Category Archives: Treatments

Activities that support recovery that are not supplements or medications

Bioresonance Treatment Overview

Many people who are dissatisfied with a lack of progress on antibiotics and pharmaceutical (allopathic) medicines are considering Naturopathic and Integrative (Multiple) medicine for treatment. Energy Medicine (Generic name covering several technologies) is becoming popular for the treatment of Lyme disease and co-infections yet little is known about many of the options that exist.

This post provides an overview of the treatements we have encountered.

Bioresonance Therapy

Bioresonance machines allow a therapist to determine pathogens and stressors on the body to help select the most appropriate treatments, ensuring that the body’s elimination organs are built up to support the removal of toxins before Pathogens are removed. In many cases, by just unblocking the elimination organs (Liver, kidneys, Lymph nodes, connective tissue)  and boosting the immune system the body is able to clear many of the pathogens  naturally without treatment.Bioresonance machines cost up to £20,000, so most are purchased by therapists who offer treatments to patients typically charging £70-100 per hour.  A growing number of patients are purchasing Bioresonance machines for home use under the guidance of a trained therapist. A second-hand machine can be obtained for £5-10,000. A key benefit of Bioresonance Therapy is that you don’t need to learn how to use a complex machine before seeing benefits.

When surveyed in May  2016, 10 Bioresonance therapists from the UK, US, Germany & Holland reported that they have been able to eliminate Lyme disease in more than 70% of patients and reduce the symptoms in many the remaining 30%. One experienced US based therapist states that 30% of her Lyme patients don’t improve with the elimination of Lyme disease bacteria and that this is typically due to an undetected virus (mostly Herpes family) that cause symptoms that were assumed to be Lyme disease.

Bioresonance machines can be diagnostic or therapy only and sometimes they are combined into one unit, such as BICOM product (above) from German company Regumed.

Diagnostic Testing can be carried out on hundreds of pathogens very quickly. There are several approaches including the use of glass ampules and digitally encoded ampules (containing the resonant frequency of pathogens). The BICOM machine inverts the pathonogenic frequency  into a treatment which can be tested to confirm a “beneficial treatment” using heart rate variability monitoring, Keniesiology (muscle testing) or using a biofeedback device called a biotensor. Bioresonance testing is both fast, cheap and reliable with no waiting around for test results.

BIORESONANCE therapy can achieve major benefits in just two or three treatments. It is possible to use as a home treatment device with a few hours training. Less treatment is required compared to RIFE therapy and it’s thought to be more effective on a wider range of co-infections. A therapist will typically combine multiple treatment options into one treatment session. Further information on Bioresonance can be found here.

Some therapists combine Bioresonance therapy with Oxygen, Ozone, Biophoton therapy along with naturopathic treatments, supplements and herbs.

A novel approach used by some patients is to combine the use of both energy medicines with visits to a Bioresonance Therapist and regular RIFE treatments at home in between.

Some patients who have have been on pharmaceuticals for many years and are very weak may not be able to obtain a full recovery with Bioresonance treatment, but are likely to obtain some benefit.

A list of UK and European therapists offering Energy Medicine therapies will be made available shortly.

Figure 1. An older BICOM 2000 from Regumed

bicom-2000

BICOM Picture 1

Bioresonance therapy is one of a number of procedures including homeopathy, acupuncture and other naturopathic procedures within the area of empirical healing.

The fundamental principles of the following hypothesis for bioresonance therapy have been confirmed by the latest discoveries in quantum mechanics and biophysics, but have not yet been accepted by current expert opinion within orthodox medicine.

The BICOM machine does not typically cause severe Herxeimer reactions so a patient can receive 3-5 treatments per week, although typically it’s one or two sessions per week as it can take several days to fully absorb the treatment.

Wave-particle duality

Discoveries made in quantum physics have revealed that all particles of matter share the characteristics of both waves and particles. This means that all substances – and therefore all cells, parts of the body, as well as viruses, bacteria, pollen, toxins, etc. – emit electromagnetic waves. Depending upon their nature, all substances have a quite specific typical wavelength or frequency with highly individual characteristics. This is known as a frequency pattern.

cells and matter

Cells communicate with one another

Living as we do in the communication and information age, it is time we faced up to the fact that the body can only function and regulate itself because communication and thus an exchange of information takes place between the various cells in the body. Research into biophotons is based on the assumption that cells communicate with one another by means of “flashes of light” (photon radiation). They exchange information over certain frequencies.

This information exchange functions unhindered in healthy bodies. As a result, each cell and each part of the body is able to do its job.

2 cells communicating via electro-magnetic frequencies

Stress-inducing factors or substances can impede communication between cells

If, however, undesirable substances (toxins, viruses, bacteria, etc.) or harmful radiation act on the body, these may impede communication between the cells.

pathogenic cell communication interrupts normal cell

Disrupted cell communication may result in organic changes

Where communication between cells is impaired, this will of course prevent those cells from functioning properly and we see evidence of this to varying degrees in the form of non-specific disturbances in general well-being, poor performance, chronic fatigue and later as organic changes plus related symptoms.

Symptoms frequently occur at the point where there was already a deficiency – often hereditary.

 

sick cells

Determining individual stresses accurately

The body’s extracellular fluid is not just the cells’ culture medium. It also serves as a “special rubbish dump” for harmful substances if the eliminating organs such as the liver/gallbladder, kidneys, intestines, etc. are overloaded. Since water is also an excellent store of information, information from harmful substances is also stored here however. This area is not easily accessible to laboratory procedures. These stresses can usually be tested very quickly and painlessly at the biophysical level. The Bicom device offers a valuable tool in this respect. In many cases it is possible to discover which stresses may cause health problems in the patient (e.g. bacteria, viruses, electronic smog, dental materials, allergens, etc.).

The stresses identified are treated with the appropriate frequency patterns using the BICOM device

The body’s own regulatory system can be supported and aided to a considerable extent by BICOM bioresonance therapy

healthy cell communication restored

Communication between the cells can take place once again unimpeded. Harmful substances can be released and excreted.

Frequency Patterns are stores in small glass ampules shown below. The Ampules are used for Testing the existence of a Pathogen and can also be used to eliminate the pathogen. The frequency pattern can also be digitized and stored in a software program so many therapists use a combination of glass and digital ampules.

A Therapist treating a complex illness like Lyme & Co-infections will typically have 500 or over 1000 ampules to understand why a patient is unwell. IT’s also possible to treat the patient without knowing what pathogens are affecting them by using their blood as a treatement, reversing the frequencies of pathogens found by the BICOM machine.

 

Bionic 880 The Photon Therapy 

bionic 880

This German medical device has been getting great reviews as it appears to force extracellular bacteria out of the cells so that the immune system can find and eliminate them. This machine causes Herxeimer reactions so treatment intensity must be built up to prevent toxins overloading the elimination organs.

The Bionic 880 uses pulsating Infra Red (IR) light, which can activate and regulate many metabolic processes. Light or Photon energy plays an extremely important role  to release  substances such as enzymes, prostaglandin, lymphocytes and hormones to heal and repair the body’s damaged cells. 

The radiated Photons are first absorbed by the skin, which multiply in the body and then spread into the brain and branch to the Nervous System (NS) as well as the spinal cord and harmonize the production of hormones e.g. endorphins (pain hormones) serotonin (appetite and mood hormone), cortisol (stress hormone) etc.

Many German doctors have used the Photon Therapy for the last 10 years. It is very popular therapy in Germany. Bionic 880 is a medical device and certified by German Medical Authority.

Bionic 880 is effective method of therapy. It is gentle, fast acting and totally free of side effects. It   could be used on adults as well as children for various conditions. It enhances the quality of life.

The treatment

It is a painless procedure and lasts for 30 to 45 minutes. The radiation head is simply positioned onto different locations of the body (meridians, acupuncture points and effected areas) to distribute the photons, which enhances the production of hormones, prostaglandin and enzymes. The process of healing starts from the first treatment.

Medical use of Bionic 880

  • Wound healing (including plastic surgery)
  • Chronic Fatigue Syndrome, 96% success rate
  • Cancer and Cancer aftercare
  • Stress, Depression, Insomnia and headaches/migraines
  • Weight loss, 90% success rate (photon stimulates the body’s production of Serotonin, which suppresses the appetite
  • Treatment to give up smoking, 86% success rate (photon harmonizes production of endorphins)
  • Bacterial and viral infection – including Lyme disease, 96% success rate
  • Local pain complaints – migraines, arthritic and rheumatic pains, Sciatica, Lumbago, Herpes Zoster, skin disease (psoriasis, rosacea and eczema), severe chronic diseases, Multiple sclerosis, leaky gut, IBS and others
  • Neuralgia (pain caused by sensory nerve disorder) e.g. Trigeminal Neuralgia
  • It is a great energy booster and generator

BIONIC 880 treatment is now available in the UK (Soutwest & London)

Oxygen & Ozone Injections

Oxygen & Ozone infusions – These increase the level of oxygen in the blood to reduce inflammation, kill bacteria and improve the blood acid/alkalinity. This is available in Germany – We have yet to find a clinic to offer this in the UK.

IMG_8670
Oxygen IV Therapy
IMG_8671
Ozone Infusion Therapy

 

3d NLS Scanner

Non Linear System

A new fast digital scanning technology is available which can give a full body healthcheck in 10 minutes. Based upon German and Russian technology, the  3d-NLS Testing device compliments and validates the findings of the ampule based testing approach. The pictures produced by the scan (see below) are highly detailed and the data collected about your health far exceeds existing technology. This is a medical breakthrough that few know about in the west due to FDA protectionism of the US pharma industry, who see this technology as a threat to their symptom relief business model.  LINK

Hunter NLSFig 1. A typical NSL scan showing the Mitochondria under stress from Herpes (Mono) & Lyme disease.

 

RIFE Therapy

RIFE machine was not part of our therapy however it will be considered as a backup device to support Bioresonance.

A RIFE machine can take months and sometimes years to achieve benefits, so many people purchase their own machine and start treating themselves from home.

RIFE machines prices range from £300-£5000+ and the most advanced RIFE machines, which incorporate a plasma tube, cost between £2500-£5000. A  lower cost yet highly effective approach is to build or purchase a Doug Coil machine; the parts can be purchased for around £1-1,500. One of the lowest cost RIFE machines with a huge following is called the Spooky 2, however for Lyme disease treatment the Chinese manufacturer suggests a package including two devices and a plasma tube, which costs approx £2000.

RIFE machines typically cause a Herxeimer reaction so treatment must be given slowly to allow time for the body to detox the bio-toxins produced by the die-off of Lyme bacteria.

RIFE machines only offer therapy and have no diagnostic (test) capability. When purchased, the owner has to experiment to see if they obtain a  Herxeimer reaction or benefit from a reduction in symptoms after using the machine. The low cost Spooky 2 Rife machine offers a basic heart rate monitor biofeedback testing facility, however little has been written about how effective this testing method is.

RIFE machines cannot be used as a diagnostic device to help determine the right treatment, check treatment duration nor confirm that treatment is working. New RIFE machine owners are often at a loss to determine how to treat themselves and rely upon social media for support.

Advertisements

Medical Benefits Of Psychedelic Plants

I recently heard about a Lyme patient who was completely cured of Lyme after one treatment of Ayahuasca. On researching this it seems are others who say the same thing. Is this an option now ?

http://www.wakingtimes.com/2016/04/19/world-rediscovering-medical-benefits-psychedelic-plants/

Steven Maxwell, Contributor
Waking Times

This week Pennsylvania and Ohio announced plans to legalize medical marijuana, which will make them the 24th and 25th states to officially recognize its medicinal value. Because marijuana is successfully helping so many people cope with a host of ailments with few side effects, some other plant medicines are becoming popular for treating things like depression, drug addiction, PTSD and much more.

Where pharmaceuticals are failing, exotic plant-based psychedelics seem to be succeeding, sometimes in as little as a single dose. Over-stressed Westerners are flocking to retreats all over the world to rediscover these alternative treatments. The treatment ceremonies are typically conducted in comfortable, controlled settings by shaman trained in dosing levels.

But there are also secular biohackers, like best-selling author of The 4-Hour Workweek books Tim Ferris, who is currently micro-dosing psychedelics to test overall performance enhancement. In addition, Ferris is crowdfunding a Johns Hopkins study to clinically test using psychedelics to treat depression.

Ferris explains:

I am helping researchers in neuroscience and psychiatry at Johns Hopkins University School of Medicine to conduct a pilot study of psilocybin in the addressing of treatment-resistant depression.

A recent but still unpublished study at Johns Hopkins demonstrated rapid, substantial, and sustained (lasting up to six months) antidepressant and anxiolytic (anti-anxiety) effects of a single dose of psilocybin in psychologically-distressed patients with life-threatening cancer diagnoses. This is incredibly exciting. What if we could decrease or avoid altogether the known side-effects (and frequency of consumption) of current antidepressant drugs like SSRIs?

This study could help establish an alternative.

There have been many studies using synthesized psychedelics like Lysergic acid diethylamide (LSD). The most recent Imperial College London study showed LSD brain scans resemble a free and open mind similar to that of children.

lsd-brain-2-700x368

In the remarkable video below, a 1950’s housewife is filmed during an early LSD experiment proving it to be quite safe and pleasant.

Unfortunately, there have not been many modern studies about the potential benefits of psychedelic plants. But that seems to be changing.

Why Do Psychedelics Work?

Plant psychedelics seem to perform as a physical and spiritual detox. In fact, many of them induce vomiting and diarrhea – making them less than ideal party drugs. What’s the mechanism at work? Psychedelics appear to facilitate the rapid processing of pent-up psychological trauma. As such, when the trauma that causes anxiety, depression, PTSD or addictions is cleansed, the patient essentially feels healed.

Here are 4 Psychedelic Plants Shown to Have Healing Benefits

1. Psilocybin

magic-mushrooms

Psilocybin is a mind-altering compound similar to LSD or DMT (Dimethyltryptamine) found in over 200 species of mushrooms. Often called magic mushrooms, these edible North American psilocybin fungi have effects including “euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences,” according toWikipedia.

Clinically, magic mushrooms have helped people quit addictions according to Johns Hopkins. It is also shown to be an effective natural treatment for cluster headaches, depression and PTSD, and even shows signs of fighting cancer.

Below is a personal account of microdosing psilocybin mushrooms:

Despite swelling evidence that it has many potential medical uses, psilocybin remains illegal in the United States.  The US government lists magic mushrooms as a Schedule 1 controlled substance. However, courts have ruled that Native Americans are legally allowed to use peyotefor religious ceremonies.

2. Ayahuasca

WIKI-Ayahuasca_prep-e1336743890664

Ayahuasca is fast becoming one of the most accessible hallucinogenic plant medicines. Ayahuasca is a psychedelic brew originating from indigenous people in Amazon regions of South America. A tea is made by combining dimethyltryptamine (DMT)-containing plant species. It is typically taken orally in shaman-led ceremonies.

Participants report a deep learning about themselves and the natural habitat. Many liken it to a spiritual awakening, revelations, or a cleanse.

Don Jose Campos, author of The Shaman & Ayahuasca: Journeys to Sacred Realms, claims that “people may experience profound positive life changes subsequent to consuming ayahuasca. Vomiting can follow ayahuasca ingestion; this purging is considered by many shamans and experienced users of ayahuasca to be an essential part of the experience, as it represents the release of negative energy and emotions built up over the course of one’s life.”

The physical cleanse also serves to help expel unwanted tropical parasites, according to Wikipedia.

The psychedelic effects of ayahuasca include visual and auditory stimulation, the mixing of sensory modalities, and psychological introspection that may lead to great elation, fear, or illumination. Its purgative properties are important (known as la purga or “the purge”). The intense vomiting and occasional diarrhea it induces can clear the body of worms and other tropical parasites.

Once wild child, Lindsay Lohan, credits her sobriety and straightening out her life to a single ayahuasca experience.

Although many people have shared their incredible experiences with ayahuasca, not many clinical studies have been conducted. Yet the scientific journal Nature just announced a pilot study to test ayahuasca’s effectiveness at treating depression. Brazilian scientists also claim that ayahuasca could treat people’s cancer.

Ayahuasca is in a legal gray zone. The plants are not technically illegal but the active ingredient, DMT, is. Despite its questionable legality, ayahuasca retreats are popping up all over the world to help people detoxify their trauma.

3. Kratom

kratom-leaves

Kratom is made from the leaves of a tropical tree in the coffee family. Its common medicinal uses are pain management and mood alteration.

Philip Smith of Stop the Drug War wrote this about kratom:

Kratom is a substance that falls on the more innocuous side of the psychoactive spectrum. It is the leaves of the kratom tree, mitragyna speciosa, which is native to Thailand and Indonesia, where the leaves have been chewed or brewed into a tea and used for therapeutic and social purposes for years. According to the online repository of psychoactive knowledge, the Vaults of Erowid, kratom acts as both a mild stimulant and a mild sedative, creates feelings of empathy and euphoria, is useful for labor, and is relatively short-acting.

Of course, any psychoactive substance has its good and its bad sides, but kratom’s downside doesn’t seem very severe. Erowid lists its negatives as including a bitter taste, dizziness and nausea at higher doses, mild depression coming down, feeling hot and sweaty, and hangovers similar to alcohol. There is no mention of potential for addiction, and while fatal overdoses are theoretically possible, especially with its methanol and alkaloid extracts, in the real world, ODing on kratom doesn’t appear to be an issue. No fatal overdoses are known to have actually occurred.

Reported medicinal uses for kratom are relief for pain, anxiety and depression and it’s being studied as a withdrawal-free treatment for addiction. It’s also said to help people overcome social anxiety.

Watch a beginner’s guide to kratom below:

Although some states are attempting to ban it, anyone can currently buy kratom online.

4. Iboga

Iboga

Iboga, or Ibogaine, is the root bark of the Iboga tree found in Africa. Usually administered by shaman, Iboga induces a trance-like psychoactive state. Iboga stimulates the central nervous system when taken in small doses and induces visions in larger doses. Users report psychological introspection and spiritual exploration while in the trance.

It is gaining a reputation as a powerful alternative treatment for drug addiction and post traumatic stress disorder (PTSD). In the video below, a veteran of the Canadian Navy explains how Ibogaine helped him conquer PTSD, depression and substance abuse.

The organization for Multidisciplinary Association for Psychedelic Studies (MAPS) is currently studyingibogaine therapies in Mexico and New Zealand. Meanwhile, healing centers and retreats are popping up all over the Western world. At this time it remains illegal under the US Federal Controlled Substances Act as a Schedule 1 drug.

Best of all, millions of people take plant-based psychedelics with very few dangerous health effects, especially when compared to pharmaceutical options currently on the market to deal with anxiety and depression. However, most psychoactive plants remain illegal in the United States and around the world.

That, too, may be changing as more establishment players acknowledge the benefits.

About the Author

Steven Maxwell writes for ActivistPost.com.  

Like Waking Times on Facebook. Follow Waking Times on Twitter.

This article (The World Is Rediscovering The Medical Benefits Of Psychedelic Plants) was originally created and published by Activist Post and is re-posted here with permission. You may share or repost this story in full with attribution and source link.

