LymeNet Newsletter Volume 1 Issue 02

Volume: 1
Issue: 02
Date: 05-Feb-93

Table of Contents:

SCIENCE: Letter: LD: Asking the Right Questions, by Carl Brenner UPI: Deer Ticks Seem to Prefer Biting People Wearing Clothes LYME TIMES: Dr. Edwin Masters of Missouri vs. CDC QUESTION: How Accurate are LD Tests? QUESTION: What is the Prognosis for Chronic LD? QUESTION: LD in Med/Africa? COMMENTARY: Yale's Flawed Prophylaxis Study, by John O'Donnell BIBLIOGRAPHY: Listing of Several Interesting Publications

Newsletter:

***************************************************************************** * Lyme Disease Electronic Mail Network * * LymeNet Newsletter * ***************************************************************************** Volume 1 - Number 02 - 2/05/93

I. Introduction II. News from the wires III. Questions 'n' Answers IV. Op-Ed Section V. Partial Bibliography for Further Reading VI. Jargon Index VII. How to Subscribe, Contribute and Get Back Issues

I. ***** INTRODUCTION *****

The LymeNet has been in existence just two weeks, and the response has been overwhelming. We are starting to get subscriptions from LD researchers and physicians. Dr. David Dorward from the NIH's Rocky Mountain Labs is with us. He will share his thoughts on LD testing soon. In addition, Drs. C. DeMarco and J. Burrascano have indicated interest. Dr. DeMarco has confirmed that she will subscribe. Dr. Burrascano is still looking for the best way to get Internet mail. Dr. Jeffrey Lyons from the University of Minnesota has also joined our group.

I would like to be up front with you about the biases of this newsletter. As you know, there is no such thing as total objectivity. Even the best reporter brings some pre-conceived notions to the job. Thus, I want to share with you the assumptions I make when compiling this newsletter:

1. LD is an epidemic (some actually dispute this). 2. There is a subset of patients who do not recover with the currently recommended treatment protocols. The actual number of these patients is unknown. 3. With the currently available serological testing procedures, diagnosis is very difficult, often very subjective. Thus, misdiagnoses are not uncommon.

Now... on with this issue's material. From the Wires, we have a letter to the editor to Science Magazine by Carl Brenner about the V Int'l Conference on LD last May. Ralph Yozzo submitted the second item about ticks and clothing. It suggests that nudists are less likely to get bitten by ticks! I still wouldn't recommend hiking nude, though. :-)

The latest issue of The Lyme Times reports on the battle between Dr. Edwin Masters of Cape Giradeau, Missouri and Dr. David Dennis of the CDC. We will update you on who threw the latest punches. If any folks from Missouri have any further info on this conflict, please send it in.

In our Q&A section, we have some answers to submitted questions. You may still submit responses to the questions. I will print responses no matter how late they arrive (some parts of the Net are slower than others).

Finally, John Setel O'Donnell gives us his two cents on the issue of prophylactic treatment.

Keep those contributions coming!

-Marc.

A few notes: 1. The Lyme Disease Network of NJ's monthly support group meeting will take place next Monday, February 8 at 7:30 pm in the East Brunswick public library. Call 908-390-5027 for directions and further information. In you would like your support group meeting times posted, please send that info to LymeNet-L. 2. Lehigh University subscribers may easily print this newsletter if they are using the DOS version of Access. While reading this memo in your mailbox, hit F-4 (Download), and type prn as the destination filename. Then choose either kermit or FTP as the download protocol, and the newsletter will be printed to your local printer.

II. ***** NEWS FROM THE WIRES ******

SOURCE: Science Magazine ISSUE: Vol 257, September 25, 1992, p1845 [LETTERS THE EDITOR] HEADLINE: Lyme Disease: Asking the Right Questions

(Ed note: This letter appeared as a follow-up to an article reporting on the controversy at the Fifth Int'l Conference on LD. At that conference, the organizers tried to remove certain abstracts that allegedly lacked "scientific merit." Pressure from patient groups had the abstracts re-instated. The offending abstracts primarily dealt with issues of chronic infection.)

