Lyme rashes, as shown
here, will be seen only 50 to 60% of the time.
What is Lyme
disease? Lyme disease is the most prevalent tick-associated disease
in the United States. Thousands of human cases are reported annually, mainly
in northeastern and upper midwestern regions of the country. The blacklegged
tick (Ixodes scapularis), formerly known as Ixodes dammini and sometimes
referred to as the deer tick, is the most important species that transmits
the bacterial disease agent. Lyme disease is a zoonatic infection
caused by Borrelia burgdorferi. It is caused by a type of bacterium called
a spirochete, which are spiral or corkscrew in shape.
An infected tick can transmit the spirochetes to the humans and animals
it bites. There is some debate to whether other bugs, such as mosquitos
or fleas can transmit Lyme, or if it is sexually transmitted, however it
is transmitted in utero. Lyme is a multi systemic inflammatory infection,
and if left untreated it will travel from your skin, through the bloodstream,
joints, organs, and will establish itself in various body tissues, and
can cause a number of symptoms including neuropsychiatric manifestations.
It is very important to treat as quickly as possible. If you know
bit by a tick or start experiencing
any symptoms of Lyme disease, you should see your doctor right away, don't
wait! It could be the difference between acute Lyme and Chronic Neuroborreliosis.
The highest incident of Lyme disease is reported between the months of
May and September when the nymphal state of the black legged tick is active.
Lyme disease is a great masquerader,
which makes getting a proper diagnosis of Lyme a real challenge. Lyme can
cause symptoms in multiple organs, including skin, heart, nervous system,
joints and muscles and gastrointestinal tract. Involvement of the
lungs, eyes or urinary tract has also been reported. For some people,
fatigue or brain fog is the only symptom of Lyme disease. Sometimes the
most prominent symptom is a change in mood or personality.
Symptoms may begin days or months
after a tick bite. Many victims of Lyme disease are unaware of having had
a tick bite. In approximately 50 to 60% of the cases, the classic
"bull's eye rash" will develop, which can be an early sign of the disease.
Doctors usually use blood tests to make a diagnosis of Lyme disease, but
several factors limit their value:
These tests rely on antibodies, proteins made by your immune system to
attack Borrelia. Antibodies
be measurable for a month after the tick bite.
* Early treatment with antibiotics may prevent antibody formation without
curing Lyme disease.
* People who are immune suppressed may not make antibodies.
* The results of antibody testing at different labs can vary greatly.
* Deer ticks may carry pathogenic microbes other than Borrelia. These other
infections will not be detected by a test for Lyme disease but may produce
distinct illnesses like babesiosis, ehrlichiosis or bartonellosis that
overlap symptomatically with Lyme disease.
is a complex cycle involving ticks, mice and deer. The primary reservoir
of B. burgdorferi
mainly the white footed mouse. Infection is transmitted by the deer
tick (black legged tick) Ixodes scapularis. Other Ixodes species are responsible
for transmission as well in various parts of the United States, Europe
and Asia. The tick has a four stages: egg, larva, nymph and adult.
The larvae, nymphs and adults feed only once and slowly, requiring 3 to
5 days to injest the blood, depending on the stage of the tick. Larvae
are rarley infected with B. burgdorferi. Larvae and nymphs typically
become infected with Lyme disease bacteria when they feed on the infected
white footed mice, chipmunks, or certain species of birds. People
aquire Lyme disease mainly from the nymph (which survive on mice and other
rodents) because they are active during the time of year when people are
in there ecosystem such as walking through brush or tall grass. Because
the nymph is the size of a small freckle or poppy seed, it often is not
detected and remains attached from 36-48 hours, the period that is required
to transmit infection. Less than half the cases of Lyme disease will
ever develop the “ Bulls Eye” rash leaving the bitten person to have no
idea it ever happened. As the tick feeds, spirochetes escape from
the salivary gland of the insect into the skin of the human host.
The white footed
mouse is the principal source (reservoir) of B. burgdorferi, Babesia microti,
the agent of human babesiosis in the east, and the agent of human granulocytic
ehrlichiosis. White tailed deer and other large mammals are the primary
host for the adult tick and are essential to the mating and survival of
the tick. Deer are not reservoirs for Lyme disease. The female
tick can lay around 2,000 eggs or more where larvae starts the beginning
of the life cycle. Birds can be a host for Ixodes scapularis and have been
implicated in long distance dispersion.
