by a little bit of genetic reality.]
Collectively, results from previous studies and the current study indicate persistence of low numbers of non-cultivable spirochetes, detected by real-time PCR, following antibiotic treatment. For at least 3 months after cessation of antibiotic, these non-cultivable forms can be acquired by ticks (xenodiagnosis), transmitted by ticks, survive the molts between larvae to nymphs to adults, infect recipient mice by tissue transplant, transcribe RNA, and express antigen in ticks and tissues in the form of morphologically identifiable spirochetes. The fact that these forms are unable to be cultured does not negate their viability.
It remains uncertain if non-cultivable spirochetes are present during the normal course of persistent infection, or if they are induced in response to antibiotic. Despite their persistence, previous studies and the current study indicate that antibiotic treatment results in a significant decline in antibody titers to B. burgdorferi suggesting that the persisting spirochetes remain sequestered or occult to immune surveillance.
The significance of antibiotic persisting B. burgdorferi has also been challenged, because no disease was evident in SCID mice infected with these organisms. That conclusion is not valid, since inflammation does not necessarily correlate with presence of spirochetes. Inflammation requires invasion of specific tissue types, such as synovium, and no inflammation is found in many other tissues (in fact the majority) infected with B. burgdorferi.
[So what’s driving post-infection/post-treatment inflammation and other symptoms?]
Tolerance to lethal concentrations of various antibiotics, even after prolonged treatment, has been observed in a wide variety of bacteria and clinical conditions. It is not clear whether these persisting forms of B. burgdorferi occur in human patients after treatment, or give rise to chronic disease later in life.
________________________
So we’re left with a lot of questions about the nature of “post-infection” or “post-treatment” pathologies associated with prior infection by B. burgdorferi. Not to mention the nature of persisting, non-cultivable borrelia themselves.
It would be helpful to do some of these same experiments on people. Fortunately, there’s a huge population of alleged “chronic” Lyme patients. Maybe some of them would like to volunteer for a little xenodiagnosis or donate some tissue samples? Probably not. They weren’t too eager to volunteer for antibiotic treatment trials (Science 1999;283(5407):1431). Hard to imagine many of them sitting still for biopsies and tick-feedings.
So questions persist…as do symptoms…and complaints…and conspiracy theories….so it’s back to the bench.
Posted by Relative Risk at 17:49 0 comments Links to this post
Labels: Lyme disease
30 November 2009
I keep reading these complicated imagining studies involving people who may have had Lyme disease, but it’s still hard to know what they mean or of what value they may be to the patient or the treating physician. It might be more interesting at this point to see what other infectious diseases patients (e.g., HIV, TBE, West Nile, EEE, Neisseria, CSD ) look like under SPECT.
And for all the complicated work, it doesn’t seem like the Lymees who funded this center and some of this work (below) are getting back what they hoped for. But then that’s science: favored opinions, hopes and beliefs ruined by uncooperative data.
Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy
Brian A. Fallon
(REPRINTED) ARCH GEN PSYCHIATRY/VOL 66 (NO. 5), MAY 2009
While most patients recover fully when treated with antibiotics soon after infection, patients who are treated months after the initial infection may sustain ongoing problems with fatigue, cognition, and pain despite receipt of a standard course of antibiotics. These patients have been described as having chronic Lyme Disease or post treatment Lyme disease syndrome.
The purpose of this study was to address the lack of systematic data regarding rCBFand rCMR in patients with persistent Lyme encephalopathy, a type of chronic Lyme disease characterized by cognitive deficits that persist or return after antibiotic treatment. In this study, carefully characterized patients were compared with age-, sex-, and education matched healthy volunteers (controls) using a series of PET scans in both resting and hypercapnic conditions to obtain full quantification of regional cerebral blook flow (rCBF) and regional cerebral metabolic Rate (rCMR) in the same subjects.
These patients reported that their cognitive symptoms emerged after contracting Lyme disease and that their symptoms either returned or persisted despite prior treatment.
…compared with controls, the patients had substantial differences in specific brain regions
of blood flow and metabolism.
…there was no evidence in this study that the patient group was characterized by an excess of extreme values.
Some of the dysfunction in neurologic Lyme disease may result from inflammatory changes in CNS blood vessels—a hypothesis supported by case reports of diffuse or focal vasculitides and strokes attributed to Lyme disease and by perivascular inflammation noted in brain biopsies of patients with Lyme disease.
…the patients and controls did not differ in global CBF during the hypercapnic assessment.
This study does not address whether the imaging abnormalities reflected persistent B burgdorferi infection as opposed to a postinfectious process. We also cannot prove that the imaging abnormalities might not be accounted for by another unexamined variable in which the groups differed.
….although patients reported developing cognitive problems only after getting Lyme disease, we cannot be certain that the identified brain regional abnormalities were not present prior to infection.
