The LYME disease, an approach to effective treatment.
La enfermedad de LYME, enfoque para un buen tratamiento.
===================
Hello friends of the DERMAGIC EXPRESS network today brings you a hot
topic:
LYME DISEASE, DEMENTIA, AND ALZHEIMER, AN APROACH FOR EFFECTIVE
TREATMENT.
The LYME DISEASE or ERIYTHEMA MIGRANS was first described in the year 1.975
in the United States in a town of Connecticut called
OLD LYME, which is close to the
Connecticut River, which ends in the strait of LONG ISLAND, ATLANTIC ocean ,
Hence his name.
This disease was confused for years with JUVENILE RHEUMATOID ARTHRITIS, due to the symptoms presented by the patients, until in 1.981 when WILLY BURGDORFER, discovered the bacterium that caused the disease, SPIROCHETA type, isolating it from the digestive tract of TICKS of the genus IXODES subtype RICINUS.
LYME disease is the most common pathology transmitted by vectors in the United States, and not only affects that locality of Connecticut, ALL THE NORTHERN HEMISPHERE is involved and over the years it has become a real PUBLIC HEALTH problem.
In the United States, BORRELIA BURGDORFERI and MAYONII, are involved, in Europe and Asia, the BORRELIA AFZELII AND GARNINII. In Europe there are between 65,000 and 100,000 reported cases of LYME DISEASE, with the most affected countries being Germany, Austria and Switzerland. The CDC (Center for the Control of Infectious Diseases) admits and believes that there are between 300,000 and half a million new cases every year.
It is important that you know that the tick must be attached between 36 and 48 hours to your skin for the transmission of the disease. The tick can transmit the disease at any stage of its development, LARVA, NIYMPHS and ADULT, being NIYMPHS the most dangerous because of their number and small size that makes them difficult to detect.
THE SYMPTOMS OF THE DISEASE ARE DESCRIBED IN 4 STAGES:
1.) STAGE I: (3-30 days after the bite):
=============================
A.) ERYTHEMA AROUND THE BIT (ERYTHEMA MIGRANS), OCCURS IN 50% OF THE CASES
B.) FLU SYMPTOMS: CHILLS, FEVER, INFLAMMATION OF LIMBS, ARTICULATIONS, LYMPHATIC GANGLIA, NAUSEA, FATIGUE.
2.) STAGE II: (days to weeks after the bite):
================================
A.) CHRONIC SKIN INFECTIONS, ESPECIALLY LOWER LIMBS.
B.) CHANGES IN THE MOOD STATE: ANXIETY, DEPRESSION.
C.) SLEEP AND CONSCIOUS DISORDERS.
D.) VIOLENT HEADACHES.
E.) INFLAMMATION OF JOINTS.
F.) FACIAL PARALYSIS WITH LOSS OF MUSCULAR TONE IN HEMI OR TOTAL FACE.
G.) INCREASED HEART FREQUENCY.
H.) DIZZINESS.
3.) STAGE III: (Months to years after the bite):
=================================
A.) CARDIAC ARRHYTHMIA.
B.) NEUROLOGICAL DISORDER (5% OF UNTREATED PATIENTS) CHARACTERIZED BY PAIN, WEAKNESS AND / OR PICAZON IN HANDS AND FEET.
C.) CHANGE OF SHORT TERM MEMORY.
D.) MUSCULAR DETERIORATION AND SEVERE EXHAUSTION.
E.) EYE AND EAR INFLAMMATION.
F.) HEART DISEASES.
G.) LYME ARTHRITIS (60% OF PATIENTS NOT TREATED).
4.) STAGE IV: (Chronic state):
=======================
A.) MUSCULAR AND ARTICULAR PAIN.
B.) NEUROLOGICAL AND CONSCIOUSNESS ABNORMALITIES (NEUROBORRELIOSIS)
C.) FATIGUE.
D.) CARDIAC ALTERATIONS.
E.) IN 10 TO 20% OF PATIENTS, SYMPTOMS CAN PERSIST FOR YEARS BY LEADING THE ORGANISM TO A GREAT DETERIORATION, WHICH IS SO CALLED THE BORRELIOSIS SYNDROME.
The diagnosis of the disease is made through laboratory tests, history of exposure to the tick bite and symptoms of the disease.
For the year 1.998 the FDA approved the LYMErix VACCIN to combat this disease, by the laboratory GlaxoSmithKline (GSK), which unfortunately was a failure, due to the great adverse effects caused, being withdrawn from the market in the year 2.002. Read the review LYME DISEASE, LOOKING FOR A VACCINE.
It is important that you know that this spirochete, called BORRELIA, attacks your body in 3 ways:
1.) ACTIVE FORM (SPIROCHETAS):
The bacterium once penetrated into the organism spreads in its natural form, in the form of a contoured spindle, penetrates cells and tissues.
2.) ROUND SHAPE (LATENT):
In this way the spirochetes "CONTRACT" and take a rounded form as a defense mechanism when environmental conditions are not favorable as an antibiotic therapy. In this way they can survive and attack later.
3.) BIOFILM (LATENT FORM -COMPLEX):
Biofilm is a kind of "NEST" composed of all forms of spirochetes, which adhere to the tissue surfaces by a substance similar to the "glue" made up of polysaccharides. Under this form the bacteria can survive attacks of antibiotics and immune system for years causing severe damage to the body.
As you can realize it is not a simple bacterium, it is a "SUPER" bacteria that with these mechanisms of attack and defense has "in check" a large sector of the population of the planet.
In addition to this I tell you that in recent years there has been a lot of talk about THE ASSOCIATION OF LYME DISEASE WITH ALZHEIMER'S DISEASE, some authors disqualify this, others support this theory, based on the fact that NEUROBORRELIOSIS accelerates the Formation of the AMYLOID plaques specific to AZLHEIMER's disease.
In fact, there are proven studies showing that infections with: HERPES SIMPLE virus type 1, PICORNAVIRUS, BORNA DISEASE virus (Bornaviridae), CHLAMYDIA PNEUMONIAE, HELYCOBACTER PYLORI, and SPIROCHETAS contribute to the pathophysiology of ALZHEIMER (AD) .
Before you talk about what you can do, to fight against this disease, I'll introduce you THE OTHER FACE OF THE COIN, as I did with ZIKA VIRUS, MICROCEFALIA AND TRANSGENIC MOSQUITOS (Read here)
1.) HIDING A REALITY:
====================
Insurrance companies are "denied" to accept the CHRONIC condition of LYME DISEASE, since they only pay for short treatments of the disease, in other words, they do not want the word "CHRONIC" to be named or exist because it would involve millionaire expenses to cover the treatments , The CDC (Center for the Control of Infectious Diseases) and IDSA (Society of Infectious Diseases of America) KNOW IT AND COVER UP.