I would like to elaborate on some of the issues discussed in Marcia Baringa's article about the controversy at the Fifth International Conference on Lyme Borreliosis (News & Comment, June 5, p1384). The academic Lyme disease researchers would have us believe that there is a methodological conflict between their own studies and their clinician opponents' "anecdotal" findings. Nothing could be further from the truth. Although criticisms of the offending abstracts submitted before the conference were not entirely without merit, the presumption that the existing body of academic Lyme disease literature represents some sort of scientific ideal is ludicrous.

The central flaw in the current Lyme disease orthodoxy is the persistent myth of "post-Lyme syndrome." This condition was suggested by researchers to account for the troublesome fact that many patients do not fully recover after supposedly curative antibiotic therapy, but continue to suffer from chronic headaches, cognitive deficits, debilitating fatigue, and parenthesis. These persistent symptoms are explained away by the fibromyalgia syndrome [1], which provides a convenient sense of closure to researchers but leaves patients in the throes of devastating illness.

There is ample evidence to retire this model in favor of one involving chronic infection. Some researchers have successfully cultured Bb from the skin or cerebrospinal fluid of patients after antibiotic regimens generally accepted as curative by academic researchers [2], while other clinicians have recovered the bacteria from patients who have undergone even long-term high-dosage antibiotic therapy [3]. In addition, researchers have demonstrated that Bb can penetrate and persist within human endothelial cells [4] and fibroblasts [5]. Yet most academic researchers continue to deny the prevalence of chronic infection in Lyme disease.

There are also flaws with the academicians' diagnostic protocols. Lyme disease presents physicians with a diagnostic dilemma because its symptoms are so diverse and the commonly available serological tests used in diagnosis are known to be unreliable. Thus, while it may seem reasonable for researchers to insist that clinicians confine their studies of long-term therapy to patients who are demonstrably seropositive, it is scientifically -- and morally -- indefensible to advocate a rigid adherence to this overly restrictive diagnostic procedure in a clinical setting to determine treatment. Arbitrarily withholding antibiotic therapy from all seronegative patients guarantees that an unacceptably high percentage of them will go on to develop incurable late-stage Lyme disease. Such a policy also can lead to the under reporting of the real incidence of Lyme disease. The artificially low figures are in turn used by researchers to reinforce their claim that Lyme disease is actually quite rare. Thus, the cycle of denial is complete. The
facts, of course, strongly suggest that Lyme disease is seriously under diagnosed. New testing techniques presented at the international conference [6] indicate that Lyme disease will be found to be significantly more common than previously recognized.

The rejecting of the offending abstracts at the conference had much more to do with their conceptual challenge to current paradigms in Lyme disease research than with their alleged scientific deficiencies. Good science is as much about asking the right questions as it is the sensible pursuit of answers, and many Lyme disease patients do not feel that the mainstream Lyme disease researchers are asking the right questions.

The existing theories need to be reevaluated in light if the emerging evidence on chronic infection in late Lyme disease.

Carl Brenner Lamont-Doherty Geological Observatory of Columbia University Palisades, NY 10964