Although helpful in confirming objective central nervous system abnormalities in a patient with a history of Lyme disease, this pattern of hypofunction is nonspecific and cannot be used to make the diagnosis of Lyme encephalopathy.
In conclusion, this study demonstrates that patients with persistent encephalopathy after treatment for Lyme disease have objective neurobiological dysfunction.
Financed in part by: the Columbia University Lyme and Tick-borne Diseases Research Center established by Time for Lyme, Inc, and the Lyme Disease Association.
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Labels: diagnostics, Lyme disease
27 November 2009
A Tale of Two Spirochetes: Lyme Disease and Syphilis.
Halperin JJ.
Neurol Clin. 2010 Feb;28(1):277-291.
Two spirochetal infections hold fascinating positions in the history of infectious diseases. Numerous historic and literary figures were believed to have neurosyphilis, which consequently has been blamed for otherwise inexplicable developments in Western European history. More recently, Lyme disease has served as a focal point for the divide between evidence-based medicine and traditional experiential approaches, highlighting issues of physician autonomy in an era of guideline development, and epitomizing the tension between patient advocacy and scientific medical care.
Most significant is the societal context in which these diseases first appeared. Syphilis invaded Europe when biologic understanding of disease was limited. In the absence of knowledge of other diseases, and with few tools to diagnose syphilis unequivocally, all manner of clinical phenomena were blamed on this infection. Lyme disease was described at a time of far greater scientific understanding. However, the inaccurate notion that this is a novel infection for which diagnostic tools are limited, and the availability of the Internet to enable widespread but uncritical proliferation of information have contributed to an unfortunate degree of misunderstanding. At a time when the population is inadequately scientifically literate but simultaneously suspicious of organized medicine and sympathetic to populist outpourings, this has allowed the widespread acceptance of scientifically invalid information, culminating in state legislatures passing laws requiring insurance companies to pay for treatment that has been shown to be irrelevant, unhelpful, and, in fact, harmful.
Diagnosis
False-positives are a concern and fall into two groups. Some organisms, T pallidum, T denticola (an organism responsible for periodontal disease), and Borrelia responsible for relapsing fever, are so antigenically similar that differentiation can be difficult. Fortunately, little geographic overlap exists between relapsing fever and Lyme disease; syphilis can usually be differentiated using tests to measure reaginic antibodies, such as the venereal disease research laboratory (VDRL) or rapid plasma reagin (RPR) assays. These anticardiolipin antibodies are almost always produced in syphilis and are rarely if ever demonstrable in Lyme disease. More common is cross-reactivity caused by more global B-cell stimulation. Patients who have lupus, subacute bacterial endocarditis,12 parvovirus, and other disorders develop a significant polyclonal gammopathy that can result in cross-reactive false-positives on many serologic assays. This cross-reactivity can be most easily differentiated using a Western blot….
Clinical
Contrary to assertions of some internists and hapless candidates at the Neurology Board examination, Lyme disease does not cause every imaginable neurologic disorder.
Patients who have active Lyme infection, particularly with evidence of active inflammation such as arthritis, often experience ongoing fatigue and malaise, and perceive cognitive and memory difficulties. These symptoms are identical to the toxic metabolic encephalopathies seen in innumerable other chronic infections or inflammatory states.25 Unfortunately, some have asserted that these cognitive symptoms, in isolation, are strongly suggestive of Lyme disease, with or without laboratory support for the diagnosis. Because population studies indicate that these same symptoms occur for unexplained reasons in a significant number of individuals, even being sufficient to disrupt daily activities in a meaningful fashion in 2% of the otherwise healthy population,26 this assumption is clearly inappropriate.
Treatment
B burgdorferi is sensitive to common antibiotics; meaningful antimicrobial resistance has not been shown.7 For most patients, oral regimens with doxycycline, amoxicillin or cefuroxime axetil given for between 2 and 4 weeks are highly effective (grade A evidence). Numerous studies in the European literature indicate that oral treatment with doxycycline is highly effective (grade A evidence, meta-analysis) in individuals who have Lyme meningitis, cranial neuritis, and radiculitis.29 This treatment has not been tested in the United States but, in light of the known biology of the organism and its different strains, similar results seem likely.
SUMMARY
Because neurosyphilis and neuroborreliosis share similar biologic characteristics, these two spirochetal infections have several of the same distinct clinical themes. Both can readily seed the nervous system and cause prolonged infections, despite the presence of an obvious humoral immune response. Both are readily diagnosed primarily using serologic tests, which are excellent but imperfect. In both, CNS infection is most readily confirmed through CSF examination. Both infections remain readily responsive to straightforward antimicrobial regimens. However, each has acquired a distinct mystique, leading to its being blamed for a broad range of unrelated disorders. Hopefully the final common thread will be that, just as increased scientific understanding resulted in clarification of the true biology of syphilis, continued development of understanding of Lyme disease, and the dissemination and acceptance of this information, will similarly result in its demystification.