2.) DIFFICULT DIAGNOSIS:
=======================
In view of the BORRELIA, is a "INTELLIGENT" bacteria which has found ways (BIOFILM) to evade the immune system, in many cases the serological diagnosis becomes difficult, so many doctors "AVOID" to deal with the LYME DISEASE, to avoid losing their licenses, claims to the " Failure "of an accurate diagnosis. For this they have implemented doctors in charge "ONLY FOR LYME DISEASE, however many have turned their backs on this.
3.) UNREPORTED TRANSMISSION MECHANISMS:
==========================================
As I told you, the CDC has reported between 300,000 and 1,000,000 cases of LYME DISEASE, 2 times more common than breast cancer, and 6 times more common than AIDS. Traditionally the disease is transmitted by ticks, but it is speculated that it can also be transmitted by MOSQUITOS, even talking about the possibility of transmission by SEXUAL RELATIONS, based on the fact that THE BORRELIA IS A SPIROCHETA like the SYPHILIS, that in its TERTIARY STATE attacks the brain producing DEMENTIA: NEUROSYPHILIS.
There are also studies in pets such as DOGS where BORRELIA was found in the URINE of infected animals, with the possibility of transmission to HUMANS through contact with it.
4.) BUSINESS BEHIND THE DISEASE:
==============================
It has been proven that the research panels on LYME DISEASE are involved in business with DIAGNOSTIC KIT, PATENTS, AND PAYMENTS BY INSURANCE COMPANIES, in other words, corruption behind a disease, to obtain dollars.
5.) THE UNKNOWN HISTORY OF LYME DISEASE: UNDER OUR SKIN (DOCUMENTARY):
========================================================================
Documentary of 100 min of duration realized in 2.008, that shows us the reality of the LYME DISEASE, A chilling story of microbes, medicine and money of which I leave this appointment:
"...Dr. Alan MacDonald, MD, who appears in the documentary 'Under Our Skin' (2008), says in the film that he found Borrelia's DNA (LYME) in 7 of 10 patients' brains. This makes a lot of sense, since syphilis, its cousin, also invades the brain TERTIARY stage or neurosyphilis. "Dr. Klinghardt, MD (also quoted from 'Under Our Skin') stated that" he never had a single one of his own, Patient with Alzheimer's, ALS, Parkinson's disease or multiple sclerosis who were negative for Borrelia .... "
6.) THE GREATER EPIDEMIC AFTER AIDS ?:
=====================================
Scientists and Doctors who have studied THE LYME DISEASE, and with the scientific evidence they have concluded that this disease has not been attacked properly which has transformed it IN A TRUE THREAT TO THE HEALTH OF THE WORLD POPULATION, and that there is much "dirty" Business behind all this.
WHAT TO DO TO FIGHT IT:
Like any investigator I will give you several data that can help you not to get the DISEASE and if you already have it:
1.) PROTECT YOUR SKIN FROM THE TICKS:
=====================================
A.) Wear long pants, thick shoes, double socks on your legs.
B.) Shave your legs to the knees, if there is no hair, it becomes more difficult for the tick to climb up your leg.
C.) Spread your skin (legs) with VASELINE or a moisturizing solution to which you will place 1 amp of B12 complex. The smell it emits repels the tick. First the vaseline, then the lotion. Vaseline protects your skin. The lotion repels by the smell.
D.) Use as a moisturizer after bath and nights a 10% UREA lotion. The smell repels the ticks.
2.) Make baits for mice containing DOXICYCLINE, at low doses (reference 21), when eating infected mice die spirochetes.
3.) IF YOU SUSPECT YOU ARE INFECTED:
====================================
Use a good antibiotic: the most recommended according to the studies are:
A.) DOXYCYCLINE.
B.) CEFUROXIME.
C.) CEFTRIAXONE.
D.) AMOXIXILINE.
E.) MINOCYCLINE.
F.) DAPSONE.
G.) TETRACYCLINES.
H.) TIGECYCLIN.
I.) SULFA.
OTHER MEDICINES: CIMETIDINE AND STATINS.
If you ask me which antibiotic I would use, I would tell you THE MINOCYCLE and why ?
1.) MINOCYCIN is an old antibiotic that has a HIGH BACTERICIDAL POWER against many BACTERIA, including MYCOBACTERIUM LEPRAE, here it reads LEPROSY 2.00O YEARS LATER where it has been demonstrated that this antibiotic is highly effective against this disease.
On the other hand TO THE MINOCYCLINE has been discovered its utility in ALZHEIMER'S DISEASE AS ANTI-INFLAMMATORY, as it crosses the blood-brain barrier, and if we join the "LOOSE CORDS" of which NEUROBORRELIOSIS is associated with ALZHEIMER, more reason justifies the use Of this antibiotic. Read here THE MINOCYCLINE, ALZHEIMER AND OTHER NEUROLOGICAL DISORDERS
DOSE: 100-200 MGRS EVERY 12 HOURS FOR 21 DAYS, Rest 1 week and REPEAT FOR THREE CYCLES.
2.) OFLOXACIN: this antibiotic is not on the list and I mention, why? Ofloxacin like minocycline is HIGHLY BACTERICID against MYCOBACTERIUM LEPRAE, CHLAMYDIA and others.
DOSAGE: 400 MGRS TWICE DAY FOR 21 DAYS.
COMBINED THERAPY: CEFTRIAXONE 2 Grs day intravenous for 14 days, plus MINOCYCLINE 200 mgrs day for 14 days
4.) NEUROPATHIC PAIN:
====================
I imagine you have tried all the NSAIDs (non-asteroid anti-inflammatory), I propose the PREGABALIN, and GABAPENTIN, the pregabalin is softer and derived from the GABAPENTIN, both highly effective in the POST HERPETIC PAIN, read here HERPES ZOSTER, NEURALGIA AND VACCINES.
DOSAGE OF PREGABALIN: 75-150-300 MGRS TWICE A DAY. These molecules have adverse effects of drowsiness, so you should take them with care. Pregabalin as a side effect acts as an antidepressant and neurostimulant. It helps you in three ways: PAIN, DEPRESSION AND ACTIVATION.
5.) FEVER:
=========
A.) WATER WARM BATHS FOR 20 MINUTES.
B.) COOL THE BODY WITH ANY MOISTURIZER.
C.) ANTIPYRETICS: There are many, I stay with ACETAMINOPHEN 650 MGRS EVERY 8 HOURS.
Undoubtedly do not stop consulting your doctor, to guide you well.
6.) IMPROVE PHYSICAL CONDITION:
================================
A.) WHEY PROTEIN, ANY BRAND, 3 GLASSES DAILY: BREAKFAST LUNCH AND DINNER.
