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Volume: 6
Issue: 08
Date: 21-Aug-98


Table of Contents:

I.    LYME TIMES: Antibodies may be Hidden in Immune Complexes
II.   EPIDEMIOL INFECT:  Transmission risk of Borrelia burgdorferi
      sensu lato from Ixodes ricinus ticks to humans in southwest
      Germany
III.  J NEUROL NEUROSURG PSYCHIATRY: Differential diagnosis of multiple
      sclerosis: contribution of magnetic resonance techniques.
IV.   N ENG J MED: Persistent parasitemia after acute babesiosis.
V.    EPIDEMIOL MIKROBIOL IMUNOL: Educational status of the Czech
      population about Lyme borreliosis and experience with tick bites
IV.   ABOUT THE LYMENET NEWSLETTER


Newsletter:

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                   Volume 6 / Number 08 / 21-AUG-98
                                INDEX


I.    LYME TIMES: Antibodies may be Hidden in Immune Complexes
II.   EPIDEMIOL INFECT:  Transmission risk of Borrelia burgdorferi
     sensu lato from Ixodes ricinus ticks to humans in southwest
     Germany
III.  J NEUROL NEUROSURG PSYCHIATRY: Differential diagnosis of multiple
     sclerosis: contribution of magnetic resonance techniques.
IV.   N ENG J MED: Persistent parasitemia after acute babesiosis.
V.    EPIDEMIOL MIKROBIOL IMUNOL: Educational status of the Czech
     population about Lyme borreliosis and experience with tick bites
IV.   ABOUT THE LYMENET NEWSLETTER



=====*=====


I.    LYME TIMES: Antibodies may be Hidden in Immune Complexes
--------------------------------------------------------------
Source: the Lyme Times, April-June, 1998, p28
By: Jean Hubbard


Editor's Note: This report was written based on a presentation at the
1998 Lyme Disease Foundation Scientific Conference.  The remainder of
this presentation describes studies using immune complex assays
developed by Dr. Steve Shutzer and his colleagues.  Full appreciation
of those data require graphs and slides which the LymeNet Newsletter
is unable to duplicate.


-----

Classic serologies can be falsely negative -- or remain positive after
infections have cleared -- due to the nature of the "immune complexes"
that are formed when antibodies bind with antigen from the infecting
agent.  Steve Shutzer, MD, of the University of Medicine and Dentistry
of New Jersey, described how these immune complexes develop and the
"powerful effects" they have on what one can find when sampling sera
for antibodies.


Immediately after an infection begins, the infecting organism "begins
proliferating and shedding antigen," a process which takes some time.  
For a while there is a growing load of antigen compared to the
antibody response to it.  Typically, it takes lymphocytes responding
to an antigen four days to differentiate into plasma cells and produce
antibodies directed to the stimulating antigen.  The antibodies
migrate to the antigen and lock onto it, typically making it
vulnerable to destruction by the immune system.  It then takes "a lot
longer," Dr. Schutzer explained, until all available antigen is
complexed and the surplus "free" antibodies are of sufficient number
to be detectable by an antibody test, "whether the best test or the
worst test."


The same process occurs in all infections, including viruses and other
bacteria.  In Lyme disease, most studies indicate it takes from four
to six weeks for the free antibodies to become detectable.  Before this
point the patient is in an apparent seronegative state.  The only way
to find antibodies during the preceding time would be by using
techniques to capture the immune complexes, pull them apart and
analyze the components.


Because the ongoing interaction between an infectious antigen and the
host's immune response involves several factors, it can result in a
number of different outcomes: Conceivably a person could build up a
lot of antibody and clear the infection, with the antibody response
persisting for months to years; a positive serology in this situation
would be a "false positive."  The antibodies also could decrease and
establish a level, or plateau, that still remains detectable.  Or they
might decrease even further, to a plateau below the threshold of
antibody detection, and the patient would then be antibody negative
on testing whether the infection had cleared or not.