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Labels: Lyme disease
25 November 2009
Some notes from a recent paper on pregnancy outcomes should come as no surprise to many scientists, be a great relief to many pregnant women, and be dreadful news to Lyme activists who have used fantastic tales of child deaths and deformities to frighten the public.
Maternal Lyme borreliosis and pregnancy outcome
Andra Lakos, Norbert Solymosi
Int J Inf Dis, Nov 2009 (In Press)
With the exception of some publications, most early case reports have described patients with adverse outcomes following their pregnancies. Incidence and cross-sectional studies on populations of 1000–5000 pregnant women and/or their offspring found hardly any cases of Lyme borreliosis and, therefore, remained inconclusive with respect to risk for adverse pregnancy outcome.
The Center for Tick-borne Diseases, Budapest was opened in 1986 under the leadership of one of the authors (AL). Since then, 8149 erythema migrans (EM) patients have been seen, including 97 cases in which Borrelia burgdorferi s.l. infection was clinically evident during pregnancy. Here we report our experience with these cases.
From the 97 registered cases of gestational Lyme disease, we were able to analyze 95. Two women were lost to follow-up before delivery. All women were seen by the same examiner (AL). The following criteria for inclusion were used: (1) EM rash during pregnancy, as defined by the CDC and EUCALB criteria (n = 72). (2) Patients were included if they visited the center after delivery, with EM that had commenced before or during pregnancy (n = 17); in many of them the inflammation had already resolved at the time of the first visit to the center (n = 12). The condition for the inclusion of these latter patients was a definitive description of the EM made by the family doctor or another institute. (3) Those with clinically diagnosed acrodermatitis chronica atrophicans (ACA), with signs of inflammation still present15 after delivery, which had commenced before or during the pregnancy (n = 3) were included. (4) Patients with facial palsy beginning during pregnancy with preceding EM or with the presence of intrathecal Borrelia antibody production16 (n = 3) were also included.
The onset of the first clinical symptom (starting point) and the first day of the antibiotic treatment (end point) were used to calculate the length of the Borrelia infection during pregnancy.
We registered 23 adverse outcomes in 20 (21.1%) of the 95 offspring….
Our findings demonstrate a statistically significant association between untreated Lyme borreliosis and adverse pregnancy outcome. The association between the untreated Lyme borreliosis and first visit only after delivery was expected.
We should stress that adverse pregnancy outcome is a combination of several perinatal and neonatal indicators with different degrees of severity.
It appears that a specific syndrome representing ‘congenital Lyme borreliosis’ is unlikely.
However, spontaneous abortion, stillbirth, and preterm birth have frequently been identified in other published studies and were also found in our series.
We frequently observed hemangioma, a hitherto unpublished symptom coincidental with maternal Borrelia infection. In contrast, cardiac abnormalities were not found; these have been the most frequently published consequence of maternal Lyme borreliosis in other reports
It is striking that of the three pregnancies where the mothers had late Lyme borreliosis (i.e., ACA) and in which the infection was acquired long before conception and remained untreated before and during the whole period of pregnancy, none resulted in any fetal or newborn harm. Patients with late Lyme borreliosis, especially with ACA, always produce a strong antibody reaction against B. burgdorferi, while most EM patients usually have faint antibody titers. The intensive immune response of ACA patients may play a role in preventing Borrelia spread and transmission to the placenta or fetus.
Placentas and offspring were not tested for Borrelia by PCR or culture in our study. Therefore, it cannot be concluded that the adverse outcomes were a result of a Borrelia invasion of the fetus or placenta. The adverse outcome may have been a consequence of damage to the placenta or a maternal reaction to the infection. There are animal studies that have demonstrated maternal–fetal transmission but others have not supported this conclusion.
Ideally, a prospective, multicenter study should be conducted, enrolling sufficient numbers of women, in order to adequately address these research questions.
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Posted by Relative Risk at 13:20 0 comments Links to this post
Labels: Lyme disease
19 November 2009
Insciences.OrgPublished on 18 November 2009New Haven, Conn. — A protein found in the saliva of ticks helps protect mice from developing Lyme disease, Yale researchers have discovered. The findings, published in the November 19 issue of Cell Host & Microbe, may spur development of a new vaccine against infection from Lyme disease, which is spread through tick bites.Traditionally, vaccines have directly targeted specific pathogens. This is the first time that antibodies against a protein in the saliva of a pathogen’s transmitting agent (in this case, the tick) has been shown to confer immunity when administered protectively as a vaccine.The Lyme bacterium known as Borrelia burgdorferi is transmitted by ticks. When it moves through the tick, it is coated with a tick salivary protein known as Salp15. The Yale team injected Salp15 into healthy mice and found that it significantly protected them from getting Lyme disease. When combined with outer surface proteins of B. burgdorferi, the protection was even greater.