Obviously ALL the antibiotics I mention are effective, and to combat the BIOFILM EFFECT, BO0RRELIA, is the possibility of treating the disease as LEPROSY with DAPSONE in the long term, plus other antibiotics for 6 months to 1 year. There are already studies on this. Read here LEPROSY IN CAPE WHITE there you will find the origin of DAPSONE and other antibiotics.
THIS IS THE GREAT ACHILLES' HEEL OF THE INSURANCE COMPANIES, long-term treatment equals BIG COSTS.
I close this, throwing this question in the air? SYPHILIS SPIROCHET "DIES" WITH BENZATINIC PENICILLIN, 2,400,000 IU, 1 single dose, preferably 3. (WITH ALUMINUM MONOESTERATE better).
Have our scientists thought of using it in LYME DISEASE ???? Which is also produced by A SPIROCHET.
To finish here, I leave you with 45 bibliographical references and illustrative photos, so that you know more about LYME DISEASE, and I wish the best to people suffering from this disease.
YOUR KEYS TO COMBAT LYME DISEASE MUST BE:
1.) A GOOD ANTIBIOTIC: MINOCYCLINE, OFLOXACIN, CEFTRIAXONE.
2.) A GOOD NEUROSTIMULANT AND ANALGESIC: PREGABALIN
3.) IMPROVE YOUR PHYSICAL CONDITION: WHEY PROTEIN.
4.) PROTEC YOUR BODY AND ENVIRONMENT ANGAINST THE TICK.
I am closing with this:
"... IF YOU WANT TO RIDE AGAINST BUROCRATS AND CLAIM YOUR RIGHTS, DO IT, BUT DO NOT STOP TREATING AND DO NOT GIVE UP ..."
Greetings to all.
Dr. Jose Lapenta.
This disease was confused for years with JUVENILE RHEUMATOID ARTHRITIS, due to the symptoms presented by the patients, until in 1.981 when WILLY BURGDORFER, discovered the bacterium that caused the disease, SPIROCHETA type, isolating it from the digestive tract of TICKS of the genus IXODES subtype RICINUS.
LYME disease is the most common pathology transmitted by vectors in the United States, and not only affects that locality of Connecticut, ALL THE NORTHERN HEMISPHERE is involved and over the years it has become a real PUBLIC HEALTH problem.
In the United States, BORRELIA BURGDORFERI and MAYONII, are involved, in Europe and Asia, the BORRELIA AFZELII AND GARNINII. In Europe there are between 65,000 and 100,000 reported cases of LYME DISEASE, with the most affected countries being Germany, Austria and Switzerland. The CDC (Center for the Control of Infectious Diseases) admits and believes that there are between 300,000 and half a million new cases every year.
It is important that you know that the tick must be attached between 36 and 48 hours to your skin for the transmission of the disease. The tick can transmit the disease at any stage of its development, LARVA, NIYMPHS and ADULT, being NIYMPHS the most dangerous because of their number and small size that makes them difficult to detect.
THE SYMPTOMS OF THE DISEASE ARE DESCRIBED IN 4 STAGES:
1.) STAGE I: (3-30 days after the bite):
=============================
A.) ERYTHEMA AROUND THE BIT (ERYTHEMA MIGRANS), OCCURS IN 50% OF THE CASES
B.) FLU SYMPTOMS: CHILLS, FEVER, INFLAMMATION OF LIMBS, ARTICULATIONS, LYMPHATIC GANGLIA, NAUSEA, FATIGUE.
2.) STAGE II: (days to weeks after the bite):
================================
A.) CHRONIC SKIN INFECTIONS, ESPECIALLY LOWER LIMBS.
B.) CHANGES IN THE MOOD STATE: ANXIETY, DEPRESSION.
C.) SLEEP AND CONSCIOUS DISORDERS.
D.) VIOLENT HEADACHES.
E.) INFLAMMATION OF JOINTS.
F.) FACIAL PARALYSIS WITH LOSS OF MUSCULAR TONE IN HEMI OR TOTAL FACE.
G.) INCREASED HEART FREQUENCY.
H.) DIZZINESS.
3.) STAGE III: (Months to years after the bite):
=================================
A.) CARDIAC ARRHYTHMIA.
B.) NEUROLOGICAL DISORDER (5% OF UNTREATED PATIENTS) CHARACTERIZED BY PAIN, WEAKNESS AND / OR PICAZON IN HANDS AND FEET.
C.) CHANGE OF SHORT TERM MEMORY.
D.) MUSCULAR DETERIORATION AND SEVERE EXHAUSTION.
E.) EYE AND EAR INFLAMMATION.
F.) HEART DISEASES.
G.) LYME ARTHRITIS (60% OF PATIENTS NOT TREATED).
4.) STAGE IV: (Chronic state):
=======================
A.) MUSCULAR AND ARTICULAR PAIN.
B.) NEUROLOGICAL AND CONSCIOUSNESS ABNORMALITIES (NEUROBORRELIOSIS)
C.) FATIGUE.
D.) CARDIAC ALTERATIONS.
E.) IN 10 TO 20% OF PATIENTS, SYMPTOMS CAN PERSIST FOR YEARS BY LEADING THE ORGANISM TO A GREAT DETERIORATION, WHICH IS SO CALLED THE BORRELIOSIS SYNDROME.
The diagnosis of the disease is made through laboratory tests, history of exposure to the tick bite and symptoms of the disease.
For the year 1.998 the FDA approved the LYMErix VACCIN to combat this disease, by the laboratory GlaxoSmithKline (GSK), which unfortunately was a failure, due to the great adverse effects caused, being withdrawn from the market in the year 2.002. Read the review LYME DISEASE, LOOKING FOR A VACCINE.
It is important that you know that this spirochete, called BORRELIA, attacks your body in 3 ways:
1.) ACTIVE FORM (SPIROCHETAS):
The bacterium once penetrated into the organism spreads in its natural form, in the form of a contoured spindle, penetrates cells and tissues.
2.) ROUND SHAPE (LATENT):
In this way the spirochetes "CONTRACT" and take a rounded form as a defense mechanism when environmental conditions are not favorable as an antibiotic therapy. In this way they can survive and attack later.
3.) BIOFILM (LATENT FORM -COMPLEX):
Biofilm is a kind of "NEST" composed of all forms of spirochetes, which adhere to the tissue surfaces by a substance similar to the "glue" made up of polysaccharides. Under this form the bacteria can survive attacks of antibiotics and immune system for years causing severe damage to the body.
As you can realize it is not a simple bacterium, it is a "SUPER" bacteria that with these mechanisms of attack and defense has "in check" a large sector of the population of the planet.
In addition to this I tell you that in recent years there has been a lot of talk about THE ASSOCIATION OF LYME DISEASE WITH ALZHEIMER'S DISEASE, some authors disqualify this, others support this theory, based on the fact that NEUROBORRELIOSIS accelerates the Formation of the AMYLOID plaques specific to AZLHEIMER's disease.