~~ Help Waking Times to raise the vibration by sharing this article with friends and family…

History of Lyme & Testing

Antibody tests

Testing for the presence of B. burgdorferi antibodies used an
ELISA (enzyme-linked immunosorbent assay) that detects IgG
and IgM antibodies. The results of this test were available within
one day in 70% of cases and within three days in 88% of cases.
The total number of tests that were positive in the last three
years was 78. As the laboratory serves a number of different
hospitals and many patients were tested more than once, this case
series includes the majority of patients with a positive Lyme
antibody test.
Positive and equivocal samples on the immunoassay were sent
to the Lyme Borreliosis Diagnostic Unit of the Health Protection
Agency at Southampton, where immunoblots are performed to
assess reactivity to a range of B. burgdorferi antigens.

In this cohort, Lyme antibodies were tested for in 64 out of 65
patients with the screening ELISA; this was positive in 28 and
equivocal in eight. Immunoblots on both the ELISA positive and
equivocal samples were all positive at the reference laboratory.
ELISA was negative in 25 patients. Eleven ELISA negative blood
samples from patients thought to have the infection clinically
were sent to the reference laboratory at the specific request of
the responsible clinician, and six of these had positive
immunoblots. Overall 44 out of 64 patients had Lyme disease
serologically confirmed on immunoblot.

Source-http://lymeaware.free.fr/lyme/Diagnostiques/Lyme%20UK%20O’Connell.pdf
Chronic Lyme Post-Mortem Study Needed
Editorial by Tom Grier:
Key Words:
•Antibody: A protein produced by a white-blood-cell to attack
bacteria and viruses.
•Titer: Another word for level, as in level or amount of antibody
measured in the blood.
•Seronegative: Despite an infection there is an absence of
antibodies in the blood or serum of the patient.
•Spirochete: A spiral bacteria in the same family of bacteria as
Syphilis.
•Borrelia burgdorferi: The spirochete bacteria that causes Lyme
disease.
•Erythema Migrans: A red expanding rash on the skin caused by an
infected tick bite. An EM rash is diagnostic for Lyme disease even
in absence of a positive test.
•Antigen: Refers to a foreign substance in our blood that is
capable of causing an immune response.
There isn’t a disease in the past 100 years that has polarized the
medical community more than Lyme disease. From the very beginning,
it was misunderstood. In the early 1970’s, two concerned mothers,
Polly Murray and Judith Mensch, were convinced that the epidemic of
juvenile rheumatoid arthritis (JRA) cases they were seeing in their
neighborhoods in Old Lyme, Connecticut, were being contracted as a
result of some kind of environmental exposure rather than a genetic
disorder. After the state health department admitted that the JRA
incidence rate in that area was at least eight times the national
average, they somewhat reluctantly decided to investigate the
observations of these two woman. Murray and Mensch had to present
actual patient case histories they had collected before an
investigation was started.
In 1975, a rheumatologist named Dr. Alan Steere first described in
medical literature these abnormal cases of JRA as a new type of
arthritic disorder. He coined the term “Lyme Arthritis”. This led
to an immediate misunderstanding of Lyme disease, which was
incorrectly thought of as strictly an arthritic disease for many
years.
Six years later, in 1981, the actual cause of Lyme disease was
discovered to be a new species of spirochetal bacteria transmitted
to humans from the bite of infected deer ticks. Almost ten years
after Steere’s description of Lyme disease as an arthritic
disorder, it was now becoming recognized that Lyme disease was in
fact much more than just a new type of arthritis. Lyme disease was
now recognized as being equally capable of causing severe and
devastating neurological disorders. [Pachner AR, Steere AC. The
triad of neurologic manifestations of Lyme Disease: Meningitis,
cranial neuritis, and radiculoneuritis. Neurology 1985;35:47-53]
Dr. Willy Burgdorfer was the first to isolate the spirochetal
bacteria from the midgut of Ixodes Scapularis (deer ticks) gathered
from the Shelter Island area, located near the coast of New York
and New Jersey.
Shortly after the cause of “Lyme Arthritis” was discovered to be a
bacteria, articles appearing in medical literature quickly assumed
that the Lyme spirochete was similar to other bacterial infections.
Many treatment studies based their protocols of antibiotic
treatment on other bacterial infections, such as strep throat. The
conclusions from most early studies having short patient follow-up
concluded that you could expect Lyme disease to respond to 10-14
days of antibiotics. The antibiotics tested in the test tube and
deemed to be effective at that time included erythromycin,
tetracycline, and penicillin.
From the very beginning, treatment failures were seen in virtually
every antibiotic study done. The longer the patient follow up, the
higher the incidence of treatment failure. The medical community
blamed early treatment failures on the older antibiotics
erythromycin, tetracycline, and penicillin, and determined that
these antibiotics were not very effective at curing Lyme disease.
Ignored was the fact that the newer antibiotics were also
consistently failing to prevent relapses of active infection. Since
these early treatment studies, the concept that two weeks of
antibiotic therapy is adequate treatment for Lyme disease has
remained ingrained in the medical community’s collective
consciousness. [The Long-Term Follow-up of Lyme Disease: A
Population-Based Retrospective Cohort Study. Authors: Shadick NA;
Phillips CB; Sangha O et al. Ann Intern Med 1999 Dec
21;131(12):919-26]
*Data presented by Dr. Nancy Shadick at an International Lyme
Symposia showed that patients in the Nantucket Island study
followed for up to 5.2 years after initial antibiotic treatment had
ever-climbing relapse rates. Relapse rates in patients receiving
two weeks of IV Rocephin (ceftriaxone) could expect a relapse rate
to exceed 50% after five years.
Other factors that contribute to relapse post-treatment seem to
include length of infection before diagnosis, choice of antibiotic,
and severity of symptoms at time of evaluation.
While from the very beginning there have been thousands of patients
who have complained of still being sick and symptomatic despite
supposed adequate antibiotic treatments, most of the medical
community has ignored the patient’s observations and labeled them
as being cured – despite the fact that they still have most of the
same symptoms that brought them to their doctors in the first
place. So, what determines a cure if the patient still has the
symptoms of the disease? In many cases, it is not the patient’s
disability that determines the disease state, but rather the
presence or absence of natural immune factors or antibodies. The
problem is that antibodies are not a direct measurement of active
infection.
How could this have happened? Part of the problem was the newly
emerging science and technology of antibody serology testing known
as ELISA tests (Enzyme-Linked Immunosorbent Assay).
[ELISA tests look for an enzymatic color change that indicates the
presence or absence of Lyme antibodies in a patient’s serum. If you
still see a color change when a patient’s serum is diluted with 512
parts water, then it is said a patient has a dilution titer of
1:512. Note: Higher titer numbers do not have any correlation to
how sick a patient is feeling. In fact, a high number indicates the
presence of lots of immunity. A patient with a high titer is better
able to fight the infection than someone who is producing low
numbers of antibody or has a borderline or even negative titer.]
Not only was it clear that ELISA tests were quick and easy to
develop, but they were cheap and easy to administer. The
convenience of ELISA tests was a powerful enticement to both
doctors and patients. Let’s face it, taking a 10 cc vial of blood
is more convenient and inexpensive than having several brain, skin,
bladder, or heart biopsies costing thousands of dollars done. The
problem from the very beginning was that it was assumed and
generally accepted these tests were a better diagnostic tool than
patient evaluations based on symptoms and a response to treatment.
It was erroneously accepted that absence of antibodies in the blood
meant no infection was present anywhere in the patient’s body. Even
more disturbing was the incorrect assumption that the drop in
antibody levels during treatment indicated a microbiological cure.
Thus, many studies concluded that patients were cured if they
eventually tested negative for Lyme antibodies. Both assumptions
were and continue to be incorrect.
On paper, it certainly looks good for a doctor if he can tell a
patient that, based on the test, they are negative for Lyme
disease. However, in reality a more accurate statement would be
that the patient is simply negative for the presence of those
antibodies for which that particular test is sensitive for. Absence
of antibodies does not mean the patient cannot have active
infection.
ELISA tests can vary greatly from lab to lab. Since each lab holds
a patent on their particular test, they are all competing to say
they have the best test. It is a competitive business and certain
buzz words, such as specificity, sensitivity, efficacy, and
accuracy, are used to try to outsell one’s competitors lab tests.
This gives rise to many methods of testing efficacy implemented by
competing labs in order to say that their test is better than the
competition’s. This is usually based on predetermined laboratory
standards. Unfortunately, laboratory methods of determining an
ELISA test’s efficacy and accuracy does not directly correlate to
accuracy in determining infection in a human being.
If a laboratory tests its’ ELISA on 100 test tubes of an identical
known sample and, simultaneously, on 100 test tubes of distilled
water (the control group), and picks up 99 of the 100 samples and
only one of the control samples, they can claim their test is 99%
accurate. It had a 1% rate of false negatives and a 1% rate of
false positives. (The lab chooses what dilution titer it accepts as
positive. For one lab it maybe 1:256, while for another it may be
as high as 1:1024)
A 99% sensitivity sounds great, and most doctors and lay people
would determine that this ELISA test is 99% effective and accurate.
But these tests cannot tell you if a patient who is infected but
makes no antibodies (seronegative patients) has active Lyme
disease. Also, there is evidence that in humans with high titers,
the tests can still be as high as 55% inaccurate.
What if I told you that some manufacturer’s tests are sensitive to
only one of the antibodies we produce to the Lyme bacteria, and it
is an antibody that is rarely elevated in late Lyme? What if I told
you this test only had moderate sensitivity and requires highly
positive serum to have a reagent color change? What if I told you
that out of over 100 different Lyme ELISA tests by different labs,
each was slightly different? What would you think if I told you
that each lab holding a patent on an ELISA test presents data in
such a way to make their test appear to look better than the
competition in order to increase their profit? And, what would you
say if I told you that many medical institutions are actually
corporations that own patents on these Lyme tests, and that the
reputations of these institutions and the researchers who developed
them are all on the line if their test is found to be fallible?
What are the consequences to the reputations of these institutions
if patient who say they are still sick after treatment are denied
treatment because of these fallible tests? What if a patient
becomes disabled or dies? The admission that the Lyme bacteria is
alive and sequestered in some seronegative patients is not welcome
news to the developers of these tests. But, rather than do the type
of autopsy and tissue studies that would truly compare these tests,
the manufacturers have chosen to manufacture patient studies that
compare their tests to other equally bad serum tests. If a
carpenter has a yard stick 29 inches long and he tests its
precision with another yardstick 29 inches long, it will always
appear that his yardstick is accurate.
How do laboratory claims to the efficacy of these tests actually
stand up in the real world for the diagnosis of Lyme disease?
Hundreds of labs and ELISA tests were evaluated by independent
sources and were found several times to be less that 65% accurate.
(This was based on triple-paired identical positive serum samples
that were sent to 516 labs across the United States.) In some
cases, some labs were far below this average. Without even arguing
that some Lyme patient’s blood can be antibody negative despite an
active infection, the patient whose blood is highly positive runs
as much as a 45% chance or higher of still testing negative with an
ELISA test. So they can have loads of antibody and still test
negative simply by virtue of the lab’s inability to deliver
consistently accurate results.
Now consider this. By today’s diagnostic criteria, if you test
negative by ELISA, you don’t have Lyme disease. But, if you do test
positive, you still do not have Lyme disease until you also test
positive by Western Blot. A recent study shows that the Western
Blot can be less than 50% accurate. So, statistically, if the ELISA
test is 65% accurate and a Western Blot is 50% accurate,
multiplying these probabilities gives less than a 33% chance of
testing positive using the two tiered testing approach.
The biggest problem for Lyme patients today is that the medical
community still by and large makes the same two incorrect
assumptions about blood-based testing. This includes the more
recent PCR DNA blood tests, which have the same pitfalls as
antibody serologies in that the absence of infection of the
bloodstream does not mean absence of infection in the body. Two
important points to remember about antibody and PCR testing are: 1)
The absence of antibody (or bacterial DNA) does not prove absence
of infection and 2) the drop in antibodies (or the absence of Bb
DNA) does not guarantee that a patient is cured or that the patient
won’t relapse from active infection.
Example: Let’s consider that antibodies or bacterial DNA in the
patient’s serum are like hailstones you see during a hailstorm.
Standing in your yard with a five-gallon pail for several seconds,
you don’t collect a single hailstone. What can you conclude? The
absence of hail stones in your small bucket doesn’t exclude the
fact that it could have been hailing in your yard. You can use a
larger bucket and increase your odds, but what if the hailstorm is
just in one corner of your yard? Likewise, a small 10 cc vial of
blood may be inadequate to find an infection that isn’t even in the
blood.
A very important observation is that there is a history in medical
literature of symptomatic seronegative Lyme patients who have
received aggressive long-term antibiotic therapy and still have
been culture positive for active infection post-therapy. Tests can
be and are fallible, and infection can persist despite lengthy and
aggressive antibiotic therapy.
Other persistent infection studies have shown the presence of
Borrelia burgdorferi antigens, bacterial particles, bacterial
DNA/RNA, and the presence of the bacteria in tissue biopsies of
patients despite antibiotic therapy. Using staining techniques that
are sensitive for spirochetes, researchers have found the bacteria
in tissue biopsies from living patients as well as sequestered in
patient’s tissues at autopsy. All of these methods are a much more
direct measurement of the presence of Lyme bacteria than antibody
blood tests. But they are impractical tests for the average doctor
to perform on a daily basis.
•Why can infection be present in the body without the immune system
making measurable antibodies? Once an infection has left the
bloodstream, a patient may not make enough antibodies to test
positive. Once the infection has found a safer place in the body to
hide, it can avoid the immune system and also avoid any antibiotics
that are mainly circulating in the blood. Here is a list of
mechanisms of immune escape:
•Bb can be coated by human blocking antibody and become invisible
to killer immune cells.
•Bb can coat it self with B-cell membrane and cloak itself in human
proteins.
•Bb can find places like inside joints and tendons where it is
sequestered from the immune system and even antibiotics.
•Bb can go metabolically inactive.
•Bb can hide in the brain, heart, bladder, and possibly skin cells.
It is motile so it seeks out survivable places.
•Bb may have another form that lacks cell wall and therefore lacks
many of the antigens the human immune system would use to attack.
•Bb may hide inside some human cells.
Without infection being in constant contact with the blood-borne
immune system, the body shuts off antibody production. Antibody
levels will fall despite the fact that the infection is still
sequestered deep in the body, such as the brain, tendons, heart,
nerves, bladder, eyes, and joints. How do we know this? Patients
who have been repeatedly seronegative for antibodies have been
culture positive for the Lyme bacteria. Patients who have been
aggressively treated with antibiotics have been culture positive
for the Lyme bacteria. Despite repeated negative Lyme antibody
tests, these patients still had symptoms – symptoms that, in most
cases, responded to extended antibiotic therapies. [See references]
Because the medical community has by and large refused to accept a
patient’s symptoms as proof of infection and have continually based
their diagnosis of Lyme disease on Lyme serologies, there has been
an ever growing schism between so called “chronic Lyme patients”
and a medical community that refuses to accept their claims of
still having active infection post-treatment. In many cases, not
only are serologies used to determine the diagnosis, but the drop
in antibodies is often used to indicate a biological cure.
It has been the variable nature of the disease and its’ wide range
of symptoms, and the reliance on unreliable tests that has given
rise to two different camps concerning the diagnosis and treatment
of Lyme disease. Let’s discuss the evolution of these two opposed
paradigms of diagnosis and treatment in the next section.
The Need For A Post-Mortem Lyme Study
The medical community is unevenly divided into two opposing camps
on three major issues concerning Lyme Disease:
•What constitutes a proper diagnosis of Lyme disease?
•What constitutes proper treatment for patients with Lyme disease
who have symptoms that persist beyond four weeks of antibiotic
therapy?
•What role should Lyme tests play in both diagnosis and treatment?
The first camp on the diagnosis and treatment of Lyme disease:
The first camp, which I will call Camp A, represents the majority
of the medical community and is spearheaded by researchers from
Yale Medical, the American College of Physicians (ACP), and several
other major medical institutions. In general terms, this camp
believes that Lyme disease is best diagnosed through the use of two
consecutive serology tests; the ELISA test followed by a confirming
Western Blot. This is known as two-tiered testing. With very little
opposition from the medical community, two-tiered testing has now
become the diagnostic standard of most major medical centers.
Camp A also maintains that Lyme disease, despite the stage or
severity, is usually cured with just a few weeks of oral
antibiotics. This is by far the most popular position within the
medical community and the health insurance industry at this time.
How does Camp A make a diagnosis of Lyme Disease?
In the past, a history of a tick bite followed by a bull’s-eye skin
rash or erythema migrans rash was diagnostic of the disease, but a
diagnosis based on the rash and symptoms alone has come under
increasing attack by several advocates of two-tiered testing,
including Yale Medical [See Yale Medical Report] and the ACP.
A video training tape by the ACP is quite explicit that, in the
absence of an erythema migrans (EM) rash, the diagnosis must be
made by dual serologies and more than two weeks of antibiotics is
almost always unnecessary. In one of the video scenarios, the tape
suggests to treating physicians that patients who insist that they
have persistent symptoms post-treatment should be referred to
psychiatrists. The logic of this psychiatric referral stems from
the premise that, since antibiotics are accepted as curative, any
persistence of symptoms has to be purely psychological. So if a
patient doesn’t feel better post-treatment, send them to a shrink!
The second camp on the diagnosis and treatment of Lyme disease:
The second camp, often referred to as “Lyme advocates,” which I
will call Camp B, believes that most of the persistent symptoms
post-antibiotic treatment are caused by persistent infection. This
camp maintains that antibody serologies are poor at detecting a
spirochetal bacterial infection that has sequestered in deep
tissues and is no longer found within the bloodstream. They believe
spirochetes that have found sequestered, or privileged, sites tend
to hide in the body and are poorly detected by any means. As proof
of their position, this camp offers numerous studies which have
shown persistence of Borrelia infection post-antibiotic treatment.
Listed below are several of these published cases of persistent
infection in humans and animals post-treatment as confirmed by
either culture or tissue biopsy and stain:
•Schmidli J, Hunzicker T, Moesli P, et al, Cultivation of Bb from
joint fluid three months after treatment of facial palsy due to
Lyme Borreliosis. J Infect Dis 1988;158:905-906
•Liegner KB, Shapiro JR, Ramsey D, Halperin AJ, Hogrefe W, and Kong
L. Recurrent erythema migrans despite extended antibiotic treatment
with minocycline in a patient with persisting Borrelia burgdorferi
infection. J. American Acad Dermatol. 1993;28:312-314
•Waniek C, Prohovnik I, Kaufman MA. Rapid progressive frontal type
dementia and death with subcortical degeneration associated with
Lyme disease. A biopsy confirmed presence of Borrelia burgdorferi
post-mortem. A case report/abstract/poster presentation. LDF state
of the art conference with emphasis on neurological Lyme. April
1994, Stamford, CT*
•Lawrence C, Lipton RB, Lowy FD, and Coyle PK. Seronegative Chronic
Relapsing Neuroborreliosis. European Neurology. 1995;35(2):113-117
•Cleveland CP, Dennler PS, Durray PH. Recurrence of Lyme disease
presenting as a chest wall mass: Borrelia burgdorferi was present
despite five months of IV ceftriaxone 2g, and three months of oral
cefixime 400 mg BID. The presence of Borrelia burgdorferi confirmed
by biopsy and culture. Poster presentation LDF International
Conference on Lyme Disease research, Stamford, CT, April 1992 *
•Haupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonnherr U,
Kalden JR and Burmester GR: Persistence of Borrelia burgdorferi in
ligamentous tissue from a patient with chronic Lyme Borreliosis.
Arthritis and Rheum 1993;36:1621-1626
•Lavoie Paul E MD. Protocol from Rakel’s: Explains persistence of
infection despite “standard” courses of antibiotics. Lyme
Times-Lyme Disease Resource Center 1992;2(2): 25-27 Reprinted from
Conn’s Current Therapy 1991
•Masters EJ, Lynxwiler P, Rawlings J. Spirochetemia after
continuous high dose oral amoxicillin therapy. Infect Dis Clin
Practice 1994;3:207-208
•Pal GS, Baker JT, Wright DJM. Penicillin resistant Borrelia
encephalitis responding to cefotaxime. Lancet I (1988) 50-51
•Preac-Mursic V, Wilske B, Schierz G, et al. Repeated isolation of
spirochetes from the cerebrospinal fluid of a patient with
meningoradiculitis Bannwarth’ Syndrome. Eur J Clin Microbiol
1984;3:564-565
•Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A,
and Prokop J. Survival of Borrelia burgdorferi in antibiotically
treated patients with Lyme Borreliosis Infection 1989;17:335-339
•Georgilis K, Peacocke M, and Klempner MS. Fibroblasts protect the
Lyme Disease spirochete, Borrelia burgdorferi from ceftriaxone in
vitro. J. Infect Dis 1992;166:440-444
•Haupl TH, Krause A, Bittig M. Persistence of Borrelia burgdorferi
in chronic Lyme Disease: altered immune regulation or evasion into
immunologically privileged sites? Abstract 149 Fifth International
Conference on Lyme Borreliosis, Arlington, VA, 1992 *
•Lavoie Paul E. Failure of published antibiotic regimens in Lyme
borreliosis: Observations on prolonged oral therapy. Abstract
presented at the 1990 Lyme Borreliosis International Conference in
Sweden.*
•Fried Martin D, Durray P. Gastrointestinal Disease in Children
with Persistent Lyme Disease: Spirochetes isolated from the G.I.
tract . 1996 LDF Lyme Conference Boston, MA, Abstract*
•Neuroboreliosis: In the journal Annals of Neurology Vol. 38, No 4,
1995, there was a brief article by Dr. Andrew Pachner MD, Elizabeth
Delaney BS, and Tim O’Neill DVM, Ph.D. The conclusion of the
article was simple and concise: ” These data suggest that Lyme
neuroboreliosis represents persistent infection with B.
burgdorferi.” The study used nonhuman primates as a model for human
neuroborreliosis, and used a special PCR technique to detect the
presence of Borrelia DNA within specific structures of the brains
of five rhesus monkeys. The monkeys were injected with strain N40Br
of Borrelia burgdorferi, and later autopsied for analysis.
(For further information, please refer to the compendium of
references to the persistence or relapse of Lyme disease at
http://www.geocities.com/HotSprings/Oasi…)
Abstract summaries:
•Abstract # D654 – J. Nowakowski, et al. Culture-Confirmed
Treatment Failures of Cephalexin Therapy for Erythema Migrans. Two
of six patients biopsied had culture confirmed Borrelia burgdorferi
infections despite up to 21 days of cephalexin (500 mg TID)
antibiotic treatment. · Abstract # D655 – Nowakowski, et al,
Culture-confirmed infection and reinfection with Borrelia
burgdorferi. A patient, despite antibiotic therapy, had a recurring
Erythema Migrans rash on three separate occasions. On each occasion
it was biopsied, which revealed the active presence of Borrelia
burgdorferi on two separate occasions, indicating reinfection had
occurred.
•Abstract # D657 – J. Cimperman, F. Strle, et al, Repeated
Isolation of Borrelia burgdorferi from the cerebrospinal fluid
(CSF) of two patients treated for Lyme neuroborreliosis. Patient
One was a twenty year old woman who presented with meningitis but
was seronegative for Borrelia burgdorferi. Subsequently, six weeks
later Bb was cultured from her CSF and she was treated with IV
Rocephin 2 grams a day for 14 days. Three months later, the
symptoms returned and Bb was once again isolated from the CSF.
Patient 2 was a 51 year old female who developed an EM rash after
tick bite. Within two months she had severe neurological symptoms.
Her serology was negative. She was denied treatment until her CSF
was culture positive nine months post-tick bite. She was treated
with 2 grams of Rocephin for 14 days. Two months post-antibiotic
treatment, Bb was once again cultured from her CSF. In both of
these cases, the patients had negative antibodies but were culture
positive, suggesting that the antibody tests are not reliable
predictors of neurological Lyme Disease. Also, standard treatment
regimens are insufficient when infection of the CNS is established
and Bb can survive in the brain despite intravenous antibiotic
treatment.
•Patients with ACA shed Bb DNA post-treatment: Aberer E. et al.
Success and Failure in the treatment of acrodermatitis chronica
atrophicans skin rash. Infection 24(1):85-87 1996. ACA is a late
stage skin rash usually attributed to Borrelia afzelii, it is
sometimes mistaken for scleroderma. Forty-six patients with ACA
were treated with either 14 days of IV Rocephin or thirty days of
oral penicillin or doxycycline and followed up for one year. Of
those treated with IV, 28% had no improvement, and 40% still shed
Bb antigen in their urine. Of the oral group, 70% required
retreatment. Conclusion: Proper length of treatment for ACA has yet
to be determined.
•Logigian EL, McHugh GL, Antibiotics for Early Lyme Disease May
Prevent Full Seroconversion but not CNS Infection. 1997 ABSTRACT #
S66.006 Neuloogy Symposia, NEUROLOGY 1997; A388:48 In this study,
22 late-stage neurological patients who met the Centers for Disease
Control (CDC) criteria for Lyme disease were studied over a three
year period. Eighty-five percent of seronegative patients who still
had active disseminated infection had been treated within one month
of tick bite. This means that early antibiotic treatment may make
you test negative, but you still progress to develop encephalitis.
Without antibodies your brain has no natural immunity or local
immune system to fight the infection, so withdrawing antibiotics
causes the infection in the central nervous system (CNS) to go
unabated. Patients who go on to develop brain infections despite
antibiotics, may have suppressed antibody production thus worsening
any remaing active infection in the central nervous system.
•Valesova H, Mailer J, et al. Arthritis: A three year follow-up:
Long-term results in patients with Lyme disease followed for three
years after two weeks of IV Rocephin. Infection 24(1):98-102, 1996.
This study represents another of the problems with author’s bias
interpretation of data. Thirty-five Lyme arthritis patients were
treated with a two week course of IV Rocephin. They were then
followed for three years. At the end of the study, six patients had
complete relapses, nineteen had marked improvement, four had new
Lyme symptoms, and the rest were lost to follow up. The authors
conclusion: ” The treatment results for this group of 35 Lyme
arthritis patients are considered successful.”
Let’s look at the above figures mathematically, based on the 29
patients out of 35 who were contacted and assessed:
•19 improved = 65 %
•6 relapsed = 20 %
•4 worsened = 15 %
Does a total of 35% of patients still suffering sound like
successful treatment to you? This is a treatable disease, but you
have to treat it! What if a doctor’s child was one of the 35%? Do
you think they would continue to go untreated as suggested by the
ACP? How many patients have to relapse before treatment is
considered unsuccessful? Six patients – or 20% – had complete
relapses, yet the conclusion of the study was that, in general,
treatment was considered successful! We get better cure rates for
tuberculosis.
Animal vs. Human Studies:
Support for the theory that Borrelia burgdorferi can find safe
havens in sequestered sites despite antibiotic therapy comes from
several animal model studies. However, only a few human cases have
yet been published. This is because the tissue studies that are
required almost demand that they be done in a post-mortem exam.
(See Stanek and Appel’s work on skin biopsies verses post-mortem
exam of deep tissues in Lyme infected and antibiotic treated
beagles)
Abstract # D607 – M.J.G. Appel, The persistence of Bb in Dogs after
antibiotic treatment. Seventeen Beagle puppies were infected with
Bb from infected ticks, eleven were treated for four weeks with
either Doxycycline or amoxicillin in doses according to weight. Six
were control dogs. 1/11 had Bb isolated from skin, but 7/11 dogs
had Bb isolated from other tissues during post-mortem. All of the
persistent infected pups had persistent arthritis. Conclusion: Skin
biopsies are not predictive of persistence of infection. Also the
standard excepted four week course of antibiotic treatment in dogs
is not sufficient.
To date, no major multi-center post-mortem Lyme disease study has
ever been done on humans. Without this type of post-mortem study,
the debate between the two disagreeing camps will almost certainly
continue.
Results from the European Alzheimers study done by Dr. Judit
Miklossy suggests that post-mortem exams should not only look for
persisting spirochetes in deceased Lyme patients, but should also
look for spirochetes in the brains of deceased dementia patients as
well.
•Miklossy J, Kuntzer T, Bogousslavsky J, et al. Meningovascular
form of neuroborreliosis: Similarities between neuropathological
findings in a case of Lyme disease and those occurring in tertiary
Neurosyphilis. Acta Neuro Pathol 1990;80:568-572
•Miklossy Judit. Alzheimer’s disease a spirochetosis? Neuro Report
1993;4:841-848 Thirteen out of thirteen Alzheimer patients had
spirochetes in the brain. None of the age-matched control subjects
had evidence of spirochetes in their brains. This study suggests
that there is a correlation between an Alzheimer’s dementia and CNS
spirochetosis in Swiss patients. In other words spirochetes might
contribute to a CNS dementia similar to Alzheimer’s disease. (This
is not to suggest that all Alzheimer’s is caused by spirochetes,
but even if a small percentage of dementia can be prevented by
antibiotics then further studies are justified. None are currently
being done! ?
To do this type of tissue study of sequestered spirochetal
infections takes nearly heroic efforts in time, costs, and
diligence. Yet the few times that these types of studies have been
applied to humans have suggested that Borrelia burgdorferi can
indeed survive and thrive within the human body despite a complete
course – or even several courses – of antibiotic therapy.
Yours sincerely,
J McCullough