Therefore, according to Dr. Schutzer, once it had been established that
a patient has Lyme disease, diagnostically it no longer matters what
the antibody level is.  Tests for antigen, he believes, are more
likely to be of actual diagnostic significance because if antigen is
found, either it is not being cleared or something is continuing to
produce it.  Antigen detection also allows for earlier diagnosis,
during the period when antigen proliferation exceeds antibody
production.


Dr. Shutzer believes that a more promising strategy than counting
antibodies via serology is to capture the immune complexes and
analyze them for both antibodies and antigen.  In every single
infectious disease that's ever been studied, he claimed, when immune
complexes can no longer be found, that seems to correlate with
elimination of infection.


When evaluating new tests, he cautioned, it is imperative to use the
noncontroversial cases; therefore, in evaluating tests for Lyme
disease, one starts off with people with erythema migrans or
microbiological confirmation of infection in some tissue by PCR or
culture.


Like the other presenters who talked about classic Lyme serologies, Dr.
Shutzer believes that better serologic analyses would look at proteins
unique to B. burgdorferi, including OspA, OspB, and the newly
described p37 and p35, rather than the cross-reacting proteins such
as 41kDa which are tested by classic serologies.  The current
serologies, he said, encourage people to "count the number of bands
and vote on it."


"If you find antibody reactive to p37 and p35, particularly in a
complex where there are also antigens," he observed, "then you're
likely to have active early infection with Lyme disease."


He predicts that more new unique bands will be discovered, enabling
research to "clear up a lot of the current misunderstanding in defining
who had early Lyme disease and who has chronic Lyme disease."



=====*=====


II.   EPIDEMIOL INFECT:  Transmission risk of Borrelia burgdorferi
     sensu lato from Ixodes ricinus ticks to humans in southwest
     Germany
------------------------------------------------------------------
AUTHORS: Maiwald M, Oehme R, March O, Petney TN, Kimmig P, Naser K,
        Zappe HA, Hassler D, von Knebel Doeberitz M
ORGANIZATION: Department of Microbiology and Immunology, Stanford
             University School of Medicine, Palo Alto, CA  94304, USA
REFERENCE: Epidemiology and Infection, in press


The risk of Borrelia burgdorferi infection and the value of antibiotic
prophylaxis after tick bite are controversial. In this study, performed
in two areas of southwestern Germany, ticks were collected from 730
patients and examined by the polymerase chain reaction (PCR) for B.
burgdorferi. To assess whether transmission of B. burgdorferi occurred,
the patients were clinically and serologically examined after tick
removal and during follow-up examinations. Data from all tick bites
gave a total transmission rate of 2.6% (19 patients). Eighty-four
ticks (11.3%) were PCR positive. Transmission occurred to 16 (26.7%)
of 60 patients who were initially seronegative and could be followed
up after the bite of an infected tick. These results indicate that
the transmission rate from infected ticks in Europe is higher than
previously assumed. Examination of ticks and antibiotic prophylaxis in
the case of positivity appear to be indicated.



=====*=====


III.  J NEUROL NEUROSURG PSYCHIATRY: Differential diagnosis of multiple
     sclerosis: contribution of magnetic resonance techniques.
------------------------------------------------------------------------
AUTHORS: Triulzi F, Scotti G
ORGANIZATION: Department of Neuroradiology, Scientific Institute H S
             Raffaele, Milan, Italy. triulzi.fabio@hsr.it
REFERENCE: J Neurol Neurosurg Psychiatry 1998 May;64 Suppl 1:S6-14
ABSTRACT:


It is widely accepted that magnetic resonance imaging (MRI) findings
are not totally specific for the diagnosis of multiple sclerosis.
White matter lesions that mimic those of multiple sclerosis may be
detected in both normal volunteers and patients harbouring different
diseases. Virtually all the characteristic features of multiple
sclerosis are sometimes encountered in other conditions affecting
predominantly the white matter. Different conditions such as
vasculitis, subcortical atherosclerotic leukoencephalopathy, Lyme
disease, or acute disseminated encephalomyelitis can be virtually
indistinguishable from multiple sclerosis on conventional MR images.
Also the FLAIR technique adds little to the differential diagnosis.
The calculation of magnetisation transfer ratio (MT ratio) may be
useful to better characterise some entities, such as vasculitis, from
multiple sclerosis.