In fact, there are proven studies showing that infections with: HERPES SIMPLE virus type 1, PICORNAVIRUS, BORNA DISEASE virus (Bornaviridae), CHLAMYDIA PNEUMONIAE, HELYCOBACTER PYLORI, and SPIROCHETAS contribute to the pathophysiology of ALZHEIMER (AD) .
Before you talk about what you can do, to fight against this disease, I'll introduce you THE OTHER FACE OF THE COIN, as I did with ZIKA VIRUS, MICROCEFALIA AND TRANSGENIC MOSQUITOS (Read here)
1.) HIDING A REALITY:
====================
Insurrance companies are "denied" to accept the CHRONIC condition of LYME DISEASE, since they only pay for short treatments of the disease, in other words, they do not want the word "CHRONIC" to be named or exist because it would involve millionaire expenses to cover the treatments , The CDC (Center for the Control of Infectious Diseases) and IDSA (Society of Infectious Diseases of America) KNOW IT AND COVER UP.
2.) DIFFICULT DIAGNOSIS:
=======================
In view of the BORRELIA, is a "INTELLIGENT" bacteria which has found ways (BIOFILM) to evade the immune system, in many cases the serological diagnosis becomes difficult, so many doctors "AVOID" to deal with the LYME DISEASE, to avoid losing their licenses, claims to the " Failure "of an accurate diagnosis. For this they have implemented doctors in charge "ONLY FOR LYME DISEASE, however many have turned their backs on this.
3.) UNREPORTED TRANSMISSION MECHANISMS:
==========================================
As I told you, the CDC has reported between 300,000 and 1,000,000 cases of LYME DISEASE, 2 times more common than breast cancer, and 6 times more common than AIDS. Traditionally the disease is transmitted by ticks, but it is speculated that it can also be transmitted by MOSQUITOS, even talking about the possibility of transmission by SEXUAL RELATIONS, based on the fact that THE BORRELIA IS A SPIROCHETA like the SYPHILIS, that in its TERTIARY STATE attacks the brain producing DEMENTIA: NEUROSYPHILIS.
There are also studies in pets such as DOGS where BORRELIA was found in the URINE of infected animals, with the possibility of transmission to HUMANS through contact with it.
4.) BUSINESS BEHIND THE DISEASE:
==============================
It has been proven that the research panels on LYME DISEASE are involved in business with DIAGNOSTIC KIT, PATENTS, AND PAYMENTS BY INSURANCE COMPANIES, in other words, corruption behind a disease, to obtain dollars.
5.) THE UNKNOWN HISTORY OF LYME DISEASE: UNDER OUR SKIN (DOCUMENTARY):
========================================================================
Documentary of 100 min of duration realized in 2.008, that shows us the reality of the LYME DISEASE, A chilling story of microbes, medicine and money of which I leave this appointment:
"...Dr. Alan MacDonald, MD, who appears in the documentary 'Under Our Skin' (2008), says in the film that he found Borrelia's DNA (LYME) in 7 of 10 patients' brains. This makes a lot of sense, since syphilis, its cousin, also invades the brain TERTIARY stage or neurosyphilis. "Dr. Klinghardt, MD (also quoted from 'Under Our Skin') stated that" he never had a single one of his own, Patient with Alzheimer's, ALS, Parkinson's disease or multiple sclerosis who were negative for Borrelia .... "
6.) THE GREATER EPIDEMIC AFTER AIDS ?:
=====================================
Scientists and Doctors who have studied THE LYME DISEASE, and with the scientific evidence they have concluded that this disease has not been attacked properly which has transformed it IN A TRUE THREAT TO THE HEALTH OF THE WORLD POPULATION, and that there is much "dirty" Business behind all this.
WHAT TO DO TO FIGHT IT:
Like any investigator I will give you several data that can help you not to get the DISEASE and if you already have it:
1.) PROTECT YOUR SKIN FROM THE TICKS:
=====================================
A.) Wear long pants, thick shoes, double socks on your legs.
B.) Shave your legs to the knees, if there is no hair, it becomes more difficult for the tick to climb up your leg.
C.) Spread your skin (legs) with VASELINE or a moisturizing solution to which you will place 1 amp of B12 complex. The smell it emits repels the tick. First the vaseline, then the lotion. Vaseline protects your skin. The lotion repels by the smell.
D.) Use as a moisturizer after bath and nights a 10% UREA lotion. The smell repels the ticks.
2.) Make baits for mice containing DOXICYCLINE, at low doses (reference 21), when eating infected mice die spirochetes.
3.) IF YOU SUSPECT YOU ARE INFECTED:
====================================
Use a good antibiotic: the most recommended according to the studies are:
A.) DOXYCYCLINE.
B.) CEFUROXIME.
C.) CEFTRIAXONE.
D.) AMOXIXILINE.
E.) MINOCYCLINE.
F.) DAPSONE.
G.) TETRACYCLINES.
H.) TIGECYCLIN.
I.) SULFA.
OTHER MEDICINES: CIMETIDINE AND STATINS.
If you ask me which antibiotic I would use, I would tell you THE MINOCYCLE and why ?
1.) MINOCYCIN is an old antibiotic that has a HIGH BACTERICIDAL POWER against many BACTERIA, including MYCOBACTERIUM LEPRAE, here it reads LEPROSY 2.00O YEARS LATER where it has been demonstrated that this antibiotic is highly effective against this disease.
On the other hand TO THE MINOCYCLINE has been discovered its utility in ALZHEIMER'S DISEASE AS ANTI-INFLAMMATORY, as it crosses the blood-brain barrier, and if we join the "LOOSE CORDS" of which NEUROBORRELIOSIS is associated with ALZHEIMER, more reason justifies the use Of this antibiotic. Read here THE MINOCYCLINE, ALZHEIMER AND OTHER NEUROLOGICAL DISORDERS
DOSE: 100-200 MGRS EVERY 12 HOURS FOR 21 DAYS, Rest 1 week and REPEAT FOR THREE CYCLES.
2.) OFLOXACIN: this antibiotic is not on the list and I mention, why? Ofloxacin like minocycline is HIGHLY BACTERICID against MYCOBACTERIUM LEPRAE, CHLAMYDIA and others.
DOSAGE: 400 MGRS TWICE DAY FOR 21 DAYS.
COMBINED THERAPY: CEFTRIAXONE 2 Grs day intravenous for 14 days, plus MINOCYCLINE 200 mgrs day for 14 days
4.) NEUROPATHIC PAIN:
====================
I imagine you have tried all the NSAIDs (non-asteroid anti-inflammatory), I propose the PREGABALIN, and GABAPENTIN, the pregabalin is softer and derived from the GABAPENTIN, both highly effective in the POST HERPETIC PAIN, read here HERPES ZOSTER, NEURALGIA AND VACCINES.