Link to this

Important Chronic Lyme Disease Treatment Study – A Must Read

http://www.marketwired.com/press-release/envita-publishes-important-chronic-lyme-disease-treatment-study-1977482.htm

Envita Publishes Important Chronic Lyme Disease Treatment Study

SCOTTSDALE, AZ–(Marketwired – December 16, 2014) – A revealing new study on chronic Lyme disease treatment and the inherent complexities was just published by Dr. Dino Prato and colleagues from Envita Medical Center and featured in the Open Journal Of Medical Microbiology. The study is titled, “Borrelia burgdorferi: Cell Biology and Clinical Manifestations in Latent Chronic Lyme,” and it offers an extensive overview of 157 published papers that provide crucial insight into a better understanding and the proper diagnosis/treatment of chronic Lyme disease. Starting with an in-depth explanation of the Borrelia genome and pointing to key clinical factors, it paints a picture to help physicians and patients better understand what is really occurring in Lyme disease. The paper explains the severity of the Borrelia, its complexities, and complications in the diagnostics and clinical treatment.

Envita maintains that chronic Lyme disease is very complex and the symptoms, co-infections, immunity and other complicating factors vary from case to case, and each person’s case can be unique and different. This is why personalization could be the strongest and most valuable tool moving forward in the fight against chronic Lyme disease. Armed with the correct scientific outlook and a detailed overview, we feel patients and practitioners can do better. Co-infections, patient’s immunity and genetic inborn issues of metabolism amongst other factors play a vital role in the successful treatment of chronic Lyme disease. 

According to Dr. Prato, the founder and CEO of Envita, “There are so many complex factors to chronic Lyme disease it’s so easy to see why many practitioners are not well equipped to diagnosis and treat it effectively.” Unfortunately, these oversights have led to widespread problems across the world for many patients whom are undiagnosed, or wrongly diagnosed and worse yet are unable to receive accurate treatment. It has long been known that tests have false negatives and false positives. However, good clinical judgment and experience helps to identify and recognize these unique factors present within each patient’s presentation of the disease and bring forth appropriate treatment.

The study reveals that Fibromyalgia, chronic fatigue syndrome, rheumatoid arthritis, and Parkinson’s may in fact be linked to chronic Lyme disease. This is a very important aspect of why so many Lyme disease patients have difficulty finding the right treatment. The following diagram is to better explain why certain conditions can be confused with symptoms associated with chronic Lyme disease. Of the diseases listed in this table, the symptoms of fibromyalgia are more closely related to chronic Lyme disease.

The graph below has been taken from the study published in The Open Journal of Medical Microbiology, “Borrelia burgdorferi: Cell Biology and Clinical Manifestations in Latent Chronic Lyme.”

Chronic Lyme Disease
Chronic Fatigue
Fibromyalgia
Rheumatoid Arthritis
Parkinson’s Disease

Fatigue
X
X
X
X
X

Loss of Concentration/ Short Term Memory Loss
X
X
X
X

Joint pain
X
X
X
X

Poor Sleep
X
X
X
X
X

Mood Problems/ Depression, Anxiety, etc.
X
X
X
X
X

Muscle Skeletal Pain
X
X
X
X
X

Neurological Presentation
X
X
X
X

Muscle Stiffness
X
X
X

It is important to note that many times chronic Lyme disease is treated ineffectively with antibiotics. There are several crucial, overlooked indicators within the patients’ immune system that may in fact provide a guide to whether antibiotic treatments will respond within a patient at all. Numerous other contributing issues discussed in the paper; genome of the infection, immune evasion, treatment of the disease, cellular process need to be considered in detail to establish proper medical treatment. Personalization in our opinion is likely the key to better diagnosis and treatment of chronic Lyme disease for patients.

For over a decade our experience and dedication has been focused on helping patients be free of Lyme disease. If you have any questions about Lyme disease treatment or our paper, contact us. The full version of the Borrelia study can be found here:http://www.scirp.org/Journal/PaperInformation.aspx?PaperID=51411#.VI8VEjHF8WI

Image Available:http://www.marketwire.com/library/MwGo/2014/12/16/11G028664/Images/Dino_Picture_(1)-1288048793035.jpg

Embedded Video Available: https://www.youtube.com/watch?v=4L0IrUpgN7E
Embedded Video Available: https://www.youtube.com/watch?v=jF_dnc0PUh0&list=UUfRAOQGVSwdRGEgw5UPKwOQ

IV Treatment with KDM for Lyme and can it be done on the NHS

IV Treatment with KDM for Lyme and can it be done on the NHS

via IV Treatment with KDM for Lyme and can it be done on the NHS | Phoenix Rising ME / CFS Forums.

  1. My daughter has just had the results of her blood tests back from Brussels and it looks as though she will get a diagnosis of Lyme with a few other problems, we have an appt with KDM coming up soon to discuss so I’m just trying to weigh up our options beforehand .Reading other people’s experiences it seem as though the best treatment will be IV antibiotics.

    1. How do they give these in Brussels do they put some sort of fistula in so thay can be connected up to a line each day – I’m assuming they don’t inject into a vein every day? If so has anyone had the fistula in then taken the antibiotics home to administer at home with the help of a nurse?

    2. Has anyone successfully convinced the NHS that they should give the antibiotics? Ha Ha

    Many thanks

  2. Daffodil

    DaffodilSenior Member

    Messages:
    2,920
    Likes:
    893

    hi beachy. I think KDM’s nurses do put in a PICC line in the arm and change it weekly but I do not remember exactly.

    in Canada, you can bring in 3 months worth of medicines for yourself from another country, but I am not sure about the regulations in you country, especially regarding IV medicines. you should call your health agency or border agency to find this out.

    if you had an IV nurse to administer the medicines and a local doctor to oversee the bloodwork, I don’t think KDM would have a problem letting you take the meds home…..but I cannot say for sure since the meds are IV….

  3. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    Of course you already know what a difficult road ahead you both have…
    A couple of people on here have talked about their treatment at KdMs, with IVs seems they have 4 days on and 3 off weekly.. The canula??is left in for the 4 days, new one each week. The course is 12 weeks IVs, 3 different ones. Is he planning on treating co-infections first?
    if you wanted to get a nursing agency here to do the IVs, need to get their agreement first, you would need to get the abx from the clinic I would think though.
    Quite a few people have been to the clinic from PR but not heard of anyone having the IVs at home in the UK. maybe Lyme Disease UK facebook forum may have members who have.

    My problems with going to the clinic were,, lack of suitable accommodation close to the clinic, availability of fresh groceries for my limited diet. I can’t walk far so public transport is a no no. Cost of taxis are astronomical.

    Last edited: Oct 30, 2014
    justy and merylg like this.
  4. brenda

    brendaSenior Member

    Messages:
    1,323
    Likes:
    663
    UK

    If you have a positive test for Lyme you could try Breakspear where they do port administration on the NHS but you need to be funded.

    justy likes this.
  5. Sushi

    SushiModerator and Senior Member Albuquerque

    Messages:
    7,230
    Likes:
    6,260
    Albuquerque

    Here is a long thread by a member who had the IVs at home through a home health agency–but not in the UK. It does explain how it works though. There are also quite a few members who have written about getting the IVs at Himmunitas in Belgium.

    Best wishes!
    Sushi

    Hanna, justy, merylg and 1 other person like this.
  6. justy

    justySenior Member

    Messages:
    2,723
    Likes:
    3,030
    U.K

    Hi Beachy, I am a patient of KDM also.
    It is very unlikely that you will get any NHS help based on KDM’s findings. If you can convince her GP to do the NHS tests for Lyme and they come up positive then you may get a few weeks oral antibiotics to deal with it. I odnt know of anyone who has managed to get more help than this. I looked at iv’s at home with nursing agence and couldn’t find anyone to do it.

    As I am so severely ill I also didn’t want to risk doing this far away from a knowledgeable Dr… I am planning on going to Brussels for IVs early next year and have found a couple of places to stay, but also open to sharing with other patients.

    Valentijn and Hanna like this.
  7. beachy

    beachy

    Messages:
    7
    Likes:
    5

    Thanks everyone for the suggestions. We have talked to KDM now and he wants to treat the mycoplasma infection first. I thought he would have decided the treatment plan before our conversation so that we could have had a more useful discussion, but unfortunately he hadn’t so I still don’t know very much more.

    he did agree though that my sister-in-law who is a nurse would be able to administer any intravenous anti-biotics so that was good news. we would just need to get a PIC line put in which we could get done in Brussels or hopefully one of the local private hospitals would be able to do it for us.

    We haven’t talked to the GP yet but she had already had a negative Lyme test in the UK so probably won’t be any use.

  8. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    The quote I got for a PICC line from a private hospital in Hertfordshire was £3000, hope you can get a better rate elsewhere.

    justy likes this.
  9. Jonathan Edwards

    Jonathan EdwardsBoard Member

    Messages:
    1,102
    Likes:
    5,071

    I am just wondering if your daughter is a minor and whether your sister-in-law would be legally indemnified for treating her? Nobody tends to think about these things in advance but very occasionally things go badly wrong.

    justy likes this.
  10. Min

    MinSenior Member

    Messages:
    1,284
    Likes:
    1,533
    UK

    The NHS test for Lyme is notorious for giving false negatives, it is not fit for purpose.

    if you test positive privately, as I did, the NHS will not accept it and you will be denied treatment. The very few Lyme literate Lyme doctors in the UK are hounded by the GMC. Accessing treatment unless you can afford the Breakspear seems impossible.