References: [1] L.H. Sigal, Am. J. Med. 88, 577 (1990) [2] V. Preac-Mursic et al., Infection 17, 355 (1989) [3] K. Liegner, C. Rosenkilde, G Campbell, T. Quan, D. Dennis, "Culture confirmed treatment failure of cefotaxime and minocycline in a case of Lyme meningoencephalomyelitis in the United States" (Abstr. #63, Fifth Int'l Conference on Lyme Borreliosis, Arlington, VA, 1992); E. Masters, P. Lynxwiler, J Rawlings, "Spirochetetemia two weeks post-cessation of six months of continuous p.o. amoxicillin therapy" (Abst. #65 Fifth Int'l Conference on Lyme Borreliosis, Arlington, VA, 1992) [4] Y. Ma, A. Sturrock, J. Weis, Infect. Immun. 59, 671 (1991). [5] Th. Haupl et al., "Persistence of Bb in chronic Lyme disease: altered immune regulation or evasion into immunologically privileges sites?" (Abstr #149, Fifth Int'l Conference of Lyme Borreliosis, Arlington, VA, 1992) [6] K. Liegner, C. Garon, D. Dorward, "Lyme borreliosis studies with the Rocky Mountain Laboratory (RML) antigen capture assay in urine" (Abstr
#104, Fifth Int'l Conference on Lyme Borreliosis, Arlington, VA, 1992)

*****=*****

DATE: January 27, 1993 Note: Thanks to Ralph Yozzo for submitting this item.

CHICAGO (UPI) -- Deer ticks, which transmit Lyme disease, seem to prefer biting people wearing clothes, a Connecticut doctor reported Tuesday. In a letter to the Journal of the American Medical Association, Dr. Henry Feder Jr. of the University of Connecticut Health Center in Farmington, Conn., said he found that among more than 300 people at a nudist camp, the only deer tick bites were reported by persons who were wearing clothes. What was surprising was that deer tick bites were very unusual occurrences at the camp,'' Feder said. `This was not because nudists could not identify deer tick bites, as many of the nudists reported deer tick bites that occurred at their permanent homes.'' Experts generally recommend that people wear long-sleeve shirts and long pants in deer tick areas to deter bites. However, Feder said the deer ticks actually apparently prefer to get underneath clothing, such as under long pants not tucked into socks. Only one case of Lyme disease-associated symptoms had been identified by doctors treating the nudists, Feder said, even though the camp was in
the deer tick's ideal environment. One explanation is that although deer are present, deer ticks are not yet established. A second explanation is that deer ticks do not like nudists, as ticks prefer to do their biting under cover,'' he said. A more formal study was being planned, he said. Lyme disease is a tick-borne illness that initially often causes a rash and flu-like symptoms such as fever, fatigue and aches. These symptoms may be followed weeks or months later by neurologic, heart or joint abnormalities. The disease was first recognized in 1975 in Lyme, Conn., but has been identified in at least 43 states and in other countries.

*****=*****

SOURCE: The Lyme Times (As the article is very long and I can't seem to contact the folks at the LD Times, I will paraphrase)

Family physician Dr. Ed Masters of Cape Girardeau, Missouri and the CDC are locked in a battle over the reporting of LD in that state. Since the CDC has labeled Missouri "non-endemic," they are questioning his diagnoses. The patients, unfortunately, are trapped in the middle.

Dr. Masters sees EM rashes in many of his patients and the biopsies of these lesions from several independent labs confirm the presence of spirochetes. Dr. Masters' patients also have positive ELISA antibody tests and positive PCR tests. Patients develop Herxheimer reactions to antibiotics and show improvement with the therapy. Finally, these patients meet and exceed the CDC's clinical diagnostic criteria for LD.

On top of all this, some Missouri ticks been found to be both stain and PCR positive.

However, the CDC refuses to acknowledge that LD is a problem in Missouri. As their defense, they claim that Dr. Masters has failed to grow and sustain the spirochetes in the BSK-II culture medium. This, apparently, invalidates all other data. The CDC now officially refers to the Missouri cases as "Lyme-like." The first four cases of LD Dr. Masters reported to the Missouri Department of Health were ordered removed from the computer files.

Dr. Masters claims that the culture problems are attributable to technical problems. He charges that the CDC is arbitrarily changing the rules of the game when it sees fit. The CDC cites unpublished reports that show no evidence of LD infection in local ticks.

Now, Dr. Masters and Dr. David Dennis, coordinator of the CDC's LD program, have locked horns over this issue. Dr. Dennis insists that sustainable cultures are required to prove the existence of Bb. Dr. Masters points out that easy culturability is not required of many other bacteria, viruses, syndromes, MS, rheumatoid arthritis, etc.

