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Volume: 3
Issue: 08
Date: 30-May-95


Table of Contents:

I.    NIAID: Lyme Disease Agent Changes Its Surface Before
      Infecting People
II.   Q&A: Experience with timentin or cefpodoxime in LD? (A)
III.  JAOA: Lyme Disease With Concurrent Ehrlichiosis  
IV.   LYMENET: National LymeNet Suffers Hardware Failure
V.    About The LymeNet Newsletter


Newsletter:

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*                  The National Lyme Disease Network                  *
*                         LymeNet Newsletter                          *
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IDX#                Volume 3 - Number 08 - 5/30/95
IDX#                            INDEX
IDX#
IDX#  I.    NIAID: Lyme Disease Agent Changes Its Surface Before
IDX#        Infecting People
IDX#  II.   Q&A: Experience with timentin or cefpodoxime in LD? (A)
IDX#  III.  JAOA: Lyme Disease With Concurrent Ehrlichiosis  
IDX#  IV.   LYMENET: National LymeNet Suffers Hardware Failure
IDX#  V.    About The LymeNet Newsletter
IDX#


QUOTE OF THE WEEK:

     "The lack of OspA and the possible shutdown of OspC by
     spirochetes after they enter into humans may play a role
     in persistent infection and the spirochetes' evasion of
     the immune response"


     -- Tom Schwan (See Section I)


I.    NIAID: Lyme Disease Agent Changes Its Surface Before
     Infecting People
----------------------------------------------------------
For Immediate Release
DATE: April 5, 1995


BETHESDA, MD -- The Lyme disease bacterium changes its coat prior
to being transmitted from ticks to humans and other mammals,
scientists from the National Institutes of Allergy and Infectious
Diseases (NIAID) and their colleagues have discovered, a finding
that has important implications for designing diagnostic tests and
vaccines to control he disease.


As noted in their April 1, 1995 Proceedings of the National Academy
of Sciences, this adaptation likely evolved to ensure that the
bacteria can be transmitted to and thrive in two very different hosts,
ticks and mammals.  In the United States, the spiral-shaped bacteria
are passed on to people through the bites of infected back-legged
ticks.


According to NIAID Director Anthony S. Fauci, M.D., "This new finding
underscores why investment in basic research is so important.  The
specific adaptation of the Lyme disease spirochete that has now been
identified will assist efforts to improve the diagnosis and prevention
of this illness."


The investigators knew from previous studies that when a tick first
becomes infected, the Lyme spirochetes settle in its midgut and make
OspA surface protein.  But as the new laboratory experiments reveal,
when an infected tick subsequently attaches to a warm-blooded
mammal and begins feasting on blood, two environmental cues --
something in the blood itself and an increase in temperature -- signal
the spirochete to stop producing OspA and make OspC surface protein
instead.


"We believe that OspC is critical for the dissemination and
transmission of Lyme spirochetes during the tick feeding," comments
lead author Tom G. Schwan, Ph.D., a microbiologist with NIAID's
Rocky Mountain Labs (RML) in Hamilton, Mont.


Describing the relevance of their observations to diagnosis, Dr.
Schwan says their research suggests that OspC is the first abundant
surface protein the immune system encounters when spirochetes
enter the body, which explains why people rarely make an antibody
response to OspA and why they develop antibodies to OspC early on.
"The lack of OspA and the possible shutdown of OspC by spirochetes
after they enter into humans may play a role in persistent infection
and the spirochetes' evasion of the immune response," adds Dr.
Schwan.  When U.S. Lyme experts recently drafted standards for the
Western blot -- a confirmatory diagnostic test that detects antibodies
to specific proteins -- they agreed that OspC should be one of the
required proteins to look for in the patient's sera.


Their findings also bear on vaccine development.  Currently, two
companies have OspA-based Lyme vaccines in human trials.  In
experiments with mice, other researchers have shown that these
vaccines work in a non-traditional way.  When the tick feeds in a
vaccinated mouse, the tick ingests anti-OspA antibodies.  These
antibodies kill the spirochetes inside the tick, preventing migration
of the spirochetes from the tick to the host animal rather than
preventing infection or disease inside the host.  According to
Edward McSweegan, Ph.D., Lyme disease program officer for NIAID,
"This new report suggests that like OspA vaccines, an OspC vaccine
would also be an anti-transmission vaccine.  In this light, it would
be worth considering combining both proteins into one vaccine."


Nymphal ticks -- the immature, freckle-sized form that most often
transmits Lyme disease -- usually complete feeding within three to
six days.  In their report, the scientists write that the spirochete
"is rarely if ever transmitted by ticks to mammals during the first
two days of attachment and feeding.  From two days onwards, however,
the frequency of transmission of spirochetes by ticks increases
dramatically."  In their experiments, they successfully infected mice
by inoculating them with infected midguts from ticks that had fed
for three or more days and therefore had begun producing OspC.


