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Lyme disease: recognition of the chronic form, new protocol, a victory for the victims.
PROTOCOL.
Will the sick win their fight?
This fight for years against the health authorities and part of the medical community for everything related to the diagnosis, treatment and management of Lyme disease.
Indeed, these days, the almost definitive version of the national protocol of diagnosis and care (PNDS) must be validated by the High Authority of Health (HAS).
Developed since a little over a year by doctors and patient associations, it must define the management of Lyme disease caused by the bacterium Borrelia burgdorferi.
It will de facto replace the protocol of the 2006 consensus conference widely disputed by patients and some scientists.
At the center of the controversy: diagnostic tests.
In the consensus of 2006, the diagnosis could be made only from two serological tests, the famous Elisa and Western Blot.
Problem: for years, these tests are strongly criticized for their unreliability.
Many patients suffering from symptoms often very disabling but declared negative by serology are then in a therapeutic stalemate since they can not benefit from the courses of antibiotics prescribed to fight against the disease.
A clinical examination to make the diagnosis
TESTS. One of the first claims of patient associations was the removal of these tests.
The PNDS whose content will soon be made public, will be particularly scrutinized on this point.
But according to our information, the tests would not be removed from the protocol.
On the other hand, they would no longer be indispensable for the recognition of the disease.
It would now be the clinical examination that will allow the doctor to make the diagnosis of Lyme disease, even if the serology is negative.
The symptoms therefore outweigh the tests.
If this is confirmed, it is a disavowal for the National Reference Center (CNR) borreliosis (including Lyme disease is a part), led by Professor Benedict Jaulhac, unwavering support for the reliability of tests.
And therefore, a victory for the patient associations.
Another point of contention is the recognition of chronic disease, especially in patients who have benefited from antibiotic treatment, but whose symptoms persist.
The condition of these patients suggests that Borrelia, the bacterium responsible for the disease, can persist in the body. Even after antibiotic treatment.
A hypothesis still strongly contested by the CNR which considers that the treatment is still effective.
The new protocol currently being validated by the HAS may nevertheless be based on several recent scientific publications that seem to challenge the CNR's positions.
For example, in December, an article in Frontiers in Medicine, the leading journal, showed that Lyme disease could be reliably diagnosed by measuring symptoms in a clinical examination.
The researchers compared healthy people (control group) who had never been affected by the disease to patients with "Lyme disease post-treatment syndrome" or PTLDS.
The latter corresponds to people who have been diagnosed with Lyme and then treated conventionally with an antibiotic but still suffering from the symptoms of the disease.
The results of this study clearly indicate that, unlike healthy individuals, PTLDS patients still show the same symptoms:
severe fatigue, musculoskeletal pain, sleep disturbance and depression.
"The diagnosis of PTLDS is based on accurate documentation of the patient's history of treating Lyme disease.
It's a diagnosis of exclusion from other possible conditions with the same symptoms, "said John Aucott, lead author of the study and a specialist in Lyme disease at the Johns Hopkins University School of Medicine in Baltimore (USA). United).
CCL19.
Concerning the serological examinations, the researcher confirms their unreliability: "The Elisa and Western Blot tests can be negative during the observation of the PTLDS.
Some try to use them for the diagnosis of PTLDS, but they are not sensitive enough and specific. "
The team of John Aucott is also working on another track, the presence of a new potential biomarker, CCL19, a small protein that attracts certain cells of the immune system (T lymphocyte) to the site of inflammation (where unfolds the infection).
"If the level of CCL19 is still high after antibiotic treatment, it means that the immune system is still activated.
This activation may be due to the fact that there are antigens of the bacterium or intact bacteria, responsible for the inflammation, "explains John Aucott, who admits that these studies are still preliminary and that other biomarkers of the disease must to be analyzed.
The bacterium can survive antibiotic treatment
Still, the persistence of symptoms could be explained simply by the persistence of the bacteria in the body.
This is shown in two recent studies of rhesus macaque published in The American Journal of Pathology and Plos One.
The researchers experimentally infected the monkeys and then treated them with antibiotics as in humans.