DOSAGE OF PREGABALIN: 75-150-300 MGRS TWICE A DAY. These molecules have adverse effects of drowsiness, so you should take them with care. Pregabalin as a side effect acts as an antidepressant and neurostimulant. It helps you in three ways: PAIN, DEPRESSION AND ACTIVATION.
5.) FEVER:
=========
A.) WATER WARM BATHS FOR 20 MINUTES.
B.) COOL THE BODY WITH ANY MOISTURIZER.
C.) ANTIPYRETICS: There are many, I stay with ACETAMINOPHEN 650 MGRS EVERY 8 HOURS.
Undoubtedly do not stop consulting your doctor, to guide you well.
6.) IMPROVE PHYSICAL CONDITION:
================================
A.) WHEY PROTEIN, ANY BRAND, 3 GLASSES DAILY: BREAKFAST LUNCH AND DINNER.
Obviously ALL the antibiotics I mention are effective, and to combat the BIOFILM EFFECT, BO0RRELIA, is the possibility of treating the disease as LEPROSY with DAPSONE in the long term, plus other antibiotics for 6 months to 1 year. There are already studies on this. Read here LEPROSY IN CAPE WHITE there you will find the origin of DAPSONE and other antibiotics.
THIS IS THE GREAT ACHILLES' HEEL OF THE INSURANCE COMPANIES, long-term treatment equals BIG COSTS.
I close this, throwing this question in the air? SYPHILIS SPIROCHET "DIES" WITH BENZATINIC PENICILLIN, 2,400,000 IU, 1 single dose, preferably 3. (WITH ALUMINUM MONOESTERATE better).
Have our scientists thought of using it in LYME DISEASE ???? Which is also produced by A SPIROCHET.
To finish here, I leave you with 45 bibliographical references and illustrative photos, so that you know more about LYME DISEASE, and I wish the best to people suffering from this disease.
YOUR KEYS TO COMBAT LYME DISEASE MUST BE:
1.) A GOOD ANTIBIOTIC: MINOCYCLINE, OFLOXACIN, CEFTRIAXONE.
2.) A GOOD NEUROSTIMULANT AND ANALGESIC: PREGABALIN
3.) IMPROVE YOUR PHYSICAL CONDITION: WHEY PROTEIN.
4.) PROTEC YOUR BODY AND ENVIRONMENT ANGAINST THE TICK.
I am closing with this:
"... IF YOU WANT TO RIDE AGAINST BUROCRATS AND CLAIM YOUR RIGHTS, DO IT, BUT DO NOT STOP TREATING AND DO NOT GIVE UP ..."
Greetings to all.
Dr. Jose Lapenta.
EDITORIAL ESPAÑOL
==================
Hola amigos de la red DERMAGIC EXPRESS te trae hoy un tema bien caliente: ENFERMEDAD DE LYME, DEMENCIA Y ALZHEIMER, UN ENFOQUE PARA UN TRATAMIENTO EFICAZ. La ENFERMEDAD DE LYME o ERITEMA MIGRANS fue descrita por primera vez en el año de 1.975 en Los Estados Unidos en un Pueblo de Connecticut, denominado OLD LYME, que queda cercano al rio Connecticut, el cual desemboca en el estrecho de LONG ISLAND, océano ATLANTICO, de allí viene su nombre.
Esta enfermedad fue confundida por años con ARTRITIS REUMATOIDE JUVENIL, por los síntomas presentados por los pacientes, hasta que en año 1.981 WILLY BURGDORFER, descubrió la bacteria que ocasionaba la enfermedad, del tipo ESPIROQUETA, aislándola del tubo digestivo de la GARRAPATA del genero IXODES subtipo RICINUS.
La enfermedad de LYME es la patología más frecuente transmitida por vectores en Estados Unidos, y no solo afecta a esa localidad de Connecticut, TODO EL HEMISFERIO NORTE está involucrado y con los años se ha convertido en un real problema de SALUD PUBLICA.
En los estados Unidos la BORRELIA BURGDORFERI Y MAYONII, son las involucradas, en Europa y Asia, las BORRELIA AFZELII Y GARNINII. En Europa existen entre 65.000 y 100.000 casos reportados de ENFERMEDAD DE LYME, siendo los países más afectados Alemania, Austria y Suiza. El CDC (Centro Para el Control de Enfermedades infecciosas) admite y cree que hay entre 300.000 y medio millón de casos nuevos cada año.
Es importante que sepas que la garrapata debe estar adherida entre 36 y 48 horas a tu piel para que se produzca la transmisión de la enfermedad. La garrapata puede transmitir la enfermedad en cualquier etapa de su desarrollo, LARVA, NINFA Y ADULTO, siendo las NINFAS las más peligrosas por su número y pequeño tamaño que las hace difícil de detectar.
LOS SINTOMAS DE LA ENFERMEDAD SE DESCRIBEN EN 4 ETAPAS:
1.) ETAPA I: (3-30 días después de la picadura):
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A.) ERITEMA ALREDEDOR DE LA PICADURA (ERITEMA MIGRANS), OCURRE EN EL 50% DE LOS CASOS
B.) SINTOMAS DE GRIPE: ESCALOSFRIOS, FIEBRE, INFLAMACION DE ARTICULACIONES MIEMBROS, GANGLIOS LINFATICOS, NAUSEA, FATIGA.
2.) ETAPA II: (días a semanas después de la picadura):
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A.) INFECCIONES CRONICAS DE LA PIEL, ESPECIALMENTE MIEMBROS INFERIORES.
B.) CAMBIOS EN EL ESTADO ANIMICO: ANSIEDAD, DEPRESION.
C.) TRANSTORNOS DEL SUEÑO Y CONCIENCIA.
D.) VIOLENTOS DOLORES DE CABEZA.
E.) HINCHAZON DE LAS ARTICULACIONES.
F.) PARALISIS FACIAL CON PERDIDA DEL TONO MUSCULAR EN HEMICARA O TODA LA CARA.
G.) AUMENTO DE LA FRECUENCIA CARDIACA.
H.) MAREOS.
3.) ETAPA III: (Meses a años después de la picadura):
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A.) ARRITMIA CARDIACA.
B.) DESORDEN NEUROLOGICO (5% DE LOS PACIENTES NO TRATADOS) CARACTERIZADO POR DOLOR, DEBILIDAD Y / O PICAZON EN MANOS Y PIES.
C.) ALTERACION DE LA MEMORIA A CORTO PLAZO.
D.) DETERIORO MUSCULAR Y AGOTAMIENTO SEVERO.
E.) INFLAMACION DE OJOS Y OIDOS.
F.) AFECCIONES CARDIACAS.
G.) ARTRITIS DE LYME (60% DE LOS PACIENTES NO TRATADOS).
4.) ETAPA IV: (Estado crónico):
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A.) DOLORES MUSCULARES Y ARTICULARES.