[snip]
Several years ago there was a Lyme vaccine on the market that utilized just the outer surface proteins of the bacteria. It was taken off the market in 2002, and to date no other antigen has been tested in phase III clinical trials.
The authors believe this new strategy of targeting the saliva - the “vector molecule” that a microbe requires to infect a host - may be applicable not just to Lyme disease but to other insect-borne pathogens that also cause human illness. “We believe that it is likely that many arthropod-borne infection agents of medical importance use vector proteins as they move to the mammalian host,” Fikrig explained. “If so, then this paradigm, described with the Lyme disease agent, is likely to be applicable to these illnesses. Currently, we are working to determine if this strategy is likely to be important for West Nile virus infection, dengue fever, and malaria, among other diseases.”
This isn’t a new idea—others have been working on a tick-based vaccine for a number of years—but it is a promising approach to the problem of protecting against multiple infectious agents carried by a single vector. You can develop half a dozen separate vaccines or develop one single vaccine against the vector itself. There is already one working model of such a vaccine: the Boophilus tick vaccine used to protect cattle in Cuba, Brazil and Australia.
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Posted by Relative Risk at 10:15 0 comments Links to this post
Labels: Lyme disease, vaccines
16 November 2009
ScienceDaily (Nov. 17, 2009) — Using a powerful microscopic live imaging technique, a research team led by Dr. Justin Radolf, professor in the Departments of Medicine and Genetics and Developmental Biology at the University of Connecticut Health Center, has discovered the way ticks transmit Lyme disease to humans is different than previously thought. The research is published online in the Journal of Clinical Investigation.
Radolf and researchers Star Dunham-Ems and Melissa Caimano tried a novel approach. They genetically modified a virulent strain of B. burgdorferi to express green fluorescent protein (GFP). "This bacterium glows and can be followed in the living state as it migrates through the tick to the mouse during feeding," explains Radolf. "Then using a powerful microscopic technique called confocal microscopy, we discovered that the transmission process unfolds quite differently than previously believed."
Spirochetes in culture are highly motile, and it is widely believed that during feeding, the spirochetes in the midgut rapidly move through the wall of the midgut. But Radolf and his team found that during much of the feeding period, the spirochetes do not move. They actually divide and surround the cells of the midgut lining or epithelium, forming tight networks. "We also found that the reason they don't move is that the tick midgut secretes molecules that actually inhibit the motility of the spirochetes," explains Radolf.
Eventually, spirochetes in the networks reach the base of the epithelium by completely surrounding the epithelial cells. At this point, they become motile, detach, and completely penetrate the midgut, although in very small numbers. These few bacteria then swim to the salivary glands, which they penetrate en route to the mouse. "So rather than being entirely motility-driven, dissemination of spirochetes within ticks actually happens in two phases," says Radolf, "which is something we didn't know before.
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Labels: Lyme disease
09 November 2009
Clinical Infectious Diseases 2009;49:1733–1735
BRIEF REPORT
Blood Cultures for Patients with Extracutaneous Manifestations of Lyme Disease in the United States
John Nowakowski, et al. Department of Medicine, Division of Infectious Diseases, New York Medical College
The findings of the present study document that spirochetemia can be detected in 20% of US patients with extracutaneous Lyme disease, including patients with neurologic, cardiac, or musculoskeletal manifestations. Positive blood culture results, however, were closely associated with having a concomitant erythema migrans skin lesion and with having a short duration of illness. Thus, the findings suggest that spirochetemia is principally found in patients with Lyme disease who have relatively early infection. These results are consistent with the observations made in studies involving rhesus monkeys in which positive blood culture results could only be detected for 6 weeks after inoculation of the spirochete. Similarly, in immunocompetent rodents, positive blood culture results are more frequently observed during the first 30 days after infection, although in certain strains of mice, spirochetemia has been detected in some animals at much later times (360 days).
[And from the “I’m shocked!” Department….]
Our findings are strikingly different from those of Phillips et al, [quacks from ILADS] who reported that B. burgdorferi was yielded by blood culture for 43 (91%) of 47 patients who had received or were receiving prolonged antibiotic therapy for putative “chronic Lyme disease.” Several follow-up studies, however, have been unable to reproduce the findings (without a single positive blood culture result). In fact, the novel culture medium used by Phillips et al was unable to support the growth of B. burgdorferi when the spirochete was directly introduced into it. [Probably all killed by that secret ingredient:Detroit tap water.]
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Labels: diagnostics, Lyme disease