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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


*                  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.


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

DATE: November 5, 1993, Friday
SECTION: Section S; Page 2, Column 1

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.


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.


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

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


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

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
Western Blot - A more precise antibody test.


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