B.) ANORMALIDADES NEUROLOGICAS Y DE LA CONCIENCIA (NEUROBORRELIOSIS).
C.) FATIGA.
D.) ALTERACIONES CARDIACAS.
E.) EN 10 A 20% DE LOS PACIENTES LOS SINTOMAS PUEDEN PERSISTIR POR AÑOS LLEVANDO AL ORGANISMO A UN GRAN DETERIORO, SIENDO ESTE DENOMINADO SINDROME DE BORRELIOSIS.
El diagnostico de la enfermedad se hace mediante exámenes de laboratorio, historia de exposición a la picadura de la garrapata y síntomas de la enfermedad.
Para el año 1.998 LA FDA (Administración de Alimentos y Medicinas) Aprobó la VACUNA LYMErix para combatir esta enfermedad, por el laboratorio GlaxoSmithKline (GSK), la cual lamentablemente fue un fracaso, debido a los grandes efectos adversos ocasionados, siendo retirada del mercado en él año 2.002. Lee acá la revisión BUSCANDO UNA VACUNA PARA LA ENFERMEDAD DE LYME.
Es importante que sepas que esta espiroqueta, llamada BORRELIA, ataca tu organismo de 3 formas:
1.) FORMA ACTIVA (ESPIROQUETAS):
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La bacteria una vez penetrado al organismo se disemina en su forma natural, en forma de huso contorneado, penetra células y tejidos.
2.) FORMA REDONDEADA (LATENTE):
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En esta forma las espiroquetas se 'CONTRAEN" y toman una forma redondeada, como mecanismo de defensa cuando las condiciones ambientales no son favorables como una terapia con antibióticos. De esta manera pueden sobrevivir y atacar posteriormente.
3.) BIOFILM (FORMA LATENTE -COMPLEJO):
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El biofilm es una especie de "NIDO" compuesto por todas las formas de espiroquetas, que se adhieren a las superficies de tejidos mediante una sustancia similar al "pegamento" compuesta por polisacáridos. Bajo esta forma las bacterias pueden sobrevivir a ataques de antibióticos y sistema inmune por años causando severos daños al organismo.
Como te podrás dar cuenta no se trata de una simple bacteria, es una "SUPER" bacteria que con estos mecanismos de ataque y defensa tiene en "jaque" a un gran sector de la población del planeta.
Además de ello te cuento que en los últimos años se ha estado hablando mucho de LA ASOCIACION de la ENFERMEDAD DE LYME con DEMENCIA Y ENFERMEDAD DE ALZHEIMER, algunos autores descalifican esto, otros apoyan esta teoría, basados en el hecho de que la NEUROBORRELIOSIS acelera la formación de las placas de AMILODE propias de la enfermedad de AZLHEIMER.
De hecho hay estudios comprobados donde se demuestra que infecciones por: HERPES SIMPLE virus tipo 1, PICORNAVIRUS, virus de la ENFERMEDAD DE BORNA (Bornaviridae), CHLAMYDIA PNEUMONIAE, HELYCOBACTER PYLORI, y ESPIROQUETAS contribuyen en la patofisiología de la enfermedad de ALZHEIMER (AD).
Antes de hablarte de lo que puedes hacer tu, para luchar contra esta enfermedad, te voy a presentar LA OTRA CARA DE LA MONEDA, como hice con EL ZIKA VIRUS , LA MICROCEFALIA Y LOS MOSQUITOS TRANSGENICOS (Lee aquí)
1.) OCULTANDO UNA REALIDAD:
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Las aseguradoras se "NIEGAN" a aceptar el estado CRONICO de la ENFERMEDAD DE LYME, pues solo pagan cortos tratamientos de la enfermedad, en otras palabras, no quieren que se nombre o exista la palabra "CRONICA" pues implicaría gastos millonarios en cubrir los tratamientos, el CDC (Centro para el Control de Enfermedades Infecciosas) e IDSA (Sociedad de Enfermedades Infecciosas de América) LO SABEN Y LO ENCUBREN.
2.) DIFICIL DIAGNOSTICO:
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En vista de que la BORRELIA, es una bacteria "INTELIGENTE". La cual ha encontrado formas (BIOFILM) de evadir el sistema inmune, en muchos casos el diagnostico serológico se hace difícil, por lo tanto muchos médicos "EVITAN" enfrentarse con la enfermedad DE LYME, para evitar perder sus licencias, por demandas ante el "fallo " de un diagnostico preciso. Para ello se han implementado médicos encargados "SOLO PARA ENFERMEDAD DE LYME, sin embargo muchos le han dado la espalda a esto.
3.) MECANISMOS DE TRANSMISION NO REPORTADOS:
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Como te dije, el CDC ha reportado entre 300.000 mil y 1.000.000 de casos de ENFERMEDAD DE LYME, 2 veces más común que el CANCER de mama, y 6 veces más común que el SIDA. Tradicionalmente la enfermedad es transmitida por garrapatas, pero se especula que también puede ser transmitida por MOSQUITOS, incluso se habla de la posibilidad de transmisión por RELACIONES SEXUALES, basados en el hecho de que LA BORRELIA ES UNA ESPIROQUETA como la SIFILIS, que en su estado TERCIARIO ataca el cerebro produciendo DEMENCIA: NEUROSIFILIS.
También hay estudios en mascotas como PERROS donde se encontró la BORRELIA en la ORINA de animales infectados, con la posibilidad de transmisión a HUMANOS a través del contacto con esta.
4.) EL NEGOCIO DETRAS DE LA ENFERMEDAD:
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Se ha comprobado que los paneles investigadores sobre la ENFERMEDAD DE LYME están involucrados en negocios con KIT DE DIAGNOSTICOS, PATENTES, Y PAGOS POR COMPAÑIAS ASEGURADORAS, en otras palabras la corrupción detrás de una enfermedad, para obtener dólares.
5.) LA HISTORIA NO CONTADA DE LA ENFERMEDAD DE LYME: BAJO NUESTRA PIEL (DOCUMENTAL):
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Documental de 100 min de duración realizado en 2.008, que nos muestra la realidad de la ENFERMEDAD DE LYME, Una historia escalofriante de microbios, medicina y dinero del cual te dejo esta cita:
".....El Dr. Alan MacDonald, MD, que aparece en el documental 'Under Our Skin' (2008), dice en la película que encontró el ADN de Borrelia (LYME) en 7 de los 10 cerebros de pacientes de Alzheimer post-mortem. Esto tiene mucho sentido, ya que la sífilis, su primo, también invade el cerebro en etapa TERCIARIA o neurosífilis. Dr. Klinghardt, MD (también citado de 'Under Our Skin') declaró que "nunca tuvo un solo paciente con Alzheimer, ALS, enfermedad de Parkinson o esclerosis múltiple que dieron negativo para Borrelia...."