Nymph tick shown here
There are three stages to Lyme
Early localized infection (The first
Bull’s eye rash (erythema migrans) The
rash is usually circular and has a fading spot in the center. 50 to 60%
of the people infected will develop a rash. Note: Some people will
never have any symptoms in this stage.
Flu like symptoms (Usually the first
Muscle and joint pain
Swollen lymph nodes
Early disseminated infection (1 to
If Lyme disease is not detected and
treated while early symptoms are present, the infection may disseminate
and affect the skin, joints, organs, nervous system, and heart.
Late persistent infection, late disseminated
Migrating pain (pain that changes locations
and comes and goes)
Weakness and/or numbness in the arms
Severe and recurring headaches
Fainting or vaso vagal attacks
Poor memory and concentration problems
Irritability Vision problem
Internal buzzing feeling
This is just
a generalized short list of symptoms. Lyme disease can cause almost any
symptom because it is a multi systemic disease. It can travel anywhere
including your central nervous system (spine and brain). One of the common
complaints of patients with Lyme disease is that the symptoms come and
go and change locations frequently. You can take a group of several
people infected with Lyme, and all might be experiencing different symptoms.
The time frames of each stage are generalized also. Each patient moves
through these stages at different timing. One person may not show
symptoms for several months while another may get stage three symptoms
Swelling and pain in the joints
Numbness and tingling in the extremities
Bells Palsy (partial paralysis of the
Getting lost in familiar places
Word retrieval problems,
Migrating pain and symptoms
Tinnitus, ear ringing or feeling of fullness
Shortness of breath
Rib and sternum soreness
Upset stomach and GI problems
Burning and stabbing pains
It all depends on strains, co-infections, and your own immune system.
to “typical” Lyme disease, there are also co-infections. These other
tick borne illnesses added to the Lyme disease can result in more severe
disease as well as complications in treatment. Below is a sample of the
types of co-infections.
are bacteria that live inside cells; they can infect humans, mammals, and
a wide range of wild animals. Not all Bartonella species cause disease
in humans. Bartonella henselae causes an important emerging infection first
reported in 1990 and described as a new species in 1992. It is mainly carried
by cats and causes cat scratch disease, endocarditis, and several other
serious diseases in humans. Bartonella bacteria are known to be carried
by fleas, body lice and ticks. Scientists suspect that ticks are a source
of infection in some human cases of bartonellosis. People with tick bites
and no known exposure to cats have acquired the disease. People who recall
being bitten by ticks have been co-infected with Lyme and Bartonella. More
research needs to be done to establish the role of ticks in spreading the
can be anywhere from mild to serious. Early signs are fever, fatigue, headache,
sore soles of feet, poor appetite, abnormal liver enzymes, encephalopathy,
endocarditis, flu-like malaise, hemolysis with anemia, hepatomegaly, immune
deficiency, jaundice, lymphadenopathy, myalgias, myocarditis, sore throat,
splenomegaly, weakened immune response, and an unusual, streaked rash.
Swollen glands are typical, especially around the head, neck and arms.
is an infection caused by a malaria like parasite, also called a “piroplasm,”
that infects red blood cells. Babesia microti is believed to be the most
common piroplasm infecting humans, but scientists have identified over
twenty piroplasms carried by ticks. Ticks may carry only Babesia or they
may be infected with both Babesia and Lyme spirochetes. People can also
get babesiosis from a contaminated blood transfusion. Babesia likes
red blood cells. Once it enters a red blood cell, the protozoa split
in half to form two new protozoa. This splitting continues until
there are too many protozoa inside the cell. The cell then bursts
and releases the micro-organisms into the blood. Then the released
protozoan find new blood cells to enter to further reproduce.
everyone who contracts this disease gets flu-like symptoms of fever and
chills. Other symptoms are generalized weakness, gastrointestinal symptoms,
nausea, drenching night sweats, muscle aches, vomiting, diarrhea, and stomach
pain. As Babesia causes your red blood cells to rupture you will begin
getting symptoms like jaundice, dark urine, shortness of breath, pain in
your extremities, and a swollen spleen.
