LymeNet Newsletter Volume 1 Issue 26

Volume: 1
Issue: 26
Date: 24-Nov-93

Table of Contents:

PHILADELPHIA INQUIRER: Lyme Surge Has County Officials Scratching Heads LITERATURE REVIEW: 1. Lyme Disease: The Sensible Pursuit of Answers 2. Long Term Treatment of Chronic Lyme Arthritis with Benzathine Penicillin 3. Psychiatric Manifestations of Lyme Borreliosis 4. Neuroendocrine-immune Interactions ABSTRACT: (J Infect Dis) Topical Prophylaxis for Lyme Disease After Tick Bite in a Rodent Model ABSTRACT: (Infect Immun) OspB Mutant of Borrelia Burgdorferi Has Reduced Invasiveness in Vitro and Reduced Infectivity in Vivo

Newsletter:

***************************************************************************** * Lyme Disease Electronic Mail Network * * LymeNet Newsletter * ***************************************************************************** Volume 1 - Number 26 - 11/24/93

I. Introduction II. News from the Wires III. Jargon Index IV. How to Subscribe, Contribute and Get Back Issues

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

This issue of the Newsletter features:

* News about a "surge" in LD cases in one New Jersey county * A literature review by Dr. Lloyd Miller * Two medical abstracts: - Topical prophylaxis for Lyme disease after tick bite in a rodent model - An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo.

-Marc.

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

Source: PHILADELPHIA INQUIRER Abstracts DATE: November 5, 1993, Friday SECTION: Section S; Page 2, Column 1 HEADLINE: LYME SURGE HAS COUNTY OFFICIALS SCRATCHING HEADS BYLINE: BY JEFFREY BRODEUR

Hunterdon County [NJ] health officials, searching urgently for link behind 322 percent increase in Lyme disease cases there, have solicited help from Federal Centers for Disease Control and Prevention; Health Dept Dir John Beckley says CDC investigators will coordinate data from some of 227 Hunterdon patients who contracted disease in first nine months of 1993; county reported 87 cases of Lyme disease in 1992, and health officials are at loss to explain jump.

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Sender: "Lloyd E. Miller,DVM" <[email protected]> Subject: Interesting articles

Four articles of interest have recently crossed my desk.

1. Liegner LB: Lyme Disease: the Sensible Pursuit of Answers. Journal of Clinical Microbiology 1993;31(8):1961-63.

Excellent commentary addressing chronic persistent infection, prolonged antibiotic treatment of chronic persistent Lyme disease, seronegativity and the exclusion of seronegative Lyme patients from research models, treatment on tick bite to prevent disease, "pulse" antibiotic therapy for chronic disease (4 grams of cefotaximine every 8 hours for 24 hours one day per week). This is a reasonable non-sensational discussion of the current evidence relating to these topics. I recommend that everyone read this article. Author's address: 8 Barnard Road, Armonk, New York 10504.

2. Cimmino MA,Silvano A: Long term treatment of chronic Lyme arthritis with benzathine penicillin. Annals of the Rheumatic diseases 1992;51:1007-08.

The article describes the long term treatment of two patients with chronic Lyme arthritis with intramuscular benzathine penicillin (1.2 *10(6)U/week). The authors feel they have cured their patients. The patients had been previously treated with ceftriaxone, tetracycline, minocycline and shorter courses of penicillin without cure. This is a European article and penicillin has been reported to be more effective in Europe than in the USA but I am unaware of any real clinical trials to document this. There is a need to study the possible effectiveness of this protocol. It would be much easier and much less expensive than many of the currently used parentral treatment regimes.

3. Fallon B,Nields J et al: Psychiatric Manifestations of Lyme Borreliosis. J Clin Psychiatry 1993;54(7):263-68.

Another very important article by these authors concerning the psychiatric manifestations of LD. Using a structured interview (SCID) three patients who had developed a psychiatric disorder for the first time after infection with Bb were studied. During LD one patient had major depression and panic disorder, one patient had an organic mood syndrome with both depression and mania, and the third patient had panic disorder. The disorders remitted after adequate antibiotic treatment. The authors point out the need for mental health professionals to be aware of the psychiatric manifestations of LD.

By the same authors: 1. Fallon BA,Nields JA et al: The neuropsychiatric manifestations of Lyme borreliosis. Psychiatric Quarterly 1992;63(1):95-117.

Both of these articles should be read by every Lyme patient and medical professional. There is a need for these articles to be republished in a more widely read media than just the psychiatric journals. Authors address for reprints: Brian A. Fallon, M.D., Ph.D. New York State Psychiatric Institute 722 west 168th Street, Box 13 New York, New York 10032

A variation on "pulse" therapy was presented at the V International Conference on Lyme Borreliosis held in Arlington, Virginia in May of 1992.

"The use of programmed intermittent antibiotic treatment to prevent recurrence of Lyme Borreliosis" presented as a poster by Edmondo R. Mandac, East Ohio regional Hospital, Martins Ferry, Ohio.

From the abstract: The subject in this case, a 15 year old patient with advanced Lyme Borreliosis, received a course of both intravenous (4 weeks cefotaxime and 4 weeks ceftriaxone) and oral (cefixime for 10 months) antibiotics. The cefixime was discontinued for one month. Symptoms persisted and worsened. The patient was treated with a 4 week course of intravenous cefotaxime wherein symptoms abated. Subsequent to this 4 week course, the patient received daily doses of intravenous cefotaxime for one week out of a month and exhibited a Jarish-Herxheimer reaction with this treatment. The one week per month regimen of intravenous cefotaxime was continued until the Jarish-Herxheimer reactions no longer occurred. In an effort to avoid relapse of symptoms and the necessity of repeating a full course of treatment, the use of programmed intermittent antibiotics may help to insure the latent Borrelia are eradicated. Moreover, due to the lack of reliable teat for determining the eradication of the spirochete, the
observation of a Jarish-Herxheimer reaction suggests the latent presence of the Spirochete and the continued intermittent dosing necessary.