=====*=====


IV.   N ENG J MED: Persistent parasitemia after acute babesiosis.
-----------------------------------------------------------------
AUTHORS: Krause PJ, Spielman A, Telford SR 3rd, Sikand VK, McKay K
        Christianson D, Pollack RJ, Brassard P, Magera J, Ryan R,
        Persing DH
ORGANIZATION: Department of Pediatrics, Connecticut Children's Medical
             Center and University of Connecticut School of Medicine,
             Hartford CT 06106, USA.
REFERENCE: N Engl J Med 1998 Jul 16;339(3):160-5
ABSTRACT:


BACKGROUND: Babesiosis, a zoonosis caused by the protozoan Babesia
microti, is usually not treated when the symptoms are mild, because
the parasitemia appears to be transient. However, the microscopical
methods used to diagnose this infection are insensitive, and few
infected people have been followed longitudinally. We compared the
duration of parasitemia in people who had received specific
antibabesial therapy with that in silently infected people who had not
been treated.
METHODS: Forty-six babesia-infected subjects were identified from 1991
through 1996 in a prospective, community-based study designed to
detect episodes of illness and of seroconversion among the residents
of southeastern Connecticut and Block Island, Rhode Island. Subjects
with acute babesial illness were monitored every 3 months for up to
27 months by means of thin blood smears, Bab. microti polymerase-chain-
reaction assays, serologic tests, and questionnaires.
RESULTS: Babesial DNA persisted in the blood for a mean of 82 days in

24 infected subjects without specific symptoms who received no specific
therapy. Babesial DNA persisted for 16 days in 22 acutely ill subjects
who received clindamycin and quinine therapy (P=0.03), of whom 9 had
side effects from the treatment. Among the subjects who did not
receive specific therapy, symptoms of babesiosis persisted for a mean
of 114 days in five subjects with babesial DNA present for 3 or more
months and for only 15 days in seven others in whom the DNA was
detectable for less than 3 months (P<0.05); one subject had
recrudescent disease after two years.
CONCLUSIONS: When left untreated, silent babesial infection may
persist for months or even years. Although treatment with clindamycin
and quinine reduces the duration of parasitemia, infection may still
persist and recrudesce and side effects are common. Improved
treatments are needed.



=====*=====


V.    EPIDEMIOL MIKROBIOL IMUNOL: Educational status of the Czech
     population about Lyme borreliosis and experience with tick bites
----------------------------------------------------------------------
AUTHORS: Basta J, Janovska D, Daniel M
ORGANIZATION: Statni zdravotni, ustav, Praha, Czech Republic
REFERENCE: Epidemiol Mikrobiol Imunol 1998 Apr;47(2):52-5
ABSTRACT:


The incidence of Lyme borreliosis (LB) has a rising trend since 1995.
In 1995 6,302 cases were reported, in 1996 4,192 (EPIDAT, SZU). The
objective of the present work was to assess in a selected population
sample knowledge of ticks and their relationship to Lyme borreliosis.
The investigation was based on a survey using questionnaires. 110
respondents were selected according to the following pattern: 19
secondary school students, 32 blood donors, 44 visitors of parks, 15
countryside people.  99.1% of the subjects knew about the existence
of ticks in the Czech Republic, 10.9% of the respondents do not know
about Lyme borreliosis. More than 80% of the people are in the
countryside at least once a week. 87% of the people report they had a
tick, 75% removed a tick from another person. Only 6.7% of the
respondents never had any contact with ticks. When removing ticks
17% of the subjects use disinfection, 67% use oil. Almost 30% of the
respondents remove ticks with bare hands and more than 14% destroy

them by squashing them between their fingers. 41% are not aware of
the risk of transmission of tick-borne encephalitis.  From the
investigation a frequent contact of the population with ticks is
apparent. Theoretical knowledge of the problem is extensive, practical
experience is different. Unfortunately unsuitable habits in removal of
ticks persist and this increases the risk of transmission of Lyme
borreliosis.



=====*=====


IV.   ABOUT THE LYMENET NEWSLETTER
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