is an infectious disease transmitted by the bite of a tick. It is caused
by bacteria that belong to the family called Rickettsiae. Rickettsial bacteria
cause a number of serious diseases, including Rocky Mountain spotted fever
and typhus. All of these diseases are spread to humans by a tick, flea,
or bites from mites. There are two kinds of ehrlichiosis, both of which
are caused by tick borne Rickettsial parasites called Ehrlichia that infect
different kinds of white blood cells. In HME (human monocytic ehrlichiosis),
they infect monocytes. In HGE (human granulocytic ehrlichiosis), they infect
granulocytes. HGE was renamed anaplasmosis in 2003. Ticks carry many Ehrlichia-like
parasites that have not been identified yet. It is likely that the lone
star tick transmits HME and that the deer tick transmits HGE.
of Ehrlichia are flu like symptoms, chills, fever, elevated liver enzymes,
headaches, myalgias, fatigue, persistent leukopenia, thrombocytopenia,
petechia (pin head size red dots), and a flat rash.
Mycoplasma:The most common
of the Lyme Co-infection is Mycoplasma Fermentans. It is the smallest of
bacteria’s and has the ability to enter any cell and alter itself, changing
its cellular makeup with every cell division. It invades all systems of
the human body.
Symptoms: Flu-like aches
and pains, cramps and spasms night sweats, intermittent fevers, memory
loss, depression, irritability, loss of concentration, nervousness, anxiety,
gastrointestinal, problems, nausea. Mycoplasma are a heterogeneous
group of the smallest organisms capable of self replication. They can cause
a wide variety of diseases in animals. Some mycoplasmas cause respiratory
or urogenital diseases in humans. Mycoplasmas often chronically colonize
our respiratory and urogenital tracts without apparent clinical significance.
told that nymphal ticks are the size of a poppy seed.
Can you find
the tick among the seeds on this bagel?
Biofilms: A New Hideout for Borrelia
Eva Sapi Ph.D.
University of New Haven
Department of Biology and Environmental
Dodds Hall 314
300 Boston Post Road, West
Haven CT 06516
Telephone: (203) 479-4552
The University of New Haven established
a Lyme Disease Research group six years ago. To date, over forty graduate
students have received training in Lyme disease related research. One of
our recent projects studies the different formations of Borrelia burgdorferi,
the Lyme disease bacteria. With coauthor Dr. Alan MacDonald, we recently
suggested that Borrelia burgdorferi is capable of forming an organized
structure called biofilm1. Our proposal is based on recently published2
and several unpublished images of Borrelia. Those images, like the image
presented in this article (Figure 1) show structures that strongly resemble
What is a biofilm? “Biofilm is a self-made
protective environment for microbial populations in which they adhere to
each other or to living or inert surfaces”. In the biofilm, single or multiple
types of organisms can surround themselves with a complex matrix, better
known as “slime” 3-4. The main purpose of the biofilm structure is to allow
microbes to survive various environmental stresses, including the presence
of attacking immune cells like phagocytes, or antibacterial agents. While
conventional antibiotic therapy is usually effective against free floating
bacteria, it is frequently ineffective once pathogens have formed biofilms,
because biofilm colonies can be up to 1,000-times more resistant to antibiotics.
Furthermore, even if a biofilm related
infection appears to respond to antibiotics, it could relapse weeks or
even months later and turn into a very difficult to treat chronic infection.
The National Institutes of Health estimate that nearly 80 percent of chronic
microbial infections in the human body are due to biofilms, such as chronic
lung infection in cystic fibrosis patients, catheter infections, chronic
urinary and middle ear infections, gingivitis, sinusitis and even fatal
What do we know about biofilm? Biofilms
start as just a few microorganisms adhering to each other or to a surface,
and then begin to communicate3-4. This communication will initiate a change
in gene expression and cells start to produce an exopolysaccharide, which
will become the protective matrix 3. The colonies then can develop
into complex, three dimensional structures housing millions of individual
microbes. Like cities, they have towers, columns, bridges and channels
for the flow of nutrients.