6.) LA MAYOR EPIDEMIA DESPUES DEL SIDA ?:
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Científicos y Doctores que han estudiado LA ENFERMEDAD DE LYME, y con las pruebas científicas que tienen concluyen que ha esta enfermedad no se le ha atacado debidamente la cual la ha transformado EN UNA VERDADERA AMENAZA A LA SALUD DE LA POBLACION MUNDIAL, y que hay mucho negocio "sucio' detrás de todo esto.
QUE HACER PARA COMBATIRLA:
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Como todo investigador te voy a dar varios datos que pueden ayudarte a no contraer la ENFERMEDAD y si ya la tienes también:
1.) PROTEGE TU PIEL DE LAS PICADURAS:
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A.) Usa pantalones largos, calzado grueso, doble media en tus piernas.
B.) Afeita tus piernas hasta las rodillas, si no hay pelo, se le hace más difícil a la garrapata subir por tu pierna.
C.) Unta tu piel (piernas) con VASELINA o una solución hidratante a la cual le vas a colocar una ampolla de complejo B12. El olor que emite repele la garrapata. Primero la vaselina, luego la loción. La vaselina protege tu piel. La loción repele por el olor.
D.) Usa como hidratante después del baño y noches una loción de UREA al 10%. El olor repele las garrapatas.
2.) Haz cebos para ratones que contengan DOXICICLINA, A bajas dosis (referencia 21), al comerlos los ratones infectados mueren las espiroquetas.
3.) SI SOSPECHAS QUE ESTAS INFECTADO:
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Utiliza un buen antibiótico: los más recomendados según los estudios son:
A.) DOXIXICLINA.
B.) CEFUROXIMA.
C.) CEFTRIAXONA.
D.) AMOXIXILINA.
E.) MINOCICLINA.
F.) DAPSONA.
G.) TETRACICLINAS.
H.) TIGECICLINA.
I.) SULFA.
OTROS MEDICAMENTOS: CIMETIDINA Y ESTATINAS.
Si me preguntas cual antibiótico utilizaría yo, te diría LA MINOCICLINA y por que :
1.) LA MINOCICLINA es un viejo antibiótico que tiene un ALTO PODER BACTERICIDA contra muchas BACTERIAS, entre ellas el TEMIDO MYCOBACTERIUM LEPRAE, lee acá LA LEPRA 2.00O AÑOS DESPUES donde queda demostrado que este antibiótico es altamente efectivo contra esta enfermedad.
Por otra parte A LA MINOCICLINA SE le ha descubierto su utilidad en la ENFERMEDAD DE ALZHEIMER COMO ANTIINFLAMATORIO, pues atraviesa la barrera hematoencefalica, y si unimos los "CABOS SUELTOS" de que la NUEROBORRELIOSIS está asociada al ALZHEIMER, con más razón se justifica el uso de este antibiótico. Lee acá LA MINOCICLINA, ALZHEIMER Y OTROS DESORDENES NEUROLOGICOS
DOSIS: 100-200 MGRS CADA 12 HORAS POR 21 DIAS, Descansar 1 semana y REPETIR POR TRES CICLOS.
2.) OFLOXACINA: este antibiótico no está en la lista y te lo menciono por qué? La ofloxacina al igual que la minociclina es ALTAMENTE BACTERICIDA contra el MYCOBACTERIUM LEPRAE , CHLAMYDIA y otros.
DOSIS: 400 MGRS DOS VECES DIA POR 21 días.
TERAPIA COMBINADA: CEFTRIAXONA 2 Grs día intravenosos por 14 días, mas MINOCICLINA 200 mgrs día por 14 días
4.) DOLORES NEUROPATICOS:
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Me imagino que has ensayado todos los AINES (antiinflamatorios No asteroideos), yo te propongo la PREGABALINA, y GABAPENTIN , la pregabalina es más suave y derivada de la GABAPENTINA, ambas altamente efectivas en los dolores POST HERPETICOS, lee aquí HERPES ZOSTER, NEURALGIA Y VACUNAS.
DOSIS DE PREGABALINA: 75-150-300 MGRS DOS VECES DIA. Estas moléculas tienen efectos adversos de somnolencia, de modo que debes tomarlas con cuidado. La pregabalina como efecto secundario actúa como antidepresivo y neuro estimulante. Te ayuda de tres maneras: DOLOR, DEPRESION Y ACTIVACION.
5.) FIEBRE:
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A.) BAÑOS DE AGUA TIBIA POR 20 MINUTOS.
B.) FROTAR EL CUERPO CON CUALQUIER HIDRATANTE.
C.) ANTIPIRETICOS: Hay muchos, me quedo con ACETAMINOFEN 650 MGRS CADA 8 HORAS.
Indudablemente no dejes de consultar a tu medico, para que te oriente bien.
6.) MEJORAR CONDICI0N FISICA:
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A.) WHEY PROTEIN, CUALQUIER MARCA, 3 VASOS DIARIOS DESAYUNO ALMUERZO Y CENA.
Obviamente TODOS los antibióticos que te mencione son efectivos, y para combatir el EFECTO BIOFILM, de la BO0RRELIA, esta la posibilidad de tratar la enfermedad como la LEPRA con DPASONA a largo plazo, más otros antibióticos durante 6 meses a 1 año. Ya existen estudios al respecto. Lee acá LEPRA EN CABO BLANCO, allí encontraras el origen de la DAPSONA y otros antibióticos.
ESTE ES EL GRAN TALON DE AQUILES DE LAS ASEGURADORAS, tratamientos a largo plazo equivale a GRANDES COSTOS.
Cierro con esta pregunta al aire? LA ESPIROQUETA DE LA SIFILIS "MUERE" CON PENICILINA BENZATINICA, 2.400.000 UI, 1 sola dosis, preferiblemente 3. (CON MONOESTERATO DE ALUMINIO mejor).
Han pensado nuestros científicos en utilizarla en LA ENFERMEDAD DE LYME ???? La cual también es producida por UNA ESPIROQUETA.
Para finalizar aquí te dejo estas 45 referencias bibliográficas y fotos ilustrativas, para que conozcas más de lo que sabes sobre la ENFERMEDAD DE LYME, y les deseo lo mejor a las personas que padecen esta enfermedad.
TUS CLAVES PARA COMBATIR LA ENFERMEDAD DE LYME DEBERAN SER:
1.) UN BUEN ANTIBIOTICO: MINOCICLINA, OFLOXACINA, CEFTRIAXONA.
2.) UN BUEN NEUROESTIMULANTE Y ANALGESICO: PREGABALINA
3.) MEJORAR TU CONDICION FISICA: WHEY PROTEIN.
4.) PROTEGE TU CUERPO Y AMBIENTE CONTRA LA GARRAPATA.