Dr Masters concludes that his "...experience with the CDC over the past few years leaves [him] with the personal opinion that the CDC embraces "the possibility that Lyme disease... occurs in Missouri" with the same enthusiasm and objectivity that Karl Marx would in evaluating the possibilities that capitalism and free markets are good ideas."

More to come as this drama unfolds...

III. ***** QUESTIONS 'N' ANSWERS *****

Here are the first four questions submitted to the LymeNet. Additional responses are still welcome.

*****=*****

Sender: [email protected] (Joe Wells) Subject: How accurate are Lyme disease tests?

How accurate are the various tests for Lyme disease? For each test, what is the proportion of negatives that are false and what is the proportion of positives that are false?

RESPONSE: Ed- A study published in the Archives of Internal Medicine [vol 151, September 1991, pgs 1837-40] concludes that the sensitivity of LD antibody tests ranges from 13% to 73%, depending on the lab being used. False positives were noted in 0% to 27% of patients. The test with the best sensitivity was from Hillcrest Biologicals (Cypress, CA). Their false positive rate was also within reason. You might wish to investigate testing at this site. The problem of lack of test standardization has been raised dozens of times by researchers, clinicians and LD advocates. The CDC is said to be working on it. Dr. David Dorward of the NIH's Rocky Mountain Labs will be sharing his thoughts on testing in a future issue.

*****=*****

Sender: [email protected] (Patricia Emily) Subject:

Does anyone have good information on tick borne diseases? My sister has suffered several tick and flea bites last summer. She has not felt well for the last several months. She has flu-like symptoms; generally not feeling well. She has some minor joint inflammation in her right hand and toes. She says sometimes her finger tips and toes feel inflamed. Lately, she has woken up in the morning with her right hand closed and stiff. She says it takes about 30 seconds to work it open.

She has been to numerous doctors hoping for a diagnosis and relief from the symptoms. She has been diagnosed with things like rheumatoid arthritis, lupus, lyme disease (the tick connection). She has had the test for lyme disease and the results came back "equivocal" meaning not positive or negative. The doctor how is treating her for lyme disease since they will treat if it is suspected.

The antibiotic treatment for lyme disease is Suprax 400 mg, BID for 30 days. She said that she feels better after only a couple of days of antibiotics.

Does anyone have a clue what is going on here, or have similar experiences?? She has had a hard time finding knowledgeable doctors, and still does not have a definite diagnosis. I would be interested in hearing from people who have seen similar cases and can perhaps give some insight.

What is the prognosis for someone with this type of disease?

RESPONSE: Ed- Although net-diagnoses are not advised, your sister does exhibit many LD symptoms. If she is comfortable with her current doctor, she should continue her prescribed treatment and see what happens. If not, she should seek out an LD knowledgeable physician in the area (while continuing the treatment). The LD Foundation operates a physician referral service. You can contact them at 800-886-LYME. The prognosis? It's very difficult to say. I would invite additional reader response to this question.

*****=*****

Sender: "Ralph E. Yozzo" <[email protected]> Subject: Newsletter comments and questions

Thank you very much for this newsletter. It makes one feel that there are concerned people out there with similar problems.

Comment: In the 10/6/1992 Poughkeepsie Journal (Upstate NY), there was an article saying that a record of 144 case of Lyme disease (LD) was logged in August, 1992. (This problem is more widespread than some people think!)

Question: Have studies been done to see what groups are more susceptible to chronic Lyme disease problems (e.g., chronic arthritis)? For instance, do the elderly or out-of-shape people have a better chance of having long term LD problems?

What is the optimal drug, dosage, and duration to treat LD?