A mature biofilm is usually composed
of three layers: an inside film layer that binds the biofilm to the surface;
another film made up of colonies of single or multiple species of bacterial
and/or fungal organisms; and the surface film from which free floating
microorganisms can be released as individual cells that can colonizing
So what are the mechanisms by which
bacteria can evade the therapeutic interventions in biofilm? The first
studies suggested that the bacteria deep within the biofilm live in an
environment where diffusion of antibiotics might be difficult. There are
major differences in the chemical composition of the biofilm such as low
pH and anaerobic condition etc., which can either inactivate the antibiotics
or render bacteria inactive so the antibiotics cannot kill them6.
However, recent publications suggested
that the main reason for antibiotics resistance is the changes in the gene
expression profile of microbial cells harboring in biofilms. For example,
researchers identified mutant bacteria that are capable of forming biofilm
but are not resistant to antibiotics7. The differential expression of a
large number of genes is known to occur in the initial steps of biofilm
formation8, such as the upregulation of exopolysaccharide synthesis9.
So how about the immune system? Why
can’t they recognize and destroy the biofilm? Multiple studies demonstrate
that phagocytes can be found attached to biofilm but they are not able
to eliminate it3. To answer this very puzzling question German scientists
used marine bacteria as a model and studied the defensive mechanism against
their environmental enemy, which is a phagocyte (called amoebae). They
identified that this marine bacterial biofilm can release a paralyzing
agent that deactivates and even kills the amoeba10. So clearly biofilm
is not just a defensive fortress, it can also fight back.
So how about chronic Lyme disease?
Can it be explained by a biofilm formation of Borrelia burgdorferi? If
yes, the possibility that Borrelia burgdorferi is capable of forming a
biofilm can change the way we think about Lyme disease, especially in patients
where it seems to be a persistent disease, despite long term antibiotic
treatment11. The elucidation of the molecular mechanisms responsible for
the switch from free living growth to a biofilm phenotype, with the development
of antibiotic resistance, should provide novel therapeutic targets in chronic
Despite the potential importance of
this hypothesis, to date there has been no studies attempted to determine
whether Borrelia burgdorferi is indeed capable of biofilm formation and
whether such a formation results in increased antibiotic resistance. Borrelia
burgdorferi sensitivity to antimicrobial agents has traditionally been
studied in the free-living state12. Conclusions drawn from many of these
studies, therefore, need to be revalidated.
We have recently established an in
vitro model to study biofilm formation of Borrelia burgdorferi and proposed
use this system to evaluate the antimicrobial
sensitivity of Borrelia burgdorferi in biofilm. Our goal is to test several
known antibiotic agents frequently used in the Lyme disease treatment,
as well as several natural agents, for the ability to interfere with or
destroy biofilm production.
As mentioned above, the formation
of a biofilm begins with the attachment of free floating microorganisms
to each other or to a surface. In the case of Borrelia burgdorferi, our
preliminary results show that Borrelia burgdorferi is capable of forming
biofilm. Figure 1 shows a dense culture of Borrelia spirochete surrounded
by a very dominant matrix. In this protective matrix, Borrelia burgdorferi
can be found in spirochete and cystic form.
We have monitored several environmental
conditions for the initiation of biofilm structure and found that that
cell density is one of the most important factors. When Borrelia burgdorferi
reach a certain density, they started to “stick” to each other and start
to form an organized structure. Our working hypothesis for this finding
is that nutrient depletion is the main stress factor for the initiation
It was previously demonstrated that
organisms within biofilms could withstand nutrient deprivation better than
free-floating counterparts3. Furthermore, as we presented at the 2007 ILADS
conference, we have seen similar changes after exposure of Borrelia burgdorferi
to penicillin. In the penicillin treated samples, as early as 24h, we observed
formation of a granual/cystic form covered by a biofilm like substance13.
In our next set of experiments we
will test other stressors that can initiate Borrelia burgdorferi biofilm
formation, including different temperatures, pH, oxidative radicals, heavy
metals and of course several synthetic and natural antibacterial agents.
Our final goal is to identify antibacterial agents that are effective in
killing Borrelia burgdorferi without inducing biofilm, or even capable
of destroying Borrelia burgdorferi in biofilm.
In summary, if we can demonstrate
that biofilm structure of Borrelia burgdorferi renders them resistant to
antibiotics, it could provide a logical explanation as to why extensive
antibiotic treatment for patients with a tick bite history could fail.
The end result from our study could provide novel therapeutic approaches
for Lyme literate physicians to explore for chronically ill patients.
Ticks compared to a dime