This lag time in transmission during early tick feeding had been
attributed solely to the spirochete's location in the midgut.
But the new research suggest that the change to OspC begins while
the spirochete is still in the midgut and may be required for the
spirochete to migrate out of that location.


As a tick feeds, the spirochetes multiply, pass through the midgut
wall to the tick's bloodlike fluid, invade the salivary glands, and
are transmitted to the animal or human host in tick saliva.  "This
entire phenomenon takes time, during which both ticks and spirochetes
first warm to approximately 37 degrees C, when ticks attach to the
host's skin [TGS, unpublished data]," write the scientists.


Dr. Schwan's team found that spirochetes produce OspC at 32 degrees
C to 37 degrees C, but not at 24 degrees C.  Merely raising the
temperature, however, does not cause the switch.  This change also
required some as yet unidentified signal or nutrient in blood.


Lyme disease mainly affects people living in the northeastern and
upper north-central United States, and along the northern Pacific
Coast.  The Centers for Disease Control and Prevention (CDC) will
hot have the final tally of the 1994 Lyme disease cases until all
states submit their reports, but the provisional total is 12,973
based on the 41 states that have reported to date.


It treated promptly with antibiotics, Lyme disease symptoms usually
resolve.  People who do not receive prompt treatment can develop
chronic arthritis and neurological symptoms.


Borrelia burgdorferi, the Lyme spirochete, was isolated and identified
in 1981 by NIAID RML researchers Willy Burgdorfer, Ph.D., hon. M.D.,
and Alan Barbour, M.D.  Since then the Institute has maintained a
productive intramural Lyme disease research effort at RML.


Dr. Schwan's collaborators on the paper include Patricia A. Rosa,
Ph.D., of RML; and Joseph Piesman, Ph.D., William T. Golde, Ph.D.,
and Marc C. Dolan of the CDC in Fort Collins, Colo.


NIAID, a component of the National Institutes of Health (NIH),
supports biomedical research to prevent, diagnose and treat illnesses
such as AIDS, tuberculosis, asthma and allergies.  NIH and CDC are
agencies of the U.S. Public Heath Service, part of the U.S.
Department of Health and Human Services.



=====*=====


II.   Q&A: Experience with timentin or cefpodoxime in LD? (A)
-------------------------------------------------------------
Sender: Philip W. Paparone, D.O., Lyme Disease Center for South
       Jersey


We have attempted to procure information concerning Cefpodoxime
and invitro sensitivity of the Borrelia burgdorferi, and the
manufacturer of Cefpodoxime-Vantin does not have data to support
further investigation of the drug clinically since it appear not
to have any activity against the Borrelia invitro.


However, with Timentin it is know that Pipricillin is the same
class as Ticarcillin, which is contained within Timentin, does
have activity against Borrelia burgdorferi, and also that
Clavulinic acid is active against the Borrelia burgdorferi in the
test tube.  There would possibly be synergy; however, this combination
has not been tested.  An attempt at testing Augmentin, to see if
there was any synergistic effect was initiated by ourselves at
the Lyme Disease Center of South Jersey, but then the FDA
discontinued it stating that Amoxicillin was already known to be
effective.  They did not want to consider the possibility of synergy.


As far as antibiotics for Thromocytopenia patients please note the
article about ehrlichiosis [abstract in section III] which can
demonstrate significant Thrombocytopenia as a clue to the possibility
of ehrlichiosis.



=====*=====


III.  JAOA: Lyme Disease With Concurrent Ehrlichiosis
-----------------------------------------------------
AUTHORS: Paparone PW, Glenn, WB
ORGANIZATION: Lyme Disease Center for South Jersey
REFERENCE: JAOA 1994 July;97(7): 568-77
ABSTRACT:


Lyme disease constitutes a major health hazard with an increased
incidence throughout the United States, in particular the eastern
states.  Human ehrlichiosis, also a tick borne illness, has recently
been identified.  It is characterized by fever, headache, malaise,
leukopenia, thrombocytopenia, and elevated liver enzyme titers, and
has been reported to occur mainly in the South Central and South
Atlantic states.  As with Lyme disease, most patients have a history
of tick exposure.  These two diseases may be difficult to
differentiate clinically.  Physicians must consider the possibility
of both infections when patients become ill with a systemic illness
after tick exposure.  Although certain demographic and clinical
features are characteristic of these diseases, they can be misleading.
Only serological evidence can confirm the diagnosis.  Two cases of
concurrent Borrelia and Ehrlichia infections have been previously
reported.  The authors herein describe a third case that further
illustrates the potential diagnostic dilemma posed by the concurrence

of these two entities.


=====*=====


IV.   LYMENET: National LymeNet Suffers Hardware Failure
--------------------------------------------------------
DATE: May 26, 1995
BYLINE: By Marc Gabriel


The National LymeNet service suffered a major hardware failure on
May 23.  The system is not currently online due to this failure.
The Lyme Disease Network of NJ is currently reviewing the situation
and will keep readers of the Newsletter updated on the latest
developments.



=====*=====


V.    ABOUT THE LYMENET NEWSLETTER
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