Twelve to thirteen months after infection followed by treatment, they observe inflammation of various tissues (meninges, brain stem, anterior and posterior limb nerves, bladder, skeletal muscle, myocardium, etc.).
In other words, an immune response.
With the help of numerous analytical techniques, they have finally found in some tissues the bacteria in small quantities, but intact and always active.
Conclusion, not only can she survive the antibiotic treatment, but in addition it remains pathological.
At least, in rhesus macaque.
"But it's the best animal model to study Lyme disease," says Monica Embers, the researcher who led the research at Tulane University (USA).
It is the macaque that best mimics the multi-organ nature of the disease in humans.
Unlike other animal models, markers of the disease such as erythema migrans, heart disease, joints and central and peripheral nervous system are all observed.
In addition, the spread of the bacteria, its concentration in the tissues and the immune response to infection are very similar to what is observed in humans. "
To explain the persistence of the pathogen after antibiotic treatment, the researcher mentions her adaptability:
"Our hypothesis is that Borrelia has adapted to the host by escaping the recognition of the immune system and has entered a phase of slow growth, possibly dormancy, following antibiotic treatment.
It should be noted that we used doxycycline, the most used antibiotic in humans against Lyme disease.
However, this antibiotic does not kill the bacteria, but only stops its growth.
So that a slow-growing Borrelia can be tolerant to doxycycline and resume growth when it is no longer exposed to the antibiotic. "
Symptoms attributed in part to residual inflammation
Results from Monica Embers' team show that symptoms of chronic disease can be partly attributed to residual inflammation in and around tissues that harbor a small amount of host-adapted persistent bacteria.
With this work, it becomes increasingly difficult to deny the existence of a chronic disease even after treatment with antibiotics.
As for the tests, their unreliability is hardly any doubt.
Even Western Blot, which was considered to be more reliable than Elisa, is not immune to criticism:
"New and improved diagnostic tests are on the horizon and this is absolutely necessary. The Western Blot is an antiquated technique with possible subjective interpretations and reduced specificity.
It must be replaced by something more powerful, "concluded Monica Embers.
Will the sick win their fight?
This fight for years against the health authorities and part of the medical community for everything related to the diagnosis, treatment and management of Lyme disease.
Indeed, these days, the almost definitive version of the national protocol of diagnosis and care (PNDS) must be validated by the High Authority of Health (HAS).
Developed since a little over a year by doctors and patient associations, it must define the management of Lyme disease caused by the bacterium Borrelia burgdorferi.
It will de facto replace the protocol of the 2006 consensus conference widely disputed by patients and some scientists.
At the center of the controversy: diagnostic tests.
In the consensus of 2006, the diagnosis could be made only from two serological tests, the famous Elisa and Western Blot.
Problem: for years, these tests are strongly criticized for their unreliability.
Many patients suffering from symptoms often very disabling but declared negative by serology are then in a therapeutic stalemate since they can not benefit from the courses of antibiotics prescribed to fight against the disease.
A clinical examination to make the diagnosis
TESTS. One of the first claims of patient associations was the removal of these tests.
The PNDS whose content will soon be made public, will be particularly scrutinized on this point.
But according to our information, the tests would not be removed from the protocol.
On the other hand, they would no longer be indispensable for the recognition of the disease.
It would now be the clinical examination that will allow the doctor to make the diagnosis of Lyme disease, even if the serology is negative.
The symptoms therefore outweigh the tests.
If this is confirmed, it is a disavowal for the National Reference Center (CNR) borreliosis (including Lyme disease is a part), led by Professor Benedict Jaulhac, unwavering support for the reliability of tests.
And therefore, a victory for the patient associations.
Another point of contention is the recognition of chronic disease, especially in patients who have benefited from antibiotic treatment, but whose symptoms persist.
The condition of these patients suggests that Borrelia, the bacterium responsible for the disease, can persist in the body. Even after antibiotic treatment.
A hypothesis still strongly contested by the CNR which considers that the treatment is still effective.
The new protocol currently being validated by the HAS may nevertheless be based on several recent scientific publications that seem to challenge the CNR's positions.