  11. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    @Jonathan Edwards
    Prof KdM will prescribe the IV abx, as long as they are administered by a qualified nurse I wouldn’t have thought there would be a problem with having them done in the UK. FWIW I would get things set up at home but then probably arrange to stay at the clinic for the first 4 days of each abx just to make sure the doctors are on hand for any reactions (hopefully not). You would than have 3 days to get home and continue abx for the next 3 weeks.

    Hanna and Valentijn like this.
  12. ukxmrv

    ukxmrvSenior Member

    Messages:
    3,517
    Likes:
    2,055
    London

    If you do need a nurse from an outside agency I used the company Healthcare@home for IVIG infusions at home. They might be able to help with the AB’s if your SIL isn’t able to.

    https://www.hah.co.uk/

    Valentijn likes this.
  13. Jonathan Edwards

    Jonathan EdwardsBoard Member

    Messages:
    1,102
    Likes:
    5,071

    People forget about indemnity and it is not a trivial issue. I encountered it when setting up my research on rituximab. At that time I had blanket cover for anything I did on NHS premises under what used to be called Crown Indemnity. Then everything changed and a year or two later I would have had to make specific arrangements for indemnity for my research even though I was doing it in an NHS/University department.

    A nurse administering a drug as part of her employment, whether NHS or private, will have in place indemnity for whatever she does either through the NHS scheme or a personal insurance arrangement. Doctors have a hybrid system with both so they pay insurance premiums to a non-NHS organisation as well. However, if a nurse gives a treatment which is not part of her employment duties she will need to make sure she is indemnified for what might happen. Since this is not a routine situation I strongly suspect that this would not be at all easy – maybe even impossible in practice. No insurance company is going to provide cover for giving a treatment to a relative as a favour.

    I don’t want to alarm people but what if a catheter is dislodged or gets infected and there is an embolic stroke or endocarditis that leaves the patient disabled life – long, with a reasonable claim for millions of pounds of care costs? I would not want to put a sister-in-law in the situation of being on the receiving end of such a problem. I administered IV chemotherapy to my wife forty years ago because it was more convenient for me to do it than for her to go to an NHS hospital once a week. But if anything had gone wrong I don’t thhink we would have ever had a case for compensation. I am not sure I would do it now. I might, but I am not sure. And if the patient here is a minor the issues are much greater.

    SOC and NK17 like this.
  14. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    Ah but therein lies the difference. Your perspective is based on the risk of having to pay compensation if something goes wrong. Of course I understand that, the NHS is a massive target for claims, some justified, others not so???

    We are coming at life (the one we don’t really have) from a different perspective.
    When you are so sick, all you can do is cover bases as much as possible and then go for it and hope for the best. We have no choice other than to stay sick for the rest of our lives. We have to help ourselves, at least some doctors like KdM are trying to help us, nobody in the NHS is listening.
    The relative in question is aware of all the medical risks, she will face them daily in NHS practice. People like her are an absolute blessing.
    Also what is there in life that doesn’t have a risk?

    Valentijn likes this.
  15. Jonathan Edwards

    Jonathan EdwardsBoard Member

    Messages:
    1,102
    Likes:
    5,071

    Maryb, I think you are missing my point. I have nothing to do with the NHS now and was not employed by the NHS. I am not talking about costs for the NHS. I am simply saying that one has to consider whether one is prepared to make one’s sister-in-law bankrupt, not to mention the effect of guilt on the rest of her life? The answer may be yes, the calculated risk is reasonable to take, but I think people need to be sure they understand the implications. I have seen guilt destroy families in this sort of context.

    NK17 and Hanna like this.
  16. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    @Jonathan Edwards
    No but this is how NHS personnel think is it not. Why would the SIL be made bankrupt? I would trust my family with my life. Do you mean the NHS would sue the SIL if they had to pick up the care of anyone left disabled?

  17. Jonathan Edwards

    Jonathan EdwardsBoard Member

    Messages:
    1,102
    Likes:
    5,071

    I cannot see that what NHS people think has anything to do with this problem Maryb. Of course the NHS would not sue. But the sister in law might lose her job. I think you need to think through what might really happen here. Think hard. Human nature is complex and unpredictable, especially in the face of illness, as you know. I have already said enough to upset the people involved more than I would like, but I think these things do have to be said.

    NK17 likes this.
  18. Little Bluestem

    Little BluestemSenescent on the Illinois prairie, USA

    Messages:
    2,681
    Likes:
    2,016
    Midwest, USA

    @maryb, I think what Jonathan Edwards is saying is that if the family hires a home-health nurse to do the IVs and something goes horribly wrong, the insurance of the home health company would pay for the care of the child. If the SIL does it outside of her work and something goes horribly wrong, the parents would have to stand all of the expense of caring for the child themselves or sue the SIL.

    SOC and ukxmrv like this.
  19. maryb

    marybiherb code TAK122

    Messages:
    2,917
    Likes:
    2,052
    UK

    @Little Bluestem
    I understand that but what I say is, we either accept the risks or not, its a big decision I agree. In the end the parent will make the right choice for their child, that’s what they do. I’ve met so many heartbroken parents over the past few years, their despair is so evident. I just wish them all the best luck in the world and that their children will grow up to live normal lives, that’s all they want.
    I consider myself as ‘lucky’, I had a good life, professional career, children,g/children, happy social/hobbies. before this illness got me. I’m not posting again on this thread as I’ve said what I think.

    Valentijn likes this.
  20. beachy

    beachy

    Messages:
    7
    Likes:
    5

    As my daughter is an adult she will be making her own treatment choices, I’m just trying to help her find out what her options are. We had already thought about the implications of IV treatment at home, but actually there are also serious considerations for having it done in Brussels, not least being the fact that if anything goes wrong normal travel insurance won’t cover you for health related travel . We have at least 2 months now to think about it as she needs to first start a course of oral anti-biotics

Alternative Treatment – Hyperbaric Oxygen, Bee Venom treatment & Antifungal medications

Alternative therapies[link]

A number of other alternative therapies have been suggested, though clinical trials have not been conducted, so the therapies are not known to be scientifically sound. For example, the use of hyperbaric oxygen therapy has been discussed by CAM enthusiasts as an adjunct to antibiotics for Lyme.[126] Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro and in vivo.[127] Anecdotal clinical research has suggested antifungal azole medications, such as fluconazole, could be used in the treatment of Lyme, but the use of these drugs has yet to be tested in a controlled study.[128]

Alternative medicine approaches include bee venom, because it contains the peptide melittin, which has been shown to exert inhibitory effects on Lyme bacteria in vitro;[129] however, no clinical trials of this treatment have been carried out.

 

Portable Far Infrared, FIR Sauna

It’s design include the most desirable features the expansive and fancy Saunas have. With this Portable Far Infrared, FIR Sauna you will have even more conveniences and benefits then with a large Sauna. This Far Infrared, FIR sauna heater box applies hi-tech of super conductive and ultra thin carbon fiber heating element. The high heat efficiency helps perspire, activate the build, promote blood circulation, and keep body healthy. 10 minutes of sauna bath corresponds to 30 minutes of jogging for exhaust sweat. With its satisfying design, your head and hands can extend out for reading, watching TV, or listening to music. The advantage of the Far Infrared, FIR sauna over a conventional sauna Far infrared portable sauna unit includes Far infrared sauna box New Features Add-On with Negative Ion Far infrared carbon fiber heating panels Intelligent temperature automatic preset control for various level of heating Master controller unit Handheld timer and heating level controller Compact folding chair Heating Foot pad Foam floor pad Compact Folding Chair Handheld Control for control of time and heating level Master Controller Unit Foam Floor Cushion Zipper for Neck and Both Arms Zipper for Entrance Regular Size: 27in wide x 32in deep x 38in high Large Size: 32in wide x 34in deep x 41in high AC 120v 60hz Power Supply Fir Material Energy Emission . . . . 97% Automatic Preset Timer Control . . . . 5, 10, 15, 20, 25, 30 min. Low Operating Cost . . . . approximately $for 30 minutes use

http://www.amazon.com/Infrared-Portable-Sauna-Negative-Detox/dp/B000ZGQUJO/ref=pd_sbs_sg_1/181-9277157-1809929?ie=UTF8&refRID=17BA3JJ3KZ1H8RJDF7CR

Lumbrokinase treatment for Lyme

New Hope for Most Severe Chronic Cases of Lyme Disease! Part One

New Hope for Most Severe Chronic Cases of Lyme Disease! Part One

Has anyone heard of Lumbrokinase?  Well, if you haven’t, lumbrokinase is a group of six, novel proteolytic enzymes derived from the earthworm Lumbricus Rubellus, and it is slowly establishing itself as possibly the best and brightest new treatment for chronic Lyme sufferer.

To purchase http://www.pureformulas.com/lumbrokinase-60-capsules-by-allergy-research-group.html#sthash.cCFZIyz0.dpbs

I say “new treatment” because it is new information for me – generously supplied by a fellow “Lymie” Ted Patterson who has tried it and “feels better than he has in years”.  The more I researched this enzyme, the more excited I have become.

First, lumbrokinase has been used successfully in China’s four top hospitals in nerve and infectious diseases since 1995 without any harmful side effects.  Initially used for the potent ability to dissolve blood clots and vein thrombosis, it was soon discovered to improve the quality of blood in a number of ways that are still being discovered.

According to Allery Research Group,  medical reports from leading researchers and doctors have further discovered the power of lumbrokinase to not only dissolve clots which obviously helps protect against heart disease and strokes, but also:

to lower fibrinogen levelsin cancer patients, which is strongly associated in scientific studies with better outcomes,

  • strongly associated in scientific studies with better outcomes, less metastasis, and slower growth of tumors;
  • to offer antiplatelet, anti-thrombotic and self-destructive cellular activity, remarkably regulating hypercoagulation; and most importantly for us,
  • to dissolve bacterial biofilms present in chronic infections in conditions like autism and Lyme disease, allowing antimicrobials and anti-bacterials as well as our own immune system to work effectively and quickly to destroy the colonies that hide behind the biofilms.

Biofilms have been recently discovered as one of the key biological roadblocks to curing many chronic diseases, especially (for our purposes) Lyme disease. It is a remarkable breakthrough, and it ultimately could have a huge effect on Lyme disease sufferers and possibly their life insurance quotes and policies because of a longer life expectancy among those infected.

Peta Cohen, M.S., R.D.,  is the founder of Total Life Center in Northern New Jersey, and has a Masters Degree in Clinical Nutrition, was recently interviewed by Allergy Research Group (read entire interview here), and offers these insights into biofilms:

“I do a tremendous amount of testing and assessing the children through urine and fecal analysis. What got me so interested in nattokinase and lumbrokinase was the concept of what a biofilm infection actually is. If you do a medline search on biofilms and platelet aggregation, fibrinogen, and fibrin, boom, it’s there right in your face.

“Bacteria build biofilms by first aggregating together, and then rapidly weaving this protective web or matrix around them.  They build a polymeric matrix. It’s a sticky, gluey, mucus-y goop and it’s got fibrin in it to give it an intact structure. The bacteria recruit fibrinogen to create fibrin as part of that matrix. At that point they can shed their outer membrane, which has the proteins that serve as antigens and as a target of the missile of the immune system. They’re very protected. They’re very crafty in creating a way to survive and procreate and hide from the immune system.”

In neurological Lyme disease, the biofilm is believed to be constructed of actual bits and pieces of our myelin sheath which covers and protects our actual nerves that make up our central nervous system.  So when the immune system calls for killer cells to destroy the invaders, our immune system can actually attack our central nervous system trying to break through the biofilm and destroy the infection which they cannot do.

So, as lumbrokinase dissolves this biofilm, we have hope that our killer cells, or in more critical cases where the immune system is no longer working effectively, antibiotics (pharmaceutical or herbal) will be able to destroy the infection and return us to health!

See product here.

Look for Part Two on “nattokinase”, and please comment if you have any experience to relate regarding lumbrokinase.

To read excerpts from LLD’s who are using lumbrokinase successfully, read:

Two Doctors Use Lumbrokinase to Help Conquer Lyme Disease

– See more at: http://lymediseaseresource.com/wordpress/new-hope-for-most-severe-chronic-cases-of-lyme-disease-part-one/#sthash.0wOhm6d3.dpuf

Hyperbaric Oxygen treatment for Lyme

http://www.subwayscuba.com/recompression_chambers_malta.html

The hyperbaric unit in Gozo started being used again on May 1 after a stoppage of six months, the Health Ministry said yesterday.

Health Minister Godfrey Farrugia visited the unit yesterday. Since its reopening, the hyperbaric unit has treated four emergency call outs for divers and 40 oxygen therapy sessions.

The Ministry for Health was planning to train another two doctors in hyperbaric medicine at the hospital, Dr Farrugia said.

 

http://hboxygen.freeyellow.com/id36.html

http://wn.com/lyme_disease_and_hyperbarics

 

Hy­per­bar­ic oxy­gen Ther­a­py for Lymes dis­ease part-1
http://www.balancedhealthtoday.com Hy­per­bar­ic ther­a­py does not res­ur­rect dead brain tis­sue…
pub­lished: 17 Jan 2009
5:39

Hy­per­bar­ic Oxy­gen ther­a­py for Lymes dis­ease
http://www.balancedhealthtoday.com Hy­per­bar­ic ther­a­py does not res­ur­rect dead brain tis­sue…
pub­lished: 17 Jan 2009
4:21

Hy­per­bar­ic oxy­gen re­vers­es pa­tient’s Lyme mis­di­ag­no­sis
http://www.hboinfo.com Julie de­scribes the tor­ment of mis­di­ag­no­sis and in­ap­pro­pri­ate phar­ma­ceu­tic…
pub­lished: 16 Apr 2011
au­thor: Robert Sands
8:21

Lyme ban­ished using hy­per­bar­ic oxy­gen FOX TV
http://www.hboinfo.com Fox 6 News re­ports on Heal­ing Cham­bers In­ter­na­tion­al’s cham­bers. Pa­tient c…
pub­lished: 07 Jan 2012
au­thor: Robert Sands
LYME DISEASEPATHOLOGY: The Borrelia burgdorferi (Bb) spirochetes, which are the cause of Lyme disease, are commonly transmitted by deer tick bites. They are anaerobic or microaerophilic (intolerant of oxygen or elevated levels of oxygen).  The Bb spirochetes burrow deeply into muscle and nervous tissue and cause a variety of symptoms. Primary symptoms are aninfection localized to the site of the bite, which may be seen as a red, progressively expanding circular lesion, and which may be accompanied by flu-like symptoms. Secondary symptoms include joint and muscle pain, sore throat, fever, chills, headaches, weakness, intolerance to light, secondary skin rashes, difficulty in mentation (thinking), muscle and nervous tissue fatigue, and heart palpitations. Advanced symptoms include arthritis, irregular heartbeat, severe headaches, loss of sensation, carditis, meningitis, cranial neuritis, radiculoneuropathy, and migratory pain in joints, tendons, bursae, muscles or bones. In stage 3, the spirochetes may cause arthritis of large joints, especially in the knees, encephalopathy, and advanced atrophy of the skin of the upper or lower limbs known as Acrodermatitis Chronica Atrophicans (ACA). In the end stage of ACA, the skin becomes so atrophic that the superficial veins and subcutaneous tissue become prominent and are easily lifted and pushed into folds.  If left untreated or not treated promptly, Lyme disease symptoms may become chronic; the disease may cause permanent disability and, rarely, death.  Lyme disease is often misdiagnosed as another type of illness based on the presentation of symptoms.

 

The Bb organism is capable of encapsulating itself in the body’s protein, and thus the immune system fails to react to the Bb organism as a foreign organism that should be destroyed.  The spirochetes typically burrow deeply into the fatty muscle and nervous tissue where they are not detected by immune system antibodies.  Hidden in a cloak of protein and in areas of low oxygen concentration (low pO2 levels), they release neurotoxins which circulate through the body’s fat storage systems triggering classic Lyme symptoms.1  Spirochetes can hide withinthe body’s cells and may enter a dormant state that will not be affected by antibiotics. Chronic Lyme has increased distribution of spirochetes in non-perfused tissues.

 

When the disease is discovered during the first six months of infection and is treated in its early stages, the patient generally responds well to oral antibiotics and the spirochetes are killed.  However, spirochetes replicate slowly and have the capacity to lie dormant for as long as 10 months. The only time the spirochete is vulnerable to antibiotics is during a growth/reproduction stage.  Further complicating matters, some enzymes produced by the spirochetes confer resistance to some kinds of antibiotics, making treatment of this disease, once a person has been infected for longer than six months, challenging.2

 

TREATMENTS

 

ANTIBIOTIC THERAPIES

 

ORAL ROUTE

 

Penicillins and Cephalosporins

 

This antibiotic therapy is the first line defense in the treatment of Lyme disease. It circulates mainly in the body’s fluids but has difficulty penetrating into muscle tissues to eradicate Bb bacteria and is incapable of entering cells where Bb organisms can reside. If treated with the penicillins or the cephalosporins in the primary stage, the person usually responds well.  If the symptoms have entered stage II or later, where the Bb spirochete has entered muscle tissue, a second form of antibiotic therapy is often necessary and may be used in combination with the primary therapy.

 

Macrolides (azithromycin)

 

This antibiotic family can attack Bb organisms that may be established in the body’s cells as well as killing Lyme bacteria residing outside the cells in deep tissue areas of the body. Macrolides may not be able to penetrate the full depth of muscle tissue. Macrolide antibiotics are not recommended as first-line therapy for early Lyme disease (E-I). When used, they should be reserved for patients who are intolerant of amoxicillin, doxycycline, and cefuroxime axetil.3

 

If the person does not respond well to oral antibiotics, IV therapy may be used and may involve different antibiotics.  Oral therapy is easier to administer than IV antibiotics and is considerably less expensive. It also is associated with fewer serious complications. Its disadvantage is that some patients treated with oral agents have subsequently manifested nervous system involvement, which may require IV therapy for successful treatment.

 

IV THERAPY

 

Ceftriaxone (Rocephin) and Vancomycins

 

IV therapy is useful in that it provides antibiotics “ready to use,” that do not have to be absorbed through the digestive system as with oral antibiotics.  IV drugs are often prescribed because of the failure or intolerance of oral therapy and may be other classes of antibiotics. Rocephin is still the most used IV antibiotic, often delivered via a peripheral IV line and may well be given with a macrolide to increase the overall effectiveness.  There are several IV antibiotics that may affect the Bb organism, such as doxycycline and vancomycin.

 

Long term antibiotic use can be problematical to a person’s overall health and the spirochetes may become drug resistant.  Persons who don’t respond well to conventional drug therapy or who have drug sensitivities or allergies, or become sensitive or allergic, may respond well with complementary therapies. 