RESPONSE: Ed- A study By Dr. Allen Steere et al in the New England Journal [vol 323 number 4, July 26, 1990, pgs 219-223] suggests that genetics play a role in determining chronicity. The study concludes that particular "Class II major histcompatibility genes determine a host immune response to Bb that results in chronic arthritis and a lack of response to antibiotic therapy." The HLA-DR4 and HLA-DR2 "markers" were found in a large percentage of chronic LD arthritis patients. You can get tested for these genetic markers. You may wish to discuss this option with your doctor. As for the "optimal" treatment... It does not exist. Each set of symptoms has a "recommended" treatment. In the next issue, I will publish some guidelines set forth by Dr. Philip Paparone, director of infectious disease at the Atlantic City Medical Center, NJ.

*****=*****

From: Preventive Medicine <[email protected]> Subject: Re: [mcg2: LymeNet Newsletter vol#1 #01]

WOW! Thanks, this is most helpful. Previously, Sandra Evans had sent me a copy of: M. Cinco, et. al. 1989. Characterization of the first tick isolate of BB from Italy. APMIS 97:381-382. The article lists the area of Liguria (near here) as endemic for Lyme borreliosis. This is also the area where 7000+ CONUS based troops will be training during part of REFORGER 93. I will be working to obtain additional infor from host nation sources. However, my access to current scientific literature base in CONUS is very limited. If anyone on the Lyme net has info, articles, training materials etc. etc. related to Lyme especially in Med/Africa, especially among deploying US Forces I would greatly appreciate it if they would pass along to me. In addition to this field ento/PM issue I also plan a mini-review for health care providers, e.g. we have had at least one case (stage 4?) of a spouse of a retired SFC who was bitten right here in Vicenza. Anyway, good work and I'd like to be involved in the info exchange on Lyme Ciao,
LTC Jeff Drifmeyer, Chief, Preventive Medicine Service, USAMEDDAC-Vicenza, ITALY.

RESPONSE: Ed- Hummm... tough one. The best I can do is refer you to the Italian researchers who attended the V Int'l Conference on LD last May. They are doing work on the clinical manifestations of LD in that country. They are Patrizia Monteforte, Guido Rovetta, Laura Buffrini, Vincenzo Garzia, Aurora Parodi, G. Luigi Mancardi, Franco Crovato and Gerolamo Bianchi, University of Genova, Genova and U.S.L. XVIII, Chiavari, Italy. Good luck... Let us know what you learn.

IV. ***** OP-ED SECTION *****

This section is open to all subscribers who would like to express an opinion. By: John Setel O'Donnell

[An issue last December of the] New York Times carried a report of an article published in [the] New England Journal of Medicine by a group led by Eugene Shapiro of Yale. The article headline is "Study of Lyme Disease Sees Low Risk in Ticks". The reported conclusion of the paper is that prophylactic treatment with antibiotics upon a deer tick bite is not warranted.

This result conflicts with a paper published in NEJM this past summer by Magid et al. which comes to the opposite conclusion.

Other research results have established the fact that: - Test technology is extremely poor (CDC, First National Conference on Lyme Disease Testing, 11/90) - The Lyme spirochete disseminates very early in the course of infection into the CNS (Luft, Steinman, et. al JAMA 267, 10), where it is resistant to treatment; - The spirochete invades human endothelial cells (Ma, Sturrock, Weiss, Infec Immun 59) and fibroblasts (Georgilis et al., Fifth Int'l Conference on Lyme Borreliosis, abst. 165), which protect it from antibiotics including ceftriaxone. - Patients see an average of three doctors before they are accurately diagnosed with Lyme. Many are told they have lupus, multiple sclerosis, scleroderma, and/or psychiatric disorders (Fallon, Neilds, Fifth Int'l Conf LB, abst. 143). 40% are referred to psychiatrists, about a third are put on psychoactive drugs. - Letting Lyme go untreated for more than a few weeks makes it very difficult and extremely expensive to eradicate. The CDC's New Jersey
study of children with Lyme found that direct medical costs averaged $96,000 per child. Children lost at least half of a school year.

