What makes Lyme disease such a medical challenge?
Description: What makes Lyme disease such a medical challenge? Holly Ahern MS, MT(ASCP) Associate Professor of Microbiology SUNY Adirondack, Queensbury, NY ahernhsunyacc.edu Lyme Disease A Tick-borne Spirochetosis? Lyme disease in humans was first
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slide1. What makes Lyme disease such a medical challenge? Holly Ahern MS, MT(ASCP)
Associate Professor of Microbiology
SUNY Adirondack, Queensbury, NY
ahernh@sunyacc.edu<br>
slide2. Lyme Disease – A Tick-borne Spirochetosis? 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.<br>
slide3. Borrelia are not like other bacteria… Other Bacteria
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 long-lasting immunity. Borrelia
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<br>
slide4. Lyme disease is not like other diseases caused by bacteria Other Bacterial Diseases
Disease is apparent with a defined beginning and end
Clear and characteristic “signs” and “symptoms”
Accurate diagnostic tests are available
Antibiotics are a very effective treatment because the bacteria are reproducing Lyme disease
Disease may not always be apparent and timeline varies
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<br>
slide5. Relationships between Borrelia and hosts are complicated They have a “life cycle” that involves animals and ticks.
Exceptional, well adapted animal commensals that cause persistent BUT NOT DISEASE INDUCING infection in their “reservoir” host (mice in our area).
Partner with blood sucking insects (ticks) to get transmitted to new host animals (including us).
Long-lived animals (like us) with strong adaptive immunity experience symptoms of disease but no sterilizing immunity
Disease symptoms are due largely to infection-associated inflammation<br>
slide6. Borrelia live a complicated life Genome is more complex than any other bacteria
One chromosome, multiple plasmids.
Vary gene expression depending on environment
Exchange genes with other Borrelia
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” A B C<br>
slide7. Our immune system responds to the same Borrelia in different ways Borrelia spirochetes Spirochetes forming “round bodies” Round body “persisters” Biofilm of Borrelia<br>
slide8. Why blood tests for Lyme disease don’t work Current “gold standard” blood tests detect immune system response to infection, NOT the infection itself.
Bacteria 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 Accuracy of this test is <50%<br>
slide9. Why a standard antibiotic treatment approach doesn’t always work Antibiotic dose required to kill bacteria in biofilm for is 1,000 – 5,000 times higher than for motile forms.
Pleomorphic forms (called cysts or round bodies or persisters) are antibiotic tolerant
They slow their rate of growth
They become dormant “persisters” with no reproduction
Remove antibiotic challenge, growth rate speeds up and/or persisters reactivate causing recurrence of symptoms<br>
slide10. 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???<br>
slide11. What we NEED: 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
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
Ways to prevent tick bites in the first place!
Oral vaccine in pellets for mice
Chemical and biological treatments; environment and personal protection
LEADERSHIP from US and State reps
Public Health Policies for Lyme disease MUST BE CHANGED!<br>
Associate Professor of Microbiology
SUNY Adirondack, Queensbury, NY
ahernh@sunyacc.edu<br>
slide2. Lyme Disease – A Tick-borne Spirochetosis? 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.<br>
slide3. Borrelia are not like other bacteria… Other Bacteria
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 long-lasting immunity. Borrelia
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<br>
slide4. Lyme disease is not like other diseases caused by bacteria Other Bacterial Diseases
Disease is apparent with a defined beginning and end
Clear and characteristic “signs” and “symptoms”
Accurate diagnostic tests are available
Antibiotics are a very effective treatment because the bacteria are reproducing Lyme disease
Disease may not always be apparent and timeline varies
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<br>
slide5. Relationships between Borrelia and hosts are complicated They have a “life cycle” that involves animals and ticks.
Exceptional, well adapted animal commensals that cause persistent BUT NOT DISEASE INDUCING infection in their “reservoir” host (mice in our area).
Partner with blood sucking insects (ticks) to get transmitted to new host animals (including us).
Long-lived animals (like us) with strong adaptive immunity experience symptoms of disease but no sterilizing immunity
Disease symptoms are due largely to infection-associated inflammation<br>
slide6. Borrelia live a complicated life Genome is more complex than any other bacteria
One chromosome, multiple plasmids.
Vary gene expression depending on environment
Exchange genes with other Borrelia
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” A B C<br>
slide7. Our immune system responds to the same Borrelia in different ways Borrelia spirochetes Spirochetes forming “round bodies” Round body “persisters” Biofilm of Borrelia<br>
slide8. Why blood tests for Lyme disease don’t work Current “gold standard” blood tests detect immune system response to infection, NOT the infection itself.
Bacteria 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 Accuracy of this test is <50%<br>
slide9. Why a standard antibiotic treatment approach doesn’t always work Antibiotic dose required to kill bacteria in biofilm for is 1,000 – 5,000 times higher than for motile forms.
Pleomorphic forms (called cysts or round bodies or persisters) are antibiotic tolerant
They slow their rate of growth
They become dormant “persisters” with no reproduction
Remove antibiotic challenge, growth rate speeds up and/or persisters reactivate causing recurrence of symptoms<br>
slide10. 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???<br>
slide11. What we NEED: 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
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
Ways to prevent tick bites in the first place!
Oral vaccine in pellets for mice
Chemical and biological treatments; environment and personal protection
LEADERSHIP from US and State reps
Public Health Policies for Lyme disease MUST BE CHANGED!<br>