For example, in December, an article in Frontiers in Medicine, the leading journal, showed that Lyme disease could be reliably diagnosed by measuring symptoms in a clinical examination.
The researchers compared healthy people (control group) who had never been affected by the disease to patients with "Lyme disease post-treatment syndrome" or PTLDS.
The latter corresponds to people who have been diagnosed with Lyme and then treated conventionally with an antibiotic but still suffering from the symptoms of the disease.
The results of this study clearly indicate that, unlike healthy individuals, PTLDS patients still show the same symptoms:
severe fatigue, musculoskeletal pain, sleep disturbance and depression.
"The diagnosis of PTLDS is based on accurate documentation of the patient's history of treating Lyme disease.
It's a diagnosis of exclusion from other possible conditions with the same symptoms, "said John Aucott, lead author of the study and a specialist in Lyme disease at the Johns Hopkins University School of Medicine in Baltimore (USA). United).
CCL19.
Concerning the serological examinations, the researcher confirms their unreliability: "The Elisa and Western Blot tests can be negative during the observation of the PTLDS.
Some try to use them for the diagnosis of PTLDS, but they are not sensitive enough and specific. "
The team of John Aucott is also working on another track, the presence of a new potential biomarker, CCL19, a small protein that attracts certain cells of the immune system (T lymphocyte) to the site of inflammation (where unfolds the infection).
"If the level of CCL19 is still high after antibiotic treatment, it means that the immune system is still activated.
This activation may be due to the fact that there are antigens of the bacterium or intact bacteria, responsible for the inflammation, "explains John Aucott, who admits that these studies are still preliminary and that other biomarkers of the disease must to be analyzed.
The bacterium can survive antibiotic treatment
Still, the persistence of symptoms could be explained simply by the persistence of the bacteria in the body.
This is shown in two recent studies of rhesus macaque published in The American Journal of Pathology and Plos One.
The researchers experimentally infected the monkeys and then treated them with antibiotics as in humans.
Twelve to thirteen months after infection followed by treatment, they observe inflammation of various tissues (meninges, brain stem, anterior and posterior limb nerves, bladder, skeletal muscle, myocardium, etc.).
In other words, an immune response.
With the help of numerous analytical techniques, they have finally found in some tissues the bacteria in small quantities, but intact and always active.
Conclusion, not only can she survive the antibiotic treatment, but in addition it remains pathological.
At least, in rhesus macaque.
"But it's the best animal model to study Lyme disease," says Monica Embers, the researcher who led the research at Tulane University (USA).
It is the macaque that best mimics the multi-organ nature of the disease in humans.
Unlike other animal models, markers of the disease such as erythema migrans, heart disease, joints and central and peripheral nervous system are all observed.
In addition, the spread of the bacteria, its concentration in the tissues and the immune response to infection are very similar to what is observed in humans. "
To explain the persistence of the pathogen after antibiotic treatment, the researcher mentions her adaptability:
"Our hypothesis is that Borrelia has adapted to the host by escaping the recognition of the immune system and has entered a phase of slow growth, possibly dormancy, following antibiotic treatment.
It should be noted that we used doxycycline, the most used antibiotic in humans against Lyme disease.
However, this antibiotic does not kill the bacteria, but only stops its growth.
So that a slow-growing Borrelia can be tolerant to doxycycline and resume growth when it is no longer exposed to the antibiotic. "
Symptoms attributed in part to residual inflammation
Results from Monica Embers' team show that symptoms of chronic disease can be partly attributed to residual inflammation in and around tissues that harbor a small amount of host-adapted persistent bacteria.
With this work, it becomes increasingly difficult to deny the existence of a chronic disease even after treatment with antibiotics.
As for the tests, their unreliability is hardly any doubt.
Even Western Blot, which was considered to be more reliable than Elisa, is not immune to criticism:
"New and improved diagnostic tests are on the horizon and this is absolutely necessary. The Western Blot is an antiquated technique with possible subjective interpretations and reduced specificity.
It must be replaced by something more powerful, "concluded Monica Embers.