Yale's publication of yet another flawed, nearly corrupt paper, aided by their press flacks who got the Times to lead with "...Low Risk", is a detriment to public health, fueled by their irrational obsession with insisting that Lyme is relatively harmless and easily cured, despite the now voluminous evidence to the contrary.

The facts are in, and the Yalies are lying. Thousands more will suffer because of their lies.

Lyme is a devastating, incurable disease in its later stages. It is very difficult to unequivocally detect in its early stages. Despite at least tens of thousands of new cases annually (CDC, David Dennis) the 1991 Federal research budget toward a cure was less than $200,000. The distortions and emotionally rather than factually based positions that researchers at Yale and elsewhere have put forth are largely responsible for this national scandal.

I urge you to write to NIH and NEJM about this issue. Ignoring the disease, its consequences, and its persistence will not make it go away. Only better research will. We desperately need public awareness and public monies to bring this about.

John Setel O'Donnell [email protected] Equator Technologies, Inc. 206-328-6544 voice/fax Seattle, WA Read everything by Alice Miller.

V. ***** PARTIAL BIBLIOGRAPHY FOR FURTHER READING *****

The following list of references was complied by Carl Brenner and John O'Donnell. We will present a few every week for the next few issues of the LymeNet newsletter.

On mechanism of persistence (e.g., intracellularity):

Ma Y, Sturrock A, Weis J. Intracellular localization of Bb within human endothelial cells. Infect and Immun 1991;59(2):671-678

Haupl T, et.al. Persistence of Bb in chronic Lyme disease: altered immune regulation or evasion into immunologically privileged sites? Abstr. #149, Fifth Int'l Conf on Lyme Borreliosis, Arlington VA 1992.

Montgomery RR, et. al. The fate of Bb in mouse macrophages: destruction, survival, recovery. Abstr. #143, same conference. (Persistence of Bb in mouse macrophages.)

On other explanations (e.g., auto immunity) for persistence of symptoms after treatment:

Sigal LH, Tatum AH. Lyme disease patients' serum contains IgM antibodies to Bb that cross-reacts with neuronal antigens. Neurology 1988; 38:1439-1442.

Steere AC, Dwyer E, Winchester R. Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles. N Eng J Med 1990;323:219-223

On cognitive/psychological symptoms:

Krupp LB, et. al. Cognitive functioning in late Lyme borreliosis. Arch Neurol 1991:48:1125-1129 (Majority of patients studied had measurable neuropsych deficits after treatment; not clear if this is due to persistent infection or toxic fallout from systemic post-infectious syndrome. *Highly recommended*.)

Fallon BA and Nields JA. Psychiatric manifestations of Lyme borreliosis: a controlled study of major depression. Abstr #47, Fifth Int'l Conf on Lyme Borreliosis, Arlington, VA 1992 (Major depression three times more common among patients with Lyme than among patients with non-Lyme arthridities) [Lyme has also been shown to cause psychosis, much like syphilis]

VI. ***** JARGON INDEX *****

Bb - Borrelia burgdorferi - The scientific name for the LD bacterium. CDC - Centers for Disease Control - Federal agency in charge of tracking diseases and programs to prevent them. CNS - Central Nervous System. ELISA - Enzyme-linked Immunosorbent Assays - Common blood antibody test EM - Erythema Migrans - The name of the "bull's eye" rash that appears in ~60% of the patients early in the infection. IFA - Indirect Fluorescent Antibody - Common blood antibody test. LD - Common abbreviation for Lyme Disease. NIH - National Institutes of Health - Federal agency that conducts medical research and issues grants to research interests. PCR - Polymerase Chain Reaction - A new test that detects the DNA sequence of the microbe in question. Currently being tested for use in detecting LD, TB, and AIDS. Spirochete - The LD bacterium. It's given this name due to it's spiral shape. Western Blot - A more precise antibody test.

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