Needless to say this idea was received with criticism from certain quarters of the Lyme research community present. Given the nature of Bb intermittent ("pulse") treatment may actually be an appropriate treatment strategy.

4. Seymour R: Neuroendocrine-immune interactions. The New England Journal of Medicine 1993;329(17):1246-1253.

This is a review article in the NEJM's Mechanisms of Disease series. The interaction of the neural, endocrine and immune systems are demonstrated. It mentions that the neuropathologic effects of Bb may be mediated by cytokines produced by activated glia and immune cells that enter into the brain from the circulation.

It discusses the pituitary-adrenal response to disease mentioning that reduced pituitary and adrenal responses to corticotropin-releasing hormone and slightly reduced plasma cortisol concentrations have been reported in patients with chronic fatigue syndrome(CFS). Has anyone studied this in Lyme disease? Whether the response precedes the disease or is a consequence of the disease is not worked out. It is further stated that patients with CFS were depressed and that patients with depression have reduced pituitary and adrenal responses to corticotropin-releasing hormone, although their plasma cortisol concentrations are characteristically slightly elevated.

There is considerable food for thought in this article for all of us interested in the pathogenesis of LD -- indeed in the pathogenesis of disease. Effective treatment for LD, especially the chronic persistent disease, is dependent on discovering the mechanisms by which Bb produces its effects on the body and its systems. It is also obvious from this article that very little is known about how these systems actually respond to or influence disease expression. Chronic persistent disease is described more commonly in females. Symptoms in females often vary according to the menstrual cycle. This must be neuro-endocrine-immune related but how? The psychiatric manifestations described by Dr. Fallon must certainly be influenced (caused?) by the effects of the interactions of these systems. Is it possible that a number of psychiatric diseases are actually responses to antigens or infectious agents not yet identified causing perturberences in the neuro-endocrine-immune systems?

It seems to me that identified pathogenic mechanisms of Lyme disease might be of great importance as a model for other diseases. The similarities to so many other diseases may not be totally by coincidence. In particular the diseases of Chronic Fatigue Syndrome (CFS), Fibromyalgia (FM), and Multiple Sclerosis (MS) have very similar disease manifestations. Since the cause of Lyme disease is known, and if disease mechanisms can be elucidated, then this information might be of great value in working out the mysteries of these other diseases. The reverse is also true, that elucidated pathogenic mechanisms of these other diseases might be used as clues to figuring out the effects Bb has on the body.

I have a hard time believing that so may people affected by the chronic manifestations of LD, CFS, FM and MS have systems running out of control without some kind of underlying stimulus. In the case of LD this would appear to be chronic persistent infection. The underlying stimulus for the other three have not yet been found.

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TITLE: Topical prophylaxis for Lyme disease after tick bite in a rodent model AUTHORS: Shih CM; Spielman A ORGANIZATION: Dept. of Tropical Public Health, Harvard School of Public Health REFERENCE: J Infect Dis 1993 Oct; 168 (4): 1042-5

ABSTRACT: To determine whether infection with the Lyme disease spirochete (Borrelia burgdorferi) can be aborted by topical application of antibiotic to the site of tick attachment, individual infected nymphal deer ticks (Ixodes dammini) were permitted to feed on the ears of mice, and various antibiotics were applied to the feeding site at intervals after the replete infecting tick had detached. Infection in each mouse was determined by serology and by xenodiagnosis at 4 weeks after the bite of the infected tick. None of these mice became infected when antibiotic was topically applied to the site of tick attachment within 2 days after the spirochete-infected ticks had detached. In contrast, all nontreated and virtually all solvent-treated mice became persistently infected. Thus, persistent infection by the agent of Lyme disease can be aborted by appropriate topical application of antibiotic.

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TITLE: An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo. AUTHORS: Sadziene A; Barbour AG; Rosa PA; Thomas DD ORGANIZATION: Department of Microbiology, University of Texas Health Science Center REFERENCE: Infect Immun 1993 Sep; 61 (9): 3590-6

ABSTRACT: Most Borrelia burgdorferi strains have two major surface proteins, OspA and OspB. In the present study, we selected from a clonal population of infectious B. burgdorferi an OspB escape mutant, identified the genetic basis for this phenotype, and evaluated its functional activities. Selection with the anti-OspB antibody H614 was performed in vitro in medium and extended in vivo in scid mice. Mutants with a truncated OspB protein were selected at a frequency of 1 x 10(-5) to 3 x 10(-5). After no major rearrangements in DNA were detected, sequence analysis of the mutant's ospAB locus revealed a single base change in the consensus ribosomal binding sequence for ospB and a single nucleotide deletion in the ospB gene itself. The effect of these mutations was reduced expression of a truncated OspB protein. When functional abilities of the wild type and mutant were compared, the mutant had a threefold-lower capacity to penetrate a human endothelium umbilical vein cell monolayer. Infectivity of wild-type and mutant cells for scid
mice was evaluated by culturing different organs, and the median infectious dose was calculated. The inoculum of mutant cells for infecting the mice was 30- to 300-fold higher than that of wild-type cells. This study shows that reduced size and expression of OspB are associated with lowered virulence of B. burgdorferi. Selection of mutants that to some degree remain infectious is one approach to defining the role of different surface proteins in the pathogenesis of Lyme disease.

III. ***** 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 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 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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