Para terminar cierro con esto:
"...SI QUIERES MARCHAR CONTRA LOS BUROCRATAS Y RECLAMAR TUS DERECHOS, HAZLO, PERO NO DEJES DE HACERTE EL TRATAMIENTO Y NO TE RINDAS.... "
Saludos a Todos.
Dr. José Lapenta.
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REFRENCIAS BIBLIOGRAFICAS /
BIBLIOGRAPHICAL REFERENCES
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1.) Lyme neuroborreliosis and dementia.
2.) Can infections cause Alzheimer's disease?
3.) No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.
4.) Lyme neuroborreliosis and dementia.
5.) Cerebrovascular Events in Lyme Neuroborreliosis.
6.) Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a
multicentre, non-inferiority, double-blind, randomised trial.
7.) Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis and management.
8.) Lyme disease associated neuroretinitis - Case report.
9.) Neuroretinitis associated with serologies positive for bartonella henselae and borrelia burgdorferi.
10.) Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.
11.) Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717).
12.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
13.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
14.) Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi.
15.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
16.) In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China.
17.) Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial.
18,) The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic
Lyme Disease/Post Treatment Lyme Disease Syndrome
19.) Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.
20.) Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi.
21.) A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
22.) Comparison of the lifetime host-to-tick transmission between two strains of the Lyme disease pathogen Borrelia afzelii.
23.) Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review.
24.) Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector.
25.) Inefficient co-feeding transmission of Borrelia afzelii in two common European songbirds.
26.) Borrelia sp. phylogenetically different from Lyme disease- and relapsing fever-related Borrelia spp. in Amblyomma varanense from Python reticulatus.
27.) [Ixodes ricinus, transmitted diseases and reservoirs].
28.) ["Reversible" dementia in 2011].
29.) Chronic inflammation and amyloidogenesis in Alzheimer's disease -- role of Spirochetes.
30.) Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
31.) Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes.
32.) Alzheimer's disease--a spirochetosis?
33.) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
34.) Link between chronic bacterial inflammation and Alzheimer disease.
35.) Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?
36.) Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.
37.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
38.) Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.
39.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
40.) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?
41.) [Minocycline].
42.) Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis.
43.) Influence of tick and mammalian physiological temperatures on Borrelia burgdorferi biofilms.
44.) Cimetidine as a novel adjunctive treatment for early stage Lyme disease.
45.) Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas.
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1.) Lyme neuroborreliosis and dementia.
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J Alzheimers Dis. 2014;41(4):1087-93. doi: 10.3233/JAD-130446.
Blanc F1, Philippi N1, Cretin B1, Kleitz C2, Berly L2, Jung B1, Kremer S3, Namer IJ4, Sellal F5, Jaulhac B6, de Seze J7.
Author information
1
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
2
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
3
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Neuroradiology Service, Strasbourg, France.
4
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Nuclear Medicine Service, Strasbourg, France.
5
University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France General Hospital of Colmar, Neurology Service, Colmar, France.
6
University Hospital of Strasbourg, Laboratory of Bacteriology and National Center for Borrelia, Strasbourg, France.
7
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France INSERM U119, Strasbourg, France.
Abstract
INTRODUCTION:
Descriptions of Lyme disease and dementia are rare.
OBJECTIVE:
To describe patients with dementia and a positive "intrathecal anti-Borrelia antibody index" (AI), specific for neuroborreliosis.
METHODS:
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years.
RESULTS:
We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer's disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second.
CONCLUSION:
Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.
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2.) Can infections cause Alzheimer's disease?
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Epidemiol Rev. 2013;35:161-80. doi: 10.1093/epirev/mxs007. Epub 2013 Jan 24.
Mawanda F, Wallace R.
Abstract
Late-onset Alzheimer's disease (AD) is the most prevalent cause of dementia among older adults, yet more than a century of research has not determined why this disease develops. One prevailing hypothesis is that late-onset AD is caused by infectious pathogens, an idea widely studied in both humans and experimental animal models. This review examines the infectious AD etiology hypothesis and summarizes existing evidence associating infectious agents with AD in humans. The various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD are considered, as is the concordance between putative infectious agents and the epidemiology of AD. We searched the PubMed, Web of Science, and EBSCO databases for research articles pertaining to infections and AD and systematically reviewed the evidence linking specific infectious pathogens to AD. The evidence compiled from the literature linking AD to an infectious cause is inconclusive, but the amount of evidence suggestive of an association is too substantial to ignore. Epidemiologic, clinical, and basic science studies that could improve on current understanding of the associations between AD and infections and possibly uncover ways to control this highly prevalent and debilitating disease are suggested.
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3.) No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.
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Emerg Infect Dis. 2015 Nov;21(11):2036-9. doi: 10.3201/eid2111.150778.
Forrester JD, Kugeler KJ, Perea AE, Pastula DM, Mead PS.
Abstract
Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.
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4.) Lyme neuroborreliosis and dementia.
==========================================================
J Alzheimers Dis. 2014;41(4):1087-93. doi: 10.3233/JAD-130446.
Blanc F1, Philippi N1, Cretin B1, Kleitz C2, Berly L2, Jung B1, Kremer S3, Namer IJ4, Sellal F5, Jaulhac B6, de Seze J7.
Author information
1
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
2
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
3
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Neuroradiology Service, Strasbourg, France.
4
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Nuclear Medicine Service, Strasbourg, France.
5
University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France General Hospital of Colmar, Neurology Service, Colmar, France.
6
University Hospital of Strasbourg, Laboratory of Bacteriology and National Center for Borrelia, Strasbourg, France.
7
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France INSERM U119, Strasbourg, France.
Abstract
INTRODUCTION:
Descriptions of Lyme disease and dementia are rare.
OBJECTIVE:
To describe patients with dementia and a positive "intrathecal anti-Borrelia antibody index" (AI), specific for neuroborreliosis.
METHODS:
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years.
RESULTS:
We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer's disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second.
CONCLUSION:
Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.
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5.) Cerebrovascular Events in Lyme Neuroborreliosis.
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J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1671-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.056. Epub 2015 May 20.
Wittwer B1, Pelletier S2, Ducrocq X1, Maillard L1, Mione G1, Richard S3.
Author information
1
Stroke Unit, Department of Neurology, CHU Nancy, Hopital Central, Nancy Cedex, France.
2
Stroke Unit, CH Bar le Duc, Bar le Duc Cedex, France.
3
Stroke Unit, Department of Neurology, CHU Nancy, Hopital Central, Nancy Cedex, France. Electronic address: s.richard@chu-nancy.fr.
Abstract
BACKGROUND:
Cerebrovascular events in neuroborreliosis are a rare condition described only in isolated or small case series. No specific clinical or radiological features have been identified, and diagnosis is based on very different criteria.
METHODS:
We retrospectively describe cases diagnosed in the Stroke Unit of Nancy