 

ALTERNATE AND COMPLEMENTARY THERAPIES

 

These therapies have been shown to have a positive influence to some degree on symptoms for persons with Lyme disease2

 

      Vitamins

      Diet

      Exercise

      Immune modulation

      Reishi spore extract, transfer factor

      Acupuncture

      Hyperbaric Oxygenation

 

In pursuing hyperbaric oxygen (HBO) therapy to treat Lyme disease, it has been shown in studies by both Charles Pavia, PhD, and William P. Fife, PhD, that spirochetes exposed to an increased partial pressure of oxygen could not survive. Bb organisms do not thrive in elevated pO2 levels above 70-80 torr. Hyperbaric oxygen therapy involves delivering 100% oxygen to a patient at a greater-than-sea-level atmospheric pressure. Normal pO2 levels of tissues increases from a typical 35-40 torr to 999+ torr when measured by transcutaneous oximetry at 2-3 ATA (atmospheres absolute). Arterial saturation of oxygen rises to about 22 mL/dL, of which nearly 25 percent is dissolved in the plasma4.  The cerebral-spinal fluid is also supersaturated with molecular oxygen.  Life could be sustained without hemoglobin at this level.

 

Because plasma seeps into areas between cells, this increase in the amount of oxygen carried by the plasma allows oxygen to be distributed at very high levels deep within muscle and body tissues, and to areas where normal blood flow is compromised. This causes accessible Borrelia burgdorferi spirochetes to be destroyed, interrupts the reproductive cycle or forces them into spore (inactive) form. 

 

In addition to the increased pO2 level, hyperbaric oxygen therapy also stimulates the immune system response which increases the production of phagocytes, the white blood cells that ingest and destroy foreign matter, and the production of leucocytes, the white blood cells that defend the body against infective organisms.  It is bacteriostatic—it interferes with the ability of the organism to reproduce, and is bactericidal and directly attacks the cell wall of the bacterium, causing it to rupture, then die.

 

Hyperbaric oxygen therapy produces natural free-radicals that are believed to have an antibiotic-like effect.5 The Bb organisms can be killed by oxygen free-radicals. 

 

Over a series of treatments, HBO therapy causes angiogenesis, the formation of new capillaries.  This is important for the distribution of the Penicillin and Cephalosporin families of antibiotics which travel via blood flow.  The new blood vessels allow the antibiotics to reach tissue that was poorly perfused, and the combination of HBO therapy and antibiotics is greater than the effect of either one alone.  Antibiotics may be more readily incorporated into the cell wall of the bacteria in the presence of elevated oxygen tension. 

JARISCH-HERXHEIMER RESPONSE

 

 

The Jarisch-Herxheimer response (Herxheimer) occurs when symptoms recur, flare up or become exaggerated and is an increase in the severity of symptoms a person suffers.  It is an indication of the death of spirochetes.  Dead and dying spirochetes release endotoxins as their cell walls break down.  These endotoxins exacerbate symptoms and can be fat soluble which slows elimination from the body, extending the symptoms.  In the normal 28 to 32 day life-cycle of a spirochete, as adult bacteria reproduce and die, a person experiences a Herxheimer usually during this same period. Outside of this normal reproductive die-off, a Herxheimer is used as a clinical diagnostic tool to confirm the effectiveness of antibiotics and other treatments such as HBO therapy.

 

Under hyperbaric oxygen therapy, a Herxheimer response usually occurs within days to weeks of starting therapy.  Improvements from hyperbaric oxygenation may not be observed until 3 weeks to 3 months post therapy due to the effect of endotoxins trapped in fat soluble tissues. 

 

Hyperbaric oxygen is tolerated by most patients and is a complement to traditional antibiotic therapy.  It also provides relief for those patients who cannot tolerate antibiotics or who have become stagnant in their antibiotic response. 

 

TREATMENT PROTOCOL

 

The hyperbaric oxygen treatment protocol for Lyme disease is 1.8 to 2.4 atmospheres absolute (ATA) for an initial series of 40 treatments. This time frame covers the typical reproductive cycle of the Bb organism.  A repeat series is recommended after 6-8 weeks if symptoms recur and single or dual treatments may help to stem the spirochete reproductive cycle before a second full series is deemed necessary.  If tolerated, antibiotic therapy is recommended to be continued as this will help to eliminate remaining bacteria. 

1.  http://www.chronicneurotoxins.com/learnmore/lymedisease

2. Burruscano, Joseph J., Jr., M.D. Managing Lyme Disease

3.  Practice Guidelines for the Treatment of Lyme Disease; Gary P. Wormser et al. 

     CID 2000;31

4.  Hyperbaric Oxygen Therapy Gains Respect in Medical Circles, Deborah S.

     Cowder, As, RRT. Issue Date:  7/29/2002

5.  An Overview of Lyme Disease and Hyperbaric Oxygen Therapy; Mitchell L.

     Hoggard and L. James Johnson

Copyright © 2008 The Robert M. Lombard Hyperbaric Oxygenation Medical Center, Inc. All Rights Reserved

Low secretary iga

July 14, 2013 by Dr. David Jockers
Filed under Natural Healing

Leave a comment

Sun. July 14, 2013 by Dr. David Jockers
(NaturalHealth365) Are you interested in naturally eliminating digestive problems? If so, then let’s look at ways to boost your immune system by balancing secretory IgA – which protects you from infections.

Every mucosal membrane surface such as the eyes, nose, throat and intestinal system represent a large portal of entry for pathogenic bacteria, viruses and yeasts. The body’s immune system utilizes a combination attack through innate mechanisms and acquired adaptations.

The innate immune response includes mucus formation, lactoferrin, lysozymes and cytokinetic inflammatory activity. The acquired system produces anti-bodies with the primary mucosal antibody being secretory IgA.

This antibody response is one of the most critical component to protecting the body against parasitic dominance.

Secretory IgA is the secreted form of an antibody in the blood called IgA. IgA is produced in the blood, taken into the gut, secreted across the mucosal lining into that mucous layer that is the surface lining of our digestive tract. It is the mucosal immune barrier or first line immune defense.

SIgA lies within the mucosal membrane of the entire digestive tract as well as our lungs, sinuses, eyes, urethra and vagina. It plays a significant role in neutralizing various pathogens like viruses, Candida, bacteria, protozoa and hemoliths.

The health problems associated with low SIgA levels

When SIgA is elevated it indicates an acute immune reaction within the gut. This could indicate an acute bacterial or parasitic infection. When s IgA is low it indicates an overall deficiency of this immune chemical. When this is low on a stool test the individual will also express food allergens, have elevated Candida yeast and have dysbiosis or abnormal bacterial balance in their gut.

Individuals with chronic gut problems, IBS, Candida, Crohn’s disease, ulcerative colitis and autism typically have low SIgA. This is a sign of chronic stress in the body that has drained the immune system and the adrenals. Chronic infections, environmental toxins, poor lifestyle could all be the major causes behind this.

How to naturally balance your SIgA levels

The first step to increase (or decrease) SIgA naturally is to use an anti-inflammatory diet. The most common food allergens include all grains, pasteurized dairy, soy products, eggs, nuts and high-sugar fruits. Utilizing intermittent fasting strategies and going 18-20 hours of fasting with only clean water, herbal teas, organic broths and light fermented beverages each day is highly recommended.

An advanced bone broth fast with organic, grass-fed beef bones and loads of garlic and onions can be extremely effective at helping the gut to reseal and boost SIgA levels. This should be a 10-14 day fast if the levels are severely low and 3-7 day if they are more moderate.

It is important to provide the gut and the immune system with the key nutrients they need such as vitamin C, zinc, selenium, glutamine, choline, glycine, glutathione and essential fatty acids among other things. A whole food based multi-vitamin without any filling agents such as magnesium stearate is very helpful.

Using non-denatured whey protein from grass-fed cows will boost glutamine and glutathione levels and is easily absorbed into the body. It is highly recommended if the individual can tolerate it. If they have allergenic reactions to whey than use a hypoallergenic protein powder made up of sprouted hemp and pea protein.

Great ways to naturally raise your SIgA levels

There are a few things that boost Secretory IgA levels naturally. Colostrum is an immunoglobulin blast that is secreted from mom’s breast in the early stages of breast feeding. Colostrum is loaded with antibodies that stimulate SIgA levels. Fermented dairy from 100% grass-fed cows is loaded with acidophilus, bacillus and saccharomyces boulardii species of probiotics that all help to stimulate S IgA levels.

Beta Glucans are polysaccharide fibers that are considered biological response modifiers because of their ability to activate the immune system. They help boost the production of SIgA. These are found in the highest concentration in different types of mushrooms such as reishi, shiitake and maitake. Cayenne pepper also has the ability to stimulate B-lymphocytes into manufacturing more SIgA.

How can I naturally lower SIgA?

Elevated SIgA is a sign of an acute infection and the immune system is running on high. Using an anti-inflammatory diet that includes the bone broth fast described above is especially helpful. One can also take systemic enzymes and high dose probiotics to help modulate the immune system. Essential fats from a high quality fish oil and grass-fed meat products are extremely critical as well.

Fermented vegetables load the body up with enzymes, probiotics, organic acids and highly bioavailable nutrients that raise SIgA levels. Other herbs such as turmeric, basil, oregano, garlic and thyme are especially helpful. Fermented herbal botanicals, apple cider vinegar, coconut kefir and kombucha should be used as well.

How long does it take to boost SIgA?

Secretory IgA is generally an indication of the immune system in the gut which is our first line immune defense and it is called the mucosal barrier. When the gut is damaged and leaky it causes chronic stress and poor healing. The faster the chronic stressors are removed the faster the individual will get well. The average period is a good four to six month process for complete healing to take place.

In some cases, it may even take years to finally get SIgA levels up to normal.

The variable in all accounts is the individuals’ unique healing process. Many individuals have a severe leaky gut and are loaded with Candida, viral infections, worms and other parasites and also have heavy metals and industrial toxins as well as physical stressors such as poor posture and breathing habits. These individuals are challenging because they must correct each of these imbalances. The longer each of these challenges persists it will contribute to the formation of other stressors and keep the adrenals weak and tired.

The faster we can get the gut healed and restored and use a ketogenic style, anti-inflammatory diet that is loaded with fermented foods the faster the body will be able to detoxify and restore healthy function to the gut, liver and adrenals.

Please note: Intermittent water fasting is one of the best strategies for boosting our healing potential.

Looking for natural health solutions? Sign up now – for our free, weekly show featuring the greatest minds in natural health and science plus a free gift!

About the author: Dr. David Jockers owns and operates Exodus Health Center in Kennesaw, Ga. He is a Maximized Living doctor. His expertise is in weight loss, customized nutrition & exercise, & structural corrective chiropractic care. For more information – visit: DrJockers.com. Dr. Jockers is also available for long distance phone consultations to help you beat disease and reach your health goals.

References:
https://www.metametrix.com/files/learning-center/articles/Secretory-IgA.pdf
http://www.yeastinfection.org/how-to-increase-your-siga-levels/
http://en.wikipedia.org/wiki/Immunoglobulin_A

– See more at: http://www.naturalhealth365.com/natural_healing/digestive_problems.html#sthash.wDklJfy2.dpuf

Benefit of intravenous antibiotic treatment of neurologic Lyme disease

Int J Gen Med. 2011; 4: 639–646.
Published online 2011 September 6. doi:  10.2147/IJGM.S23829
PMCID: PMC3177589

Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease

This article has been cited by other articles in PMC.

Abstract

Background

We have shown previously that extended intravenous antibiotic therapy is associated with low morbidity and no mortality in patients referred for treatment of neurologic Lyme disease. In this study, we evaluated the benefit of extended intravenous antibiotic therapy in patients with symptoms of neurologic Lyme disease.

Methods

Patients with significant neurologic symptoms and positive testing for Borrelia burgdorferi were treated with intravenous antibiotics, and biweekly evaluation of symptom severity was performed using a six-level ordinal scale. Four symptoms were selected a priori as primary outcome measures in the study, ie, fatigue, cognition, myalgias, and arthralgias. Patients were placed into five groups according to time on treatment (1–4, 5–8, 9–12, 13–24, and 25–52 weeks), and changes in the primary symptoms as a function of time on treatment were analyzed using a mixed-effects proportional odds model.

Results

Among 158 patients with more than one follow-up visit who were monitored for up to 1 year, there were on average 6.7 visits per person (median 5, range 2–24). The last follow-up day was on average 96 days after enrollment (median 69, range 7–354 days), corresponding to the length of antibiotic therapy. Each primary symptom was significantly improved at one or more time points during the study. For cognition, fatigue, and myalgias, the greatest improvement occurred in patients on the longest courses of treatment (25–52 weeks) with odds ratios (OR) for improvement of 1.97 (P = 0.02), 2.22 (P < 0.01), and 2.08 (P = 0.01), respectively. In contrast, arthralgias were only significantly improved during the initial 1–4 weeks of therapy (OR: 1.57, P= 0.04), and the beneficial effect of longer treatment did not reach statistical significance for this symptom.

Conclusion

Prolonged intravenous antibiotic therapy is associated with improved cognition, fatigue, and myalgias in patients referred for treatment of neurologic Lyme disease. Treatment for 25–52 weeks may be necessary to obtain symptomatic improvement in these patients.

Keywords: Lyme disease, Borrelia burgdorferi, intravenous antibiotics, neurologic symptoms

Abstract

Video abstract

Video

Introduction

Lyme disease caused by the spirochete Borrelia burgdorferi is the most common tick-borne illness in the world today.14 Although prompt diagnosis and treatment results in a favorable outcome in patients with acute B. burgdorferi infection, tick exposure and acute infection with the Lyme spirochete often go unrecognized, and patients with untreated infection may go on to develop a chronic debilitating multisystem illness that is difficult to manage.14

The approach to the treatment of patients with persistent symptoms of Lyme disease has been controversial. The International Lyme and Associated Diseases Society (ILADS) advocates open-ended treatment linked to symptom resolution for what is considered to be a persistent spirochetal infection, claiming that the benefit of such treatment outweighs the risk.5 In contrast, the Infectious Diseases Society of America (IDSA) believes that persistent symptoms in these patients are due to “post-Lyme syndrome”, a noninfectious complication of acute spirochetal disease.6 According to the IDSA, treatment with prolonged antibiotics is considered inappropriate and even dangerous.610

In a previous prospective study, we showed that prolonged intravenous antibiotic therapy was associated with low morbidity and no mortality in closely monitored patients referred for treatment of neurologic Lyme disease.11 We have now examined the benefit of this therapy in a similar cohort of patients with neurologic Lyme disease symptoms.

Materials and methods

Patients

From April 2008 through August 2009, 225 consecutive patients were enrolled in this study. Patients from 18 states across the US were referred by their treating physicians to a single homecare company that administers intravenous antibiotic therapy in the outpatient setting. All patients had significant neuropsychiatric symptoms for at least 3 months and positive testing for B. burgdorferi, considered to be consistent with a diagnosis of neurologic Lyme disease by their treating physicians.1114 Neuropsychiatric symptoms included Bell’s palsy, meningoradiculitis, migraine, encephalopathy, mood disorders, and/or psychosis associated with tick exposure in a Lyme endemic area. Neurologic involvement was confirmed with brain magnetic resonance imaging, single-photon emission computed tomographic brain scans, and/or formal neuropsychiatric evaluation.1114 Serologic testing for B. burgdorferi was ordered and interpreted by the treating physicians.

Informed consent for intravenous antibiotic therapy and monitoring was obtained from all subjects, and the potential risks of extended parenteral therapy as well as the responsibility of patients to comply with the homecare treatment protocols were clearly defined, as previously described.11 Patients also agreed that information obtained from their treatment could be used for research purposes provided that strict confidentiality was maintained, as outlined in the guidelines of the US Department of Health and Human Services for observational studies (http://www.hhs.gov/ohrp/irb/irb_guidebook.htm). Consent forms acknowledging compliance with the Patient Bill of Rights and the Health Insurance Portability and Accountability Act guidelines were signed by all patients or their legal guardians. The study was granted exemption from review under 45 CFR 46.101(b)(4) by the Western Institutional Review Board, Olympia, WA, because it involved collection of data “in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects”.

Treatment protocol

Intravenous antibiotics were administered to all patients via an intravascular device using the SASH (saline/admixed drug/saline/heparin) protocol.11 This protocol involves initial infusion of a 10 mL normal saline flush to clear the line, then administration of the antibiotic in normal saline followed by a second 10 mL normal saline flush, and then 5 mL of heparin (100 units/mL) to maintain intravascular device patency. Dressing change and intravascular device assessment were performed on a weekly basis by homecare nurses, with monitoring for medication reactions and intravascular device infection, clotting, or infiltration according to the standard homecare protocol. Medication-related and catheter-related complications were immediately reported to the treating physician and the homecare service, and appropriate measures were taken to deal with the complication.

For the purpose of this study, only patients receiving intravenous ceftriaxone were included in the analysis. Patients with allergy to ceftriaxone were excluded from the study, and the ceftriaxone dose was determined by the treating physician. Patients on ceftriaxone therapy had liver function testing performed every 2 weeks, and ursodiol therapy was offered in conjunction with this antibiotic to prevent gallbladder toxicity. Probiotic therapy with daily oral acidophilus and/or saccharomyces was routinely recommended to all patients to prevent Clostridium difficile enterocolitis, as previously described.11 Ursodiol and probiotic therapy were dosed according to the manufacturer’s recommendations.15,16

Outcome measures

All patients completed a biweekly monitoring tool that assessed three broad symptom complexes, ie, pain, neurologic function, and general symptoms. The monitoring tool was developed during the previous safety study11 and contained questions about 28 separate symptoms. Participants were asked to rate each symptom’s severity and impact on their daily life as one of six ordinal classes, ie, 0 = not affected, 1 = slight, barely noticeable problem, 2 = minor yet noticeable problem, 3 = moderate problem, interferes with some daily activities, 4 = major problem, interferes with most daily activities, and 5 = disabling problem. Aside from measuring symptomatic changes, the use of the monitoring tool had two additional purposes, ie, to determine which symptoms caused the most functional disability and to mask the most significant symptoms in order to avoid response bias on the part of study participants who might focus on these symptoms.

Four symptoms were selected a priori as primary outcome measures in the study, and changes during treatment in these outcome measures were evaluated, ie, fatigue, cognition (“brain fog”), myalgias (muscle aches), and arthralgias (joint pain). These four symptoms comprised the most disabling factors for patients based on levels 4 and 5 ratings in the previous study. Questioning about these symptoms was randomly mixed with other questions in the monitoring tool.

Statistical analysis

Changes in the primary outcome measures as a function of time on treatment were analyzed using a mixed-effects proportional odds model (also referred to as a mixed-effects cumulative logit model), with measurement times nested within each participant.17 For each outcome, the validity of the proportional odds assumption was evaluated by fitting five mixed-effects binomial logistic models, categorizing the outcomes as 0 or 1, with each level used as a threshold, ie, 0 vs ≥1, ≤1 vs ≥2, ≤2 vs ≥3, ≤3 vs ≥4, and ≤4 vs 5. The log odds of the effects from each of the five models were examined using the point estimate and 95% confidence interval (CI). If the log odds for all of the five models appeared similar, then the proportional odds assumption was determined to represent the data well. If one or two models for a specific outcome had very different log odds, the ordinal classes were combined such that this assumption was met. If the assumption was not met, the model was not fit.

Each participant was placed into one of the five strata, based on duration of intravenous antibiotic treatment, and separate treatment effects were estimated for each patient stratum. Patient strata were 1–4 weeks (n = 32), 5–8 weeks (n = 33), 9–12 weeks (n = 28), 13–24 weeks (n = 37), and 25–52 weeks (n = 28) on intravenous therapy, resulting in patient groups with similar numbers of participants. To relax assumptions about the functional form of the relationship between treatment duration and symptom severity, time on intravenous treatment was categorized as 0–1 week, 1–4 weeks, 5–8 weeks, 9–12 weeks, 13–24 weeks, and 25–52 weeks. Treatment effectiveness by patient stratum expressed as the conditional odds and 95% CI of being in a lower (less severe) class are presented comparing responses during the final period of intravenous treatment with responses from first week on treatment.

The Akaike information criterion was used to measure the relative goodness of fit of the statistical model.18Three models were fitted to each outcome, and the result of the model with the lowest Akaike information criterion is presented. The three models include a factor variable for time on treatment, factors for time on treatment and patient stratum, and factors for time on treatment, patient stratum, and their interaction. The best model was confirmed using likelihood ratio tests.

Statistical analysis was performed using R 2.12.2 software (R Foundation for Statistical Computing, Vienna, Austria), and two-sided P values less than 0.05 were considered to be statistically significant.

Results

A total of 225 participants were initially enrolled in the study. In order to ensure treatment uniformity, only ceftriaxone-treated subjects with more than one visit over at least 1 week and up to 1 year of follow-up were included in the analysis. There were 158 patients who met these criteria (32 men and 126 women) accounting for 1051 study visits. The mean patient age was 41.1 (range 15–67) years. There were on average 6.7 visits (median 5, range 2–24) per person. The last follow-up day was on average 96 days after enrollment (median 69, range 7–354 days), corresponding to the length of antibiotic therapy. The number of participants in each stratum, based on duration of treatment, was similar: 32 patients were on treatment 1–4 weeks, 33 for 5–8 weeks, 28 for 9–12 weeks, 37 for 13–24 weeks, and 28 for 25–52 weeks.

Baseline scores for all outcomes are shown in Table 1. The scores for the 28 symptoms varied significantly, with patients showing a predominance of neurologic symptoms (74% with scores > 0) over non-neurologic symptoms (65% with pain scores > 0, 52% with systemic symptom scores > 0). This symptom distribution was consistent with the clinical diagnosis of neurologic Lyme disease made by the treating physician. However, the four target symptoms made up the majority of significant (levels 4 and 5) severity scores at baseline, ie, myalgias (41%), arthralgias (48%), fatigue (66%), and cognition (42%). Of the other 24 symptoms, only neck pain (37%), headache (35%), back pain (33%), and insomnia (32%) had similar severity scores.

Table 1

Baseline values of symptom severity

The baseline symptom severity scores stratified by duration of time on treatment are presented in Table 2. A likelihood ratio test showed significant differences in baseline scores according to patient stratum for the fatigue measure, with those on treatment for 9–12 and 13–24 weeks presenting with worse fatigue than the other groups. Baseline scores for the other three primary outcomes were not significantly different by treatment duration. The proportional odds assumption appears to have been met for all models after combining the highest two ordinal classes for cognition and joint pain and/or the lowest two ordinal classes for cognition.

Table 2

Baseline symptom severity for each follow-up duration group. Only those on follow-up of more than 1 week and less than 1 year are included

Table 3 shows the estimated changes in symptom severity at the end of treatment compared with the first week on treatment for each patient stratum. The severity of the four primary symptoms was significantly improved in at least one patient stratum (P < 0.05), and most P values were <0.10 in all groups for arthralgias, myalgias, and fatigue. For myalgias, arthralgias, and cognition, the model with the lowest Akaike information criterion included only the factor representing time on treatment; for fatigue it included both treatment duration and patient stratum. Those in treatment weeks 1–4 had significantly better arthralgia scores at the end of treatment compared with baseline, with the odds of being in a less severe ordinal group 1.57 times greater at the end of treatment compared with baseline (95% CI: 1.02–2.4). This corresponds to a 19% decrease in the proportion of patients reporting severe or disabling arthralgias after 1–4 weeks and a 17% drop after 25–52 weeks of treatment compared with baseline. Although the odds ratios were similar for the other participant groups, the effects were only marginally significant (<0.10).

Table 3

Changes in symptom severity by follow-up time group, at the time of the last follow-up visit

The severity of myalgias improved during the study as well, with more improvement seen in patients with longer duration of intravenous treatment. In those treated for 25–52 weeks, the odds of being in a less severe ordinal group were 2.08 (1.2–3.50) times greater at the end of treatment compared with baseline. This corresponds to about a 31% reduction in the proportion of patients reporting a major or disabling problem with myalgias (ordinal group 4 or 5) after 25–52 weeks of treatment compared with baseline.

The findings for fatigue were similar to those for myalgias, with improvement shown in all patient strata, and the most improvement occurring in patients on the longest courses of intravenous treatment. There was an estimated 22% reduction in the proportion of patients reporting disabling fatigue after 25–52 weeks of treatment compared with baseline. Significant improvement in cognition was only seen in the group on treatment for 25–52 weeks, with an odds ratio of being in a less severe symptom group of 1.97 (95% CI: 1.11–3.48) at the end of treatment compared with baseline. This corresponds to a 26% decline in the number of patients reporting cognitive problems to be disabling or a major problem at the end of treatment compared with baseline.

Discussion

Neurologic Lyme disease is characterized by neuropsychiatric symptoms that may be persistent and difficult to treat.1114 Intravenous antibiotic therapy is recommended for this condition, but the duration of prescribed treatment is controversial. While the IDSA guidelines recommend a maximum of 30 days of antibiotic therapy,6 the International Lyme and Associated Diseases Society guidelines take a more open-ended approach, tailoring therapy to resolution of patient symptoms.5 Although some studies have shown benefit of longer antibiotic therapy in neurologic Lyme disease,13,19 this therapy has been considered ineffective and even dangerous by IDSA.610 However, in a previous safety study, we showed that prolonged intravenous antibiotic therapy was associated with low morbidity and no mortality in closely monitored patients referred for treatment of neurologic Lyme disease.11 The mean length of treatment in that study was almost 4 months, and while the safety data was reassuring for that length of therapy, the study did not address the benefit of treatment given to those patients.

The present study evaluated the benefit of prolonged intravenous antibiotic therapy in patients diagnosed with neurologic Lyme disease by their treating physicians. The diagnosis of neurologic Lyme disease was supported by the symptom distribution recorded at baseline in these patients, as shown in Table 1. The predominance of women in our study population is consistent with previous observations that persistent Lyme disease is more commonly diagnosed in women.20 In contrast with our previous study, only patients receiving intravenous ceftriaxone were included in the analysis. As in the previous investigation, patients received an average of more than 3 months of intravenous antibiotic treatment, and they were closely monitored by homecare nurses. The treatment was associated with low morbidity and no mortality, confirming the safety of this therapy, as described previously.11

Previous controlled trials have examined relatively short intravenous antibiotic treatments ranging from 1–3 months for patients with neurologic Lyme disease.13,2123 A major criticism of these trials is that the length of treatment was insufficient to eradicate a persistent spirochetal infection. Our results indicate that prolonged antibiotic treatment for 25–52 weeks may be required to induce improvement in symptoms of neurologic Lyme disease. Although a control group was not included in the study, each patient had baseline symptom severity scores and multiple longitudinal measurements for up to 1 year, and the improvement in fatigue, myalgias, and cognition was significant with extended antibiotic therapy.

Numerous studies have documented persistent B. burgdorferi infection in patients with persistent symptoms of neurologic Lyme disease following short-course antibiotic therapy.14 Furthermore, animal models have demonstrated that short-course antibiotic therapy may fail to eradicate the Lyme spirochete.2426 Persistent spirochetal infection appears to be a more likely explanation for chronic symptoms of Lyme disease than the autoimmune hypotheses that have been postulated but never substantiated, and recent evidence has shed more light on the complex strategies that allow B. burgdorferito evade both the immune response and antibiotic agents.2729 The use of prolonged antibiotic therapy to eradicate ongoing spirochetal infection is consistent with the evidence for persistent B. burgdorferi infection outlined in these studies, and our results support this therapeutic approach.

Despite the negative view of prolonged antibiotic treatment for neurologic Lyme disease promoted by IDSA, antibiotic therapy ranging from 6 months to more than 5 years is recommended by infectious disease experts for a number of conditions, including drug-sensitive and drug-resistant tuberculosis, leprosy, disseminated atypical mycobacterial disease, brucella spondylitis, complicated actinomycosis, Whipple’s disease, Q fever endocarditis, and alveolar echinococcosis (Table 4).3034 Furthermore, intravenous antibiotic therapy beyond 30 days is routinely prescribed for osteomyelitis,35 and asplenia or hyposplenia in children is routinely treated prophylactically for 3–5 years with oral antibiotics,36,37 while daily macrolide therapy for up to 5 years was recently shown to prevent exacerbations of chronic obstructive pulmonary disease and post-transplant bronchiolitis obliterans.38 Thus, in certain conditions, the benefit of long-term therapeutic or prophylactic antibiotic therapy is thought to outweigh the risk. Our study suggests that prolonged antibiotic therapy may be required to improve the most disabling symptoms of neurologic Lyme disease, and taken together with our previous safety study, the risks of prolonged antibiotic treatment appear to be justifiable in these patients.

Table 4

Precedents for prolonged antibiotic therapy19,3034

Strengths of this study include the evaluation of significant symptoms that are common in neurologic Lyme disease. The study included a large number of participants, long duration of treatment, and multiple longitudinal measurements per participant. This allowed the use of a flexible statistical model structure, with separate effects estimated by treatment duration. Although the improvements in symptom severity observed in this study are encouraging and, in fact, necessary to infer a causal relationship between treatment and improvement, the lack of randomization into a control or placebo group prevents us from confirming a causal relationship. In addition, treatment duration was not defined a priori, and nonmedical factors such as financial considerations and insurance denial may have influenced treatment duration. These issues need to be addressed in a randomized controlled trial with antibiotic therapy administered beyond 3 months according to clinical need.

In summary, prolonged intravenous antibiotic therapy is associated with improved cognition, fatigue and myalgias in patients referred for treatment of neurologic Lyme disease. In contrast, improvement in arthralgias did not persist after 1–4 weeks of therapy. Treatment for 25–52 weeks may be necessary to obtain significant symptomatic improvement in patients with neurologic Lyme disease.

Acknowledgments

The authors thank Drs Joseph Brewer, Stephen Bunker, Michael Cichon, Steven Harris, Steven Meress, Deborah Metzger, Elizabeth Maloney, and Edward Winger for helpful discussion. We also thank Ramona Dandrilli, Tony Fernandez, Stephanie McCormick, and Teresa Wert for technical assistance, and Diane Blanchard, Phyllis Mervine, and Pat Smith for their continued support.

Footnotes

Disclosure

Funding for institutional review board review, data collection, and statistical analysis was provided by QMedRx Inc and Turn the Corner Foundation. RBS and CLG serve on the voluntary advisory panel for QMedRx Inc but have no financial ties to the company. SNC is a salaried employee of QMedRx Inc. AKD, VRS, and LJ have no conflicts of interest to declare in this work.

References

1. Johnson L, Stricker RB. Treatment of Lyme disease: A medicolegal assessment. Expert Rev Anti Infect Ther. 2004;2:533–557. [PubMed]
2. Harvey WT, Salvato P. ‘Lyme disease’: Ancient engine of an unrecognized borreliosis pandemic? Med Hypotheses. 2003;60:742–759. [PubMed]
3. Stricker RB, Johnson L. Lyme disease diagnosis and treatment: Lessons from the AIDS epidemic.Minerva Med. 2010;101:419–425. [PubMed]
4. Stricker RB, Johnson L. Lyme disease: The next decade. Infect Drug Resist. 2011;4:1–9.[PMC free article] [PubMed]
5. Cameron D, Gaito A, Harris N, et al. Evidence-based guidelines for the management of Lyme disease.Expert Rev Anti Infect Ther. 2004;2(1 Suppl):S1–S13. [PubMed]
6. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;41:1089–1134. [PubMed]
7. Ettestad PJ, Campbell GL, Welbel SF, et al. Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis. 1995;171:356–361. [PubMed]
8. Reid MC, Schoen RT, Evans J, Rosenberg JC, Horwitz RI. The consequences of overdiagnosis and overtreatment of Lyme disease: An observational study. Ann Intern Med. 1998;128:354–362. [PubMed]
9. Patel R, Grogg KL, Edwards WD, Wright AJ, Schwenk NM. Death from inappropriate therapy for Lyme disease. Clin Infect Dis. 2000;31:1107–1109. [PubMed]
10. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community- associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis. 2010;51:369–370. [PubMed]
11. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med. 2010;101:1–7. [PubMed]
12. Fallon BA, Nields JA. Lyme disease: A neuropsychiatric illness. Am J Psychiatry. 1994;151:1571–1583.[PubMed]
13. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70:992–1003. [PubMed]
14. Scelsa SN, Lipton RB, Sander H, Herskovitz S. Headache characteristics in hospitalized patients with Lyme disease. Headache. 1995;35:125–130. [PubMed]
15. Venneman NG, van Erpecum KJ. Gallstone disease: Primary and secondary prevention. Best Pract Res Clin Gastroenterol. 2006;20:1063–1073. [PubMed]
16. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101:812–822. [PubMed]
17. Gibbons RD, Hedeker D, DuToit S. Advances in analysis of longitudinal data. Annu Rev Clin Psychol.2010;6:79–107. [PMC free article] [PubMed]
18. Bozdogan H. Akaike’s information criterion and recent developments in information complexity. J Math Psychol. 2000;44:62–91. [PubMed]
19. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis. 2007;45:149–157. [PubMed]
20. Stricker RB, Johnson L. Gender bias in chronic Lyme disease. J Womens Health (Larchmt)2009;18:1717–1718. [PubMed]
21. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345:85–92. [PubMed]
22. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): A randomized double masked clinical trial. Neurology. 2003;60:1923–1930. [PubMed]
23. Oksi J, Nikoskelainen J, Hiekkanen H, et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: A double-blind, randomized, placebo-controlled, multicenter clinical study. Eur J Clin Microbiol Infect Dis. 2007;26:571–581. [PubMed]
24. Stricker RB, Johnson L. Persistent Borrelia burgdorferi infection after treatment with antibiotics and anti-tumor necrosis factor-alpha. J Infect Dis. 2008;197:1352–1353. [PubMed]
25. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52:1728–1736. [PMC free article][PubMed]
26. Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother. 2010;54:643–651. [PMC free article][PubMed]
27. Stricker RB, Johnson L. Searching for autoimmunity in “antibioticrefractory” Lyme arthritis. Mol Immunol. 2008;45:3023–3024. [PubMed]
28. Tunev SS, Hastey CJ, Hodzic E, Feng S, Barthold SW, Baumgarth N. Lymphoadenopathy during Lyme borreliosis is caused by spirochete migration-induced specific B cell activation. PLoS Pathog.2011;7:e1002066. [PMC free article] [PubMed]
29. Sapi E, Kaur N, Anyanwu S, et al. Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infect Drug Resist. 2011;4:97–113. [PMC free article][PubMed]
30. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med. 2001;345:189–200. [PubMed]
31. Bodur H, Erbay A, Colpan A, Akinci E. Brucellar spondylitis. Rheumatol Int. 2004;24:221–226.[PubMed]
32. Garner JP, Macdonald M, Kumar PK. Abdominal actinomycosis. Int J Surg. 2007;5:441–448. [PubMed]
33. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol. 2009;15:2078–2080.[PMC free article] [PubMed]
34. Liu YH, Wang XG, Gao JS, Qingyao Y, Horton J. Continuous albenda-zole therapy in alveolar echinococcosis: Long-term follow-up observation of 20 cases. Trans R Soc Trop Med Hyg. 2009;103:768–778. [PubMed]
35. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: What have we learned from 30 years of clinical trials? Int J Infect Dis. 2005;9:127–138. [PubMed]
36. Price VE, Blanchette VS, Ford-Jones EL. The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am. 2007;21:697–710. viii–ix. [PubMed]
37. Beytout J, Tournilhac O, Laurichesse H. Antibiotic prophylaxis in splenectomized adults. Presse Med.2003;32(28 Suppl):S17–19. French. [PubMed]
38. Vos R, Vanaudenaerde BM, Verleden SE, Van Raemdonck DE, Dupont LJ, Verleden GM. Azithromycin in posttransplant bronchiolitis obliterans syndrome. Chest. 2011;139:1246–1247. [PubMed]

Articles from International Journal of General Medicine are provided here courtesy of Dove Press

Treatment for Lyme Desease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003502/

Treatment of Lyme borreliosis

This article has been cited by other articles in PMC.

Abstract

Borrelia burgdorferi sensu lato is the causative agent of Lyme borreliosis in humans. This inflammatory disease can affect the skin, the peripheral and central nervous system, the musculoskeletal and cardiovascular system and rarely the eyes. Early stages are directly associated with viable bacteria at the site of inflammation. The pathogen-host interaction is complex and has been elucidated only in part. B. burgdorferi is highly susceptible to antibiotic treatment and the majority of patients profit from this treatment. Some patients develop chronic persistent disease despite repeated antibiotics. Whether this is a sequel of pathogen persistence or a status of chronic auto-inflammation, auto-immunity or a form of fibromyalgia is highly debated. Since vaccination is not available, prevention of a tick bite or chemoprophylaxis is important. If the infection is manifest, then treatment strategies should target not only the pathogen by using antibiotics but also the chronic inflammation by using anti-inflammatory drugs.

Introduction

In recent decades much has been learned about the aetiology of Borrelia burgdorferi infection and the transmitting arthropod, the tick. The exact pathogenesis, however, especially of late-stage manifestations of Lyme disease, is far from clear. Several models of disease pathogenesis and the treatment options are being debated controversially. This debate is reflected in a significant uncertainty of how to treat long-term manifestations of the disease in particular. The authors of the present review have tried to summarise what is known about disease aetiology, pathogenesis and treatment from these different perspectives in order to provide a basis for future discussions.

Clinical disease and pathogenesis of Lyme disease

Borrelia species, the transmitting vectors and early skin manifestations

Lyme borreliosis in adults has been divided into three clinical stages [1,2]. The early manifestations of the infection mainly involve the skin and the nervous system. At the site of the tick bite an erythema migrans regularly develops, but can be absent in up to 20 to 50% of patients [3] depending on the region of the reports. The skin lesion is infrequently accompanied by unspecific symptoms of a systemic infection, including malaise, fatigue, headache, fever and regional lymphadenopathy.

In the USA, erythema migrans seems to be present more regularly than in Europe; it has been associated with a comparably more intense inflammation and a systemic spread of the pathogen, which might reflect that in the USA only one species of B. burgdorferi sensu lato – namely B. burgdorferi sensu strictu – is responsible, whereas in Europe further species – Borrelia afzelii and Borrelia garinii, and recently Borrelia spielmanii [4,5] – have been identified. Another early skin manifestation, Borrelia lymphocytoma (lymphadenosis cutis benigna) – a purple nodular lesion affecting the ear, the nose or the breast nipple – has only been reported in European patients [6]. This may again reflect the presence of different regionalBorrelia genotypes and/or strains.

Despite these differences in aetiology, the clinical manifestations are otherwise quite comparable. A few weeks to months after the pathogen has been transferred from the vector, especially Ixodes ticks, to the human host, several organs may become affected, probably because of a haematogenous spread of the pathogen. The arthropod vector differs geographically. In Europe Ixodes ricinus is transmitting the pathogen, whereas in America the transmitting species is Ixodes scapularis.

Early dissemination of the pathogen

The next phase of disease is denominated early dissemination. A systemic disease evolving out of a single erythema migrans lesion has been reported in up to 40% of affected children. About 25% of children with rare multiple erythema migrans do have cerebrospinal fluid (CSF) pleocytosis, demonstrating a clinically nonovert dissemination of the pathogen into the central nervous system (CNS) [7].

Aside from this systemic dissemination into the skin, early dissemination mainly affects the nervous system – presenting as meningitis (CSF pleocytosis) and cranial neuritis predominantly in children. Meningoradiculoneuritis (Bannwarth’s syndrome) and plexus neuritis are reported less frequently. The involvement of the heart was documented as atrioventricular blockade, myopericarditis and cardiomyopathy, but seems to be rare in both Europe and North America [8]. Early musculoskeletal complaints are reported frequently in the United States, and are less frequent in Europe. The musculoskeletal system can be involved with mild arthralgia and myalgia, in addition to a mild oligoarthritis.

In children, early dissemination and especially neuroborreliosis usually occurs earlier than in adults. This might be due to a different site of the tick bite. In children the upper trunk and the head are selected more often by the tick than in adults, potentially making the CNS more accessible to the spirochete [9].

Late stages of Lyme disease

The late stages of disease appearing months to years after infection are somewhat comparable between children and adults. In children, however, the affection of the skin and CNS are rarely seen [10]. Episodic or chronic oligoarthritis is the most frequent manifestation [11]. Neurological manifestations, more frequent in adulthood (polyneuropathy, encephalomyelitis, cranial neuropathy), are hardly recognised in children [12]. Rarely, uveitis and keratitis have been reported as late manifestations [13]. Among untreated patients in the USA, around 60% begin to have intermittent attacks of joint swelling and pain. The knees and other large joints are especially affected [1,14]. Synovial inflammation/arthritis usually is nonerosive, but can be erosive with cartilage and joint destruction – especially with chronic, persistent antibiotic-refractory arthritis. Left untreated, arthritis does show a prolonged course with a gradual, spontaneous resolution after several (up to 6) years [11]. Late skin manifestations have long been described as Acrodermatitis chronica atrophicans. Of interest, this condition has only been reported occasionally in adolescents.

Strategies proven to be effective in the treatment of Lyme borreliosis in one geographic location are often extrapolated to other regions in which the Borrelia species may differ and predominant clinical manifestations may vary. Because the natural history of untreated Lyme borreliosis is not delineated for all regions, it is difficult to assess whether these treatment regimens are equally efficacious across geographic regions without additional controlled studies. In addition, other tick-transmitted infections, such as babesiosis, human granulocytic ehrlichiosis and southern tick-associated rash illness, may complicate the diagnosis and treatment response, especially in the case of coinfections [15,16].

Some patients treated with antibiotics for Lyme arthritis do not experience a resolution of their arthritis, even after more than one course of treatment. The pathogenesis of this condition is not elucidated. Several hypotheses exist. Antibiotic-treatment-refractory Lyme arthritis might be rooted in a persistent infection of the pathogen suggested by the presence of borrelial DNA [17], retained spirochetal antigens with no living bacteria present [18], a pathogen-induced autoimmunity resulting from a T-cell-receptor epitope mimicry [1921] or, finally, a nonspecific bystander immune activation. In individual patients, a predefined rheumatological auto-immunity might be unmasked by borrelial infection. In this regard, a predominance of HLA alleles DR4 and DRB1 has been associated both with chronic Lyme arthritis and adult rheumatoid arthritis in the USA [1]. In Europe, however, such an HLA association has not been elicited in affected adults and children [22,23].

The concept of molecular mimicry was suggested several years ago by identification of leukocyte function associated antigen 1 alpha as a candidate auto-antigen, which might cross-react with an outer surface protein A peptide epitope in treatment-refractory Lyme arthritis patients who express HLA-DRB1*0401 [19,21]. This concept would suggest a reactive type of arthritis being present in Lyme disease. Of particular interest is the capability of the pathogen to interact with the human immune system. At first, the innate immune system is capable of detecting the infection [24]. Sequentially the adaptive immune system is attacking the pathogen by B. burgdorferi-specific antibodies targeting various outer surface and structural proteins. B. burgdorferi is capable, however, of eliciting a variety of survival strategies inside the human host in order to circumvent the innate and the adaptive immune system. These strategies include complement resistance, antigen variation, lateral gene transfer and lipoprotein polymorphism [25]. In addition, the pathogen itself may be able to persist inside human phagocytic or tissue resident cells in vitro[25,26]. In the human organism, however, such a long-term persistence seems to be, if present at all, a very rare event, even though it has been suggested by some occasional case reports [27,28]. It is of interest, however, in patients with chronic treatment-refractory arthritis that B. burgdorferi DNA has been detected in synovial tissue, but not in synovial fluid samples even after repetitive antibiotic treatments [17]. Whether this reflects the actual presence of a viable pathogen is unclear at the moment, but is controversially debated [29].

Morphological changes of B. burgdorferi into the shape of cystic structures have been described in experimental environmental conditions. Again, whether this is of relevance in vivo has not been elucidated [30]. In a recent detailed structural analysis of brain tissue samples spirochetal or cystic structures have been reported in patients affected by neuroborreliosis. Control tissue of chronic brain inflammation other than borreliosis was not provided, however, limiting the evaluation of these findings [31].

There certainly is a consensus that an antibiotic treatment is of relevance in every different stage of Lyme borreliosis. What is the basis for this consensus and are there needs for a treatment beyond that?

Current treatment of Lyme disease

Prevention of Lyme borreliosis

Prevention of Lyme borreliosis after a tick bite has been reported using a single dose of doxycycline as chemoprophylaxis in America [32]. In Europe, however, a comparable prophylactic treatment has not been evaluated with regard to I. ricinus tick bites. The best prophylactic strategy is to avoid a tick bite. A rapid removal of a tick within 6 hours (I. ricinus) to 24 hours (I. scapularis) has been suggested [33]. The use of protective clothing and of tick repellents is advised, but this is beyond the scope of the present review.

Treatment of early manifestations

Early descriptions from America suggested that an erythema migrans can resolve spontaneously within 6 weeks, but an antibiotic treatment can shorten its duration to a few days [34]. Since then treatment studies have no longer included a placebo arm. Antibiotic treatment using doxycycline, amoxicillin, penicillin, cefuroxime axetil, ceftriaxone and recently azithromycin was focused on the outcome. In particular, an equal effectiveness in avoiding late manifestations has been shown by treatment of erythema migrans with doxycycline, amoxicillin and cefuroxime axetil for 14 days (Table ​(Table1)1) [35]. Oral antibiotics seem to be a sufficient treatment for solitary erythema migrans without signs of systemic disease. Extending the treatment with doxycycline from 10 to 20 days or adding an additional dose of ceftriaxone at the beginning did not improve the therapeutic efficacy in patients with erythema migrans [36]. A subsequent late stage of Lyme disease can therefore be prevented effectively by treating erythema migrans with antibiotics [37]. Since doxycycline can only be used in childhood starting at the age of 8 years and because of frequent allergies involving penicillin derivatives, azithromycin has been evaluated for the treatment of early Lyme disease. Owing to the longer half-life, treatment duration has been limited to 5 days. Even though Massarotti and colleagues found azithromycin to be equally effective for the treatment of early Lyme disease [38], Luft and colleagues considered azithromycin to be inferior when compared with amoxicillin [39].

Table 1

Antibiotic therapy for early Borrelia burgdorferi infection

Overall, antibiotic treatment studies in Europe did reveal results comparable with the US examinations. Erythema migrans takes somewhat longer to resolve, however, which has been associated with the presence of three different Borrelia species in Europe [6,40].

About 25 to 70% of patients with erythema migrans develop nonspecific symptoms including fatigue, headache, arthralgia and myalgia, fever and lymphadenopathy, suggesting a systemic dissemination of the pathogen. In America this early dissemination is reflected in part by the presence of multiple annular skin lesions, a rare phenomenon in Central Europe. In patients with acute disseminated Lyme disease (excluding patients with meningitis, but with an erythema migrans present, in addition to signs of disease dissemination), oral doxycycline for 21 days was equally as effective in preventing late manifestations of disease as intravenous ceftriaxone for 14 days [41]. Wormser suggested that erythema migrans with uncomplicated facial nerve palsy can be treated with a 14-day course of antibiotic treatment using oral doxycycline, amoxicillin or cefuroxime in adulthood [35]. If a significant heart involvement or meningitis is present with erythema migrans, however, an intravenous antibiotic treatment regimen using ceftriaxone or cefotaxime was recommended for 14 days [35].

In paediatric patients the response to first-line treatment has been comparable with that of adults. Oral amoxicillin has been shown to be as effective as cefuroxime axetil [42]. In addition, phenoxymethylpenicillin has been shown to be effective in solitary erythema migrans [43]. The use of doxycycline after the age of 8 years has been considered reasonable in early stages of Lyme disease also in children.

Most patients treated for early cutaneous Lyme borreliosis have an excellent prognosis, although some patients treated for erythema migrans continue to have a variety of complaints after antibiotic therapy in recent series. Coinfection with infectious agents other than B. burgdorferi has been considered in this regard [44]. Coinfection in general, however, seems to be a rare event even in populations at high risk – it cannot be regarded as a general phenomenon [45,46]. There are no data that chronic Lyme borreliosis is associated with coinfections.

Early B. burgdorferi dissemination

In the second phase of infection about 15% of patients develop an acute neuroborreliosis a few weeks to months after the tick bite. Typical symptoms are cranial neuritis including Bell’s palsy, meningitis and radiculitis. They are caused by meningeal inflammation, which can be accompanied by a significant headache or pain radiating into the extremities. The clinical picture of the second stage seems comparable throughout the world. In children, however, lymphocytic pleocytosis and facial nerve palsy seem to be much more common than radiculitis [47]. There are sufficient treatment reports to conclude that infection of the nervous system in both adults and children can be treated with penicillin, ceftriaxone and cefotaxime intravenously as well as doxycycline orally (Table ​(Table2).2). Although parenteral treatment regimens for neuroborreliosis are generally preferred, several European studies support the use of oral doxycycline with a noncomplicated CNS involvement [48].

Table 2

Therapy for late stages of Borrelia burgdorferi infection or inflammation

In very rare cases, encephalomyelitis – and especially transverse myelitis – has been reported in childhood [12]. An intravenous antibiotic treatment for 14 days was effective in treating these children. Since CNS involvement in children can occur quite early (within a few days) after a tick bite, a previously Borrelia-nonexposed host might not be able to mount a detectable antibody response against the pathogen in such a short time [49]. Pleocytosis or facial palsy due to Borrelia might therefore not be distinguishable from other infectious causes like Mycoplasma or herpes virus infections, because serology can be unremarkable [49]. At this time, the physician might consider an additional macrolide antibiotic or antiviral treatment, especially if there are no signs of improvement during antimicrobial treatment with β-lactams [50].

In addition, corticosteroids have been recommended in Bell’s palsy [50]. The authors have not found reports that corticosteroid treatment proved harmful in patients with Bell’s palsy who were diagnosed with Lyme disease subsequently. Nevertheless, the usage of corticosteroids in patients with facial paralysis and highly suspected Lyme aetiology cannot be recommended and has to be considered with caution. The long-term outcome of noncomplicated neuroborreliosis (facial paralysis or pleocytosis) seems to be quite good, with minor residual facial palsies in up to 20% of patients. Cerebrovascular neuroborreliosis with signs of vasculitis and cerebral ischemia has rarely been reported in children [51].

Late stages of Lyme disease

Arthritis

In the early days of therapeutic approaches in Lyme arthritis, only very few studies have been performed in which a fraction of patients was left untreated or was treated with placebo. These patients seemed to have a prolonged course of arthritis when compared with the antibiotic-treated (penicillin or ceftriaxone) patients [11]. Nontreated patients with Lyme arthritis have been reported to suffer from ongoing chronic or episodic arthritis, or progress to other late manifestations including keratitis and chronic encephalopathy [52].

Some indirect evidence has been gathered that antibiotic treatment is indeed targeting a persistent infection: patients with antibiotic-responsive arthritis did show a decline in antibody titres to B. burgdorferi, whereas antibody titres remained high in patients who were left untreated. Patients who presented with persistent arthritis despite antibiotic treatment also showed a decline in antibody titres. This suggested that synovial inflammation persisted in these patients after the infection was cleared by the use of antibiotics [53]. The studies conducted, however, have not tried to evaluate a principal anti-inflammatory effect of antibiotics. Steere and Angelis reported on their initial, untreated Lyme arthritis cohort. Arthritis eventually resolved after a disease duration of about 6 years or longer in children, adolescents and adults [11]. In the author’s own experience, however, there are a few patients who eventually continue to have chronic arthritis despite several antibiotic treatments according to European guidelines [54]. In these patients, local inflammation stays active and significant antirheumatic treatment strategies are necessary. Which particular patient does not benefit from antibiotic treatment and who is prone to proceed to long-term Lyme arthritis is not clear. As already mentioned, immunological features, genetic factors and pathogen-related factors might all contribute to the evolution into a rheumatoid-like disease. Even though a significant portion of treatment-refractory patients with Lyme arthritis has been noted in several studies, the general consensus is that antibiotic treatment remains the cornerstone of therapy [11,40].

Steere and Angelis recently formulated a treatment algorithm for the diagnosis and treatment of Lyme arthritis. As an initial treatment they suggest using oral doxycycline or oral amoxicillin for 30 days. They proposed a repetition of the oral antibiotic regimen for another 30 days if a mild arthritis persists after the first-line treatment was completed 30 days ago. An intravenous antibiotic treatment using ceftriaxone, cefotaxime or penicillin for 30 days was recommended if a moderate to severe arthritis persists. The basis for this suggestion, especially the reason for the prolongation of treatment up to 30 days, was not made clear. This suggestion has to be considered an expert opinion [11]. In comparison, other authors have reported that penicillin G is not as effective as ceftriaxone for the treatment of late Lyme manifestations [55].

Significant side effects using an intravenous treatment strategy for longer than 14 days have to be considered. The authors of the present review suggested a repetition of antibiotic therapy in antibiotic-refractory Lyme arthritis for the duration of 14 days with a preference of using intravenous cefotaxime in an inpatient setting (three divided doses) [54]. Cefotaxime seems to have lesser side effects than ceftriaxone with regard to complications of bile secretion.

In an outpatient setting, intravenous ceftriaxone for the duration of 14 days would be the first choice (one daily dose). Reviewing the work of Steere and Angelis, a significantly greater number of doxycycline-treated patients (45 out of 71) did respond to therapy when compared with five out of 46 patients who responded after intravenous ceftriaxone. This remarkable failure rate using ceftriaxone as a first-line agent was left unexplained [11]. For children older than 8 years of age, arthritis can be treated using doxycycline in a dose of 4 mg/kg/day [54] (Fig. ​(Fig.1).1). From a rheumatological point of view, it is striking that in almost all of the Lyme arthritis studies reported, no concomitant anti-inflammatory therapy has been evaluated. Our experience is that the parallel usage of nonsteroidal anti-inflammatory drugs right from the beginning does reduce symptoms of inflammation and contributes to a faster resolution of arthritis, even though no prospective long-term data are available.

Figure 1

In vitro antimicrobial susceptibility of Borrelia burgdorferisensu strictu. Reduction of viable spirochetes in the presence of different concentrations of antibiotics (ceftriaxone, doxycycline). Cotrimoxazole, which is considered ineffective, is used 

In children and adolescents, treatment guidelines in Europe do include the usage of nonsteroidal anti-inflammatory drugs in parallel to antibiotics. There was a consensus that the second round of antibiotic treatment should not exceed a time period of 14 days with intravenous antibiotics or 4 weeks with oral doxycycline [54]. If arthritis persists after two complete courses of antibiotic treatment and sufficient non-steroidal anti-inflammatory drug treatment, intra-articular steroids and the use of disease-modifying antirheumatic drugs should be considered [54]. Arthroscopic synovectomy has been reported occasionally [11]. A further prolongation of the antibiotic treatment was suggested in case the synovial fluid or tissue analysis does reveal the presence of B. burgdorferi DNA. This suggestion can be considered of expert level and is not based on controlled studies [11]. It is not clear whether such a positive PCR represents the presence of a viable pathogen or simply nondegraded DNA, and whether this finding is of clinical relevance.

A prospective treatment study was reported from a European childhood cohort in 1995 [23]. The response rate after one or two courses of different antibiotics resulted in a disappearance of arthritis in 77% of the patients [56]. Szer and colleagues reported on the long-term follow-up of patients initially followed by Steere and colleagues who were not treated with antibiotics. Only a few patients were reported to suffer from ongoing chronic or episodic arthritis, or progress to other late manifestations including keratitis and chronic encephalopathy [52]. The scarcity of the studies on long-term outcome does reflect an urgent need to perform follow-up studies even on a retrospective basis. In addition, a long-term prospective controlled trial is warranted in order to further elucidate the beneficial role of antibiotics in children. It seems reasonable to consider conventional anti-inflammatory drug treatment for arthritis already from the start together with antibiotics.

Late neurological disease

Peripheral polyneuropathy (paresthesia), meningoradiculoneuritis (radicular pain), encephalopathy (memory loss, mood changes, sleep disturbance) or encephalomyelitis do represent late neurological manifestations in adulthood [57]. Treatment efforts using antibiotics (Table ​(Table3)3) usually are effective [57]. In childhood, neurological disease is predominantly an early manifestation (CSF pleocytosis, facial palsy) but also can present as radiculitis in older children [58]. Late manifestations have to be considered very rare.

Table 3

Therapy for persistent Lyme arthritis refractory to the first antibiotic treatment

Late skin disease

Late skin manifestations are usually caused by B. garinii and B. afzelii, and are thus seen predominantly in Europe and not in the USA. Acrodermatitis chronica atrophicans is caused by B. afzelii and is characterised as a blue/red-coloured atrophic skin lesion predominantly at the extremities [59]. Antibiotic therapy for at least 4 weeks has been recommended (Table ​(Table3)3) [60].

Post-Lyme disease syndrome

Despite the resolution of Lyme borreliosis manifestations after antibiotic treatment in the majority of patients, a minority of patients present fatigue, musculoskeletal pain, concentration or short-term memory problems. These generally mild and self-limiting symptoms have been termed post-Lyme disease symptoms. If the symptoms last longer than 6 months they have been called post-Lyme disease syndrome.

In contrast to the late manifestations of antibiotic-refractory arthritis and post-Lyme disease symptoms/syndrome, there is a group of patients with chronic pain, neurocognitive symptoms, fatigue, and so forth. In some of these patients the diagnosis of chronic Lyme disease has been made without clinical or serological evidence of a current or previous Lyme disease. There have been attempts to define the pathogenesis of this particular complex of symptoms. Not yet standardised diagnostic tests to detect B. burgdorferi immunoreactivity have often been implemented. Recent studies, which have tried to define these patients more clearly, in general point towards other causative differential diagnoses including fibromyalgia or other autoimmune musculoskeletal diseases [6163]. Intravenous or oral antibiotics for a prolonged period of time or repetitively did not improve symptoms in these particular patients [61]. Nevertheless there is still a major controversy in the literature and in the press requesting long-term antibiotic treatment for these patients [29,64].

To make things difficult, a few arthritis patients have been described with evidence that B. burgdorferi DNA persisted in the joint without anti-B. burgdorferi antibodies present in their peripheral blood [65]. The cause of seronegativity is unknown. One possible cause might be the formation of immune complexes involving antigen-specific antibodies. Since routine serodiagnostic tests rely on free antibodies, antibodies tied up in complexes would not be detectable [66]. In the majority of patients suffering from late Lyme disease, however, a robust antibody response is present. There might be only very few individuals affected by Lyme arthritis or post-Lyme disease syndrome who do not have a detectable serological response to the pathogen. Seronegative patients without clinical signs of classical Lyme disease but with chronic fatigue, arthralgia and myalgia did not respond to antibiotics even when multiple courses of treatments were given. This study was also interpreted in a way that serological tests can reliably rule out Lyme borreliosis in patients with these chronic symptoms, thus preventing unnecessary treatment with antibiotics [67]. For the majority of chronic Lyme disease patients, other differential diagnoses should be considered. This could avoid long-term, and therefore potentially side-effect-prone, antibiotic treatment. As can be expected, there is a lot of controversy on the subject of chronic Lyme disease [29,62,68].

Strategies to generate a vaccine against Borrelia

Several significant obstacles have to be overcome before a vaccine can be considered effective in the context of the complex tick-host-pathogen interaction in Lyme borreliosis. B. burgdorferi is able to mount molecular survival strategies in order to circumvent the host’s immune defence mechanisms [25]. In addition, persistence in bradytrophic tissues might render the pathogen inaccessible for the immune system [27].

B. burgdorferi not only manipulates human resident tissue cells and members of the immune system, but also interacts with the gene expression profile of the tick vector. The latter strategy enables the pathogen to survive within the tick and during the transmission process. Some of these tick gene products might be potentially valuable in developing a vector-antigen-based vaccine [69]. These vector-based vaccine targets, however, are just at the beginning of being evaluated.

In the early 1990s, the major outer-surface protein (Osp) A and OspB were already considered interesting targets for a pathogen-based vaccine [70]. Since only one B. burgdorferi genotype is present in the United States, two recombinant OspA vaccine preparations were eventually tested in adults as well as in children – the vaccines were considered safe and their immunogenicity to be sufficient to mount an anti-OspA immune response [71]. It was of particular immunological interest that the recombinant OspA vaccine was able to block transmission of the spirochete from the vector to the host by virtually sterilising the infected vector. During the blood feast, OspA-specific antibodies were transferred from the immunised host to the vector. These transferred antibodies did interfere with the complex lifecycle of the spirochetes, which express OspA especially inside the tick. Success of the vaccine in murine animal models [72] was the basis for these human studies [73]. Subsequent analyses of the cost-effectiveness revealed that individuals who live in areas where Lyme disease is endemic and who are frequently exposed to ticks are the best candidates to be vaccinated [74]. Despite clinical effectiveness and no significant side effects reported, Lyme disease vaccines have been taken off the market or are no longer propagated. Fears that an OspA-based vaccine could itself induce an autoimmune disease by induction of a cross-reactive immune response might have contributed to low sales of the vaccine and its final withdrawal from the market.

Owing to the presence of several Borrelia genotypes in Europe, a monovalent vaccine is not considered effective throughout Europe. Different vaccine targets therefore have to be considered. In addition, due to molecular strategies of the Lyme disease spirochete B. burgdorferi, including antigenic variation and immune escape, complement resistance as well as lateral gene transfer, one particular preventive strategy seems insufficient to induce long-term protection [25].

Conclusion

Even though Lyme borreliosis is considered an infection, and despite high antibiotic sensitivity of the pathogen, a limited number of patients treated for late-stage disease remain symptomatic despite antibiotics. The reason for persistent symptoms is unclear. Several pathogen-related and host-related factors have been suggested. There is considerable lack of knowledge on the natural course of disease in different environments and with regard to different genotypes or even strains of B. burgdorferi sensu lato. Coinfections may complicate the picture even further.

Current knowledge of the effectiveness of antibiotic treatment strategies is based on a very limited number of trials, which have not been evaluated sufficiently long term and which often lack a placebo-controlled arm. In addition, the number of patients included has to be considered limited, as no large double-blind, controlled, long-term prospective trials have been performed. Unsurprising, therefore, is the considerable uncertainty of which antibiotic regimen should be chosen and which duration of therapy should be performed. For the time being, guidelines for antibiotic treatment have been suggested that are successful in about 80% of patients affected by late stages of B. burgdorferi infections.

Overall, the outcome of early and late manifestations seems to be good; nevertheless, there is an urgent need to develop strategies for those patients who do not respond completely to the current treatment concepts.

Abbreviations

CNS: central nervous system; CSF: cerebrospinal fluid; Osp: outer surface protein; PCR: polymerase chain reaction.

Competing interests

The authors declare that they have no competing interests.

References

  • Steere AC, Glickstein L. Elucidation of Lyme arthritis. Nat Rev Immunol. 2004;4:143–152.[PubMed]
  • Singh SK, Girschick HJ. Lyme borreliosis: from infection to autoimmunity. Clin Microbiol Infect.2004;10:598–614. [PubMed]
  • Hengge UR, Tannapfel A, Tyring SK, Erbel R, Arendt G, Ruzicka T. Lyme borreliosis. Lancet Infect Dis. 2003;3:489–500. [PubMed]
  • Maraspin V, Ruzic-Sabljic E, Strle F. Lyme borreliosis and Borrelia spielmanii. Emerg Infect Dis.2006;12:1177. [PMC free article] [PubMed]
  • Herzberger P, Siegel C, Skerka C, Fingerle V, Schulte-Spechtel U, van Dam A, Wilske B, Brade V, Zipfel PF, Wallich R, Kraiczy P. Human pathogenic Borrelia spielmanii sp. nov. resists complement-mediated killing by direct binding of immune regulators factor H and factor H-like protein 1. Infect Immun. 2007;75:4817–4825. [PMC free article] [PubMed]
  • Stanek G, Strle F. Lyme disease: European perspective. Infect Dis Clin North Am. 2008;22:327–339. vii. [PubMed]
  • Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med. 1996;335:1270–1274. [PubMed]
  • Manzoor K, Aftab W, Choksi S, Khan IA. Lyme carditis: sequential electrocardiographic changes in response to antibiotic therapy. Int J Cardiol. 2009;137:167–171. [PubMed]
  • Huppertz HI, Girschick HJ. Lyme borreliosis. Pediatrics in systemic autoimmune diseases. Vol. 6. Amsterdam: Elsevier BV; 2003.
  • Huppertz HI, Bohme M, Standaert SM, Karch H, Plotkin SA. Incidence of Lyme borreliosis in the Wurzburg region of Germany. Eur J Clin Microbiol Infect Dis. 1999;18:697–703. [PubMed]
  • Steere AC, Angelis SM. Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum. 2006;54:3079–3086. [PubMed]
  • Latsch K, Tappe D, Warmuth-Metz M, Hebestreit H. Central nervous system borreliosis mimicking a pontine tumour. J Med Microbiol. 2006;55(Pt 11):1597–1599. [PubMed]
  • Huppertz HI, Munchmeier D, Lieb W. Ocular manifestations in children and adolescents with Lyme arthritis. Br J Ophthalmol. 1999;83:1149–1152. [PMC free article] [PubMed]
  • Steere AC, Duray PH, Butcher EC. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue. Arthritis Rheum.1988;31:487–495. [PubMed]
  • Singh SK, Girschick HJ. Tick-host interactions and their immunological implications in tick-borne diseases. Curr Sci. 2003;85:1284–1298.
  • Hoppa E, Bachur R. Lyme disease update. Curr Opin Pediatr. 2007;19:275–280. [PubMed]
  • Priem S, Burmester GR, Kamradt T, Wolbart K, Rittig MG, Krause A. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Ann Rheum Dis. 1998;57:118–121.[PMC free article] [PubMed]
  • Honegr K, Hulinska D, Dostal V, Gebousky P, Hankova E, Horacek J, Vyslouzil L, Havlasova J. Persistence of Borrelia burgdorferi sensu lato in patients with Lyme borreliosis. Epidemiol Mikrobiol Imunol. 2001;50:10–16. [PubMed]
  • Gross D, Huber BT, Steere AC. Molecular mimicry and Lyme arthritis. Curr Dir Autoimmun.2001;3:94–111. [PubMed]
  • Drouin EE, Glickstein LJ, Steere AC. Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato. J Autoimmun. 2004;23:281–292. [PubMed]
  • Drouin EE, Glickstein L, Kwok WW, Nepom GT, Steere AC. Searching for borrelial T cell epitopes associated with antibiotic-refractory Lyme arthritis. Mol Immunol. 2008;45:2323–2332.[PMC free article] [PubMed]
  • Reimers CD, Neubert U, Kristoferitsch W, Pfluger KH, Mayr WR. Borrelia burgdorferi infection in Europe: an HLA-related disease? Infection. 1992;20:197–200. [PubMed]
  • Huppertz HI, Karch H, Suschke HJ, Doring E, Ganser G, Thon A, Bentas W. Lyme arthritis in European children and adolescents. The Pediatric Rheumatology Collaborative Group. Arthritis Rheum. 1995;38:361–368. [PubMed]
  • Singh SK, Girschick HJ. Toll-like receptors in Borrelia burgdorferi-induced inflammation. Clin Microbiol Infect. 2006;12:705–717. [PubMed]
  • Singh SK, Girschick HJ. Molecular survival strategies of the Lyme disease spirochete Borrelia burgdorferi. Lancet Infect Dis. 2004;4:575–583. [PubMed]
  • Girschick HJ, Huppertz HI, Russmann H, Krenn V, Karch H. Intracellular persistence of Borrelia burgdorferi in human synovial cells. Rheumatol Int. 1996;16:125–132. [PubMed]
  • Haupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonherr U, Kalden JR, Burmester GR. Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum. 1993;36:1621–1626. [PubMed]
  • Honegr K, Hulinska D, Beran J, Dostal V, Havlasova J, Cermakova Z. Long term and repeated electron microscopy and PCR detection of Borrelia burgdorferi sensu lato after an antibiotic treatment. Cent Eur J Public Health. 2004;12:6–11. [PubMed]
  • Ballantyne C. The chronic debate over Lyme disease. Nat Med. 2008;14:1135–1139. [PubMed]
  • Alban PS, Johnson PW, Nelson DR. Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi. Microbiology. 2000;146(Pt 1):119–127. [PubMed]
  • Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL. Persisting atypical and cystic forms ofBorrelia burgdorferi and local inflammation in Lyme neuroborreliosis. J Neuroinflammation.2008;5:40. [PMC free article] [PubMed]
  • Wormser GP, Dattwyler RJ, Shapiro ED, Dumler JS, O’Connell S, Radolf JD, Nadelman RB. Single-dose prophylaxis against Lyme disease. Lancet Infect Dis. 2007;7:371–373. [PubMed]
  • Wormser GP. Prevention of Lyme borreliosis. Wien Klin Wochenschr. 2005;117:385–391.[PubMed]
  • Steere AC, Malawista SE, Newman JH, Spieler PN, Bartenhagen NH. Antibiotic therapy in Lyme disease. Ann Intern Med. 1980;93:1–8. [PubMed]
  • Wormser GP. Clinical practice. Early Lyme disease. N Engl J Med. 2006;354:2794–2801.[PubMed]
  • Wormser GP, Ramanathan R, Nowakowski J, McKenna D, Holmgren D, Visintainer P, Dornbush R, Singh B, Nadelman RB. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:697–704. [PubMed]
  • Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, Wisniewski M, Collins JJ. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother. 1995;39:661–667.[PMC free article] [PubMed]
  • Massarotti EM, Luger SW, Rahn DW, Messner RP, Wong JB, Johnson RC, Steere AC. Treatment of early Lyme disease. Am J Med. 1992;92:396–403. [PubMed]
  • Luft BJ, Dattwyler RJ, Johnson RC, Luger SW, Bosler EM, Rahn DW, Masters EJ, Grunwaldt E, Gadgil SD. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial. Ann Intern Med. 1996;124:785–791. [PubMed]
  • Dinser R, Jendro MC, Schnarr S, Zeidler H. Antibiotic treatment of Lyme borreliosis: what is the evidence? Ann Rheum Dis. 2005;64:519–523. [PMC free article] [PubMed]
  • Dattwyler RJ, Luft BJ, Kunkel MJ, Finkel MF, Wormser GP, Rush TJ, Grunwaldt E, Agger WA, Franklin M, Oswald D, Cockey L, Maladorno D. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med. 1997;337:289–294. [PubMed]
  • Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics. 2002;109:1173–1177. [PubMed]
  • Arnez M, Pleterski-Rigler D, Luznik-Bufon T, Ruzic-Sabljic E, Strle F. Solitary erythema migrans in children: comparison of treatment with azithromycin and phenoxymethylpenicillin. Wien Klin Wochenschr. 2002;114:498–504. [PubMed]
  • Krause PJ, Telford SR, Spielman A, Sikand V, Ryan R, Christianson D, Burke G, Brassard P, Pollack R, Peck J, Persing DH. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996;275:1657–1660. [PubMed]
  • Hilton E, DeVoti J, Benach JL, Halluska ML, White DJ, Paxton H, Dumler JS. Seroprevalence and seroconversion for tick-borne diseases in a high-risk population in the northeast United States. Am J Med. 1999;106:404–409. [PubMed]
  • Swanson SJ, Neitzel D, Reed KD, Belongia EA. Coinfections acquired from ixodes ticks. Clin Microbiol Rev. 2006;19:708–727. [PMC free article] [PubMed]
  • Sood SK. What we have learned about Lyme borreliosis from studies in children. Wien Klin Wochenschr. 2006;118:638–642. [PubMed]
  • Halperin JJ. Diagnosis and treatment of the neuromuscular manifestations of lyme disease. Curr Treat Options Neurol. 2007;9:93–100. [PubMed]
  • Tveitnes D, Oymar K, Natas O. Laboratory data in children with Lyme neuroborreliosis, relation to clinical presentation and duration of symptoms. Scand J Infect Dis. 2009;41:355–362. [PubMed]
  • Tiemstra JD, Khatkhate N. Bell’s palsy: diagnosis and management. Am Fam Physician.2007;76:997–1002. [PubMed]
  • Wilke M, Eiffert H, Christen HJ, Hanefeld F. Primarily chronic and cerebrovascular course of Lyme neuroborreliosis: case reports and literature review. Arch Dis Child. 2000;83:67–71.[PMC free article] [PubMed]
  • Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med.1991;325:159–163. [PubMed]
  • Kannian P, Drouin EE, Glickstein L, Kwok WW, Nepom GT, Steere AC. Decline in the frequencies ofBorrelia burgdorferi OspA161 175-specific T cells after antibiotic therapy in HLA-DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory lyme arthritis. J Immunol.2007;179:6336–6342. [PubMed]
  • Dressler F, Girschick HJ, Huppertz HI, Lahdenne P. Pediatric Rheumatology European Society Clinical Guidelines: Lyme arthritis. Pediatr Rheumatol Online J. 2004;8:346–349.
  • Luft BJ, Bosler EM, Dattwyler RJ. Lyme borreliosis. Int J Antimicrobial Agents. 1994;3:251–258.[PubMed]
  • Bentas W, Karch H, Huppertz HI. Lyme arthritis in children and adolescents: outcome 12 months after initiation of antibiotic therapy. J Rheumatol. 2000;27:2025–2030. [PubMed]
  • Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323:1438–1444. [PubMed]
  • Lopez-Alberola RF. Neuroborreliosis and the pediatric population: a review. Rev Neurol.2006;42(Suppl 3):S91–S96. [PubMed]
  • Asbrink E, Hovmark A, Hederstedt B. The spirochetal etiology of acrodermatitis chronica atrophicans Herxheimer. Acta Derm Venereol. 1984;64:506–512. [PubMed]
  • Mullegger RR, Glatz M. Skin manifestations of lyme borreliosis: diagnosis and management. Am J Clin Dermatol. 2008;9:355–368. [PubMed]
  • Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Norton D, Levy L, Wall D, McCall J, Kosinski M, Weinstein A. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345:85–92. [PubMed]
  • Feder HM Jr, Johnson BJ, O’Connell S, Shapiro ED, Steere AC, Wormser GP. A critical appraisal of ‘chronic Lyme disease’. N Engl J Med. 2007;357:1422–1430. [PubMed]
  • Seidel MF, Domene AB, Vetter H. Differential diagnoses of suspected Lyme borreliosis or post-Lyme-disease syndrome. Eur J Clin Microbiol Infect Dis. 2007;26:611–617. [PubMed]
  • Baker PJ. Perspectives on ‘chronic Lyme disease’. Am J Med. 2008;121:562–564. [PubMed]
  • Holl-Wieden A, Suerbaum S, Girschick HJ. Seronegative Lyme arthritis. Rheumatol Int.2007;27:1091–1093. [PubMed]
  • Schutzer SE, Coyle PK, Reid P, Holland B. Borrelia burgdorferi-specific immune complexes in acute Lyme disease. JAMA. 1999;282:1942–1946. [PubMed]
  • Fawcett PT, Rose CD, Gibney KM, Doughty RA. Correlation of seroreactivity with response to antibiotics in pediatric Lyme borreliosis. Clin Diagn Lab Immunol. 1997;4:85–88. [PMC free article][PubMed]
  • Stricker RB, Lautin A, Burrascano JJ. Lyme disease: the quest for magic bullets. Chemotherapy.2006;52:53–59. [PubMed]
  • Hovius JW, van Dam AP, Fikrig E. Tick-host-pathogen interactions in Lyme borreliosis. Trends Parasitol. 2007;23:434–438. [PubMed]
  • Simon MM, Schaible UE, Wallich R, Kramer MD. A mouse model for Borrelia burgdorferi infection: approach to a vaccine against Lyme disease. Immunol Today. 1991;12:11–16. [PubMed]
  • Sikand VK, Halsey N, Krause PJ, Sood SK, Geller R, Van Hoecke C, Buscarino C, Parenti D. Safety and immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against lyme disease in healthy children and adolescents: a randomized controlled trial. Pediatrics.2001;108:123–128. [PubMed]
  • Telford SR, Fikrig E, Barthold SW, Brunet LR, Spielman A, Flavell RA. Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. J Exp Med.1993;178:755–758. [PMC free article] [PubMed]
  • de Silva AM, Telford SR, Brunet LR, Barthold SW, Fikrig E. Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. J Exp Med. 1996;183:271–275.[PMC free article] [PubMed]
  • Hsia EC, Chung JB, Schwartz JS, Albert DA. Cost-effectiveness analysis of the Lyme disease vaccine. Arthritis Rheum. 2002;46:1651–1660. [PubMed]

Articles from Arthritis Research & Therapy are provided here courtesy of BioMed Central