Download Why Lyme disease is a medical challenge

What makes Lyme disease
such a medical challenge?
Holly Ahern MS, MT(ASCP)
Associate Professor of Microbiology
SUNY Adirondack, Queensbury, NY
[email protected]
Lyme Disease – A Tick-borne Spirochetosis?
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Lyme disease in humans was first described in
1977 as an “epidemic of arthritis” preceded by
a rash.
Dr. Wilhelm Burgdorfer dissected ticks from
Shelter Island NY and found them to be full of
microbes.
Burgdorfer showed that one of them, a
spirochete in the genus Borrelia, caused the
same type of disease when rabbits were
infected.
The spirochete was named Borrelia
burgdorferi, and this sole bacterium is STILL
considered the one and only cause of “Lyme
disease” in the United States.
Borrelia are not like other bacteria…
Other Bacteria
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May survive outside a host
Reproduce rapidly and grow
to large numbers
Have an arsenal of
sophisticated weaponry
Engage the host immune
system
Induce strong and longlasting immunity.
Borrelia
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Can’t survive without a host
Reproduce slowly and sometimes
don’t reproduce at all.
Lack classic bacterial weaponry
like toxins or enzymes.
Evade or subvert the host
immune system
Seldom induce strong or long
lasting immunity
Lyme disease is not like other diseases
caused by bacteria
Other Bacterial Diseases
Lyme disease
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Disease is apparent with a
defined beginning and end
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Disease may not always be
apparent and timeline varies
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Clear and characteristic
“signs” and “symptoms”
Accurate diagnostic tests are
available
Antibiotics are a very
effective treatment because
the bacteria are
reproducing
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Multi-system disease that
isn’t always the same
Diagnostic test endorsed by
the CDC is only 50% accurate
Antibiotics are not always
effective because Borrelia
are antibiotic tolerant
bacteria
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Relationships between Borrelia and hosts are
complicated
They have a “life cycle” that involves
animals and ticks.
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Exceptional, well adapted animal commensals that
cause persistent BUT NOT DISEASE INDUCING infection
in their “reservoir” host (mice in our area).
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Partner with blood sucking insects (ticks) to get
transmitted to new host animals (including us).
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Long-lived animals (like us) with strong adaptive
immunity experience symptoms of disease but no
sterilizing immunity
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Disease symptoms are due largely to infectionassociated inflammation
Borrelia live a complicated life
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Genome is more complex than any other bacteria
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One chromosome, multiple plasmids.
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Vary gene expression depending on environment
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Exchange genes with other Borrelia
A
B
Genetic variation leads to ongoing evolution of new
genospecies of Borrelia – which ones actually
“cause” Lyme disease?
Cells change over time (“pleomorphic”)
A. Spirochete (twisted rod) is motile and swims
B. Non-motile forms produce a “BIOFILM”
C. Twisted form balls up into a rounded form which stop
eating and reproducing, become antibiotic tolerant
“persisters”
C
Our immune system
responds to the same
Borrelia in different ways
Borrelia spirochetes
Round body
“persisters”
Spirochetes forming
“round bodies”
Biofilm of Borrelia
Why blood tests for Lyme disease don’t work
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Current “gold standard” blood
tests detect immune system
response to infection, NOT the
infection itself.
 Bacteria
Accuracy
of this test
is <50%
shut down antibody
production by disrupting “germinal
centers” in lymph nodes.
 Borrelia changes its surface antigens
to trick the immune system.
 Other Borrelia species cause Lyme
disease or “Lyme-like” disease. Blood
tests are specific for ONLY the
SPIROCHETE FORM of B. burgdorferi
Why a standard antibiotic treatment approach
doesn’t always work
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Antibiotic dose required to kill bacteria in biofilm for
is 1,000 – 5,000 times higher than for motile forms.
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Pleomorphic forms (called cysts or round bodies or
persisters) are antibiotic tolerant
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slow their rate of growth
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become dormant “persisters” with no reproduction
Remove antibiotic challenge, growth rate speeds up
and/or persisters reactivate causing recurrence of
symptoms
So, what does
work?
• Thanks to funding from
non-profit organizations,
research to identify
antimicrobial agents
effective against Borrelia
spirochetes and persisters
is finally underway
• Congress – NIH and CDC
are federal agencies
funded by tax dollars. Why
isn’t more being done???
What we NEED:
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An accurate diagnostic test for all known tick-borne diseases
Better rate of accuracy (>50%)
 Detects actual presence of bacteria
 Based on genomic analysis – detects DNA or RNA from more than just Borrelia burgdorferi
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Better treatment approaches, for tick bite AND BEYOND
Identify new antimicrobial drugs that work against Borrelia persisters
 Identify new approaches that work against bacterial biofilms
 Investigate how Borrelia infection evades and disables the immune system
 STOP MARGINALIZING PATIENTS WHO DON’T RECOVER AFTER 2 WEEKS OF ANTIBIOTICS
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Ways to prevent tick bites in the first place!
Oral vaccine in pellets for mice
 Chemical and biological treatments; environment and personal protection
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LEADERSHIP from US and State reps
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Public Health Policies for Lyme disease MUST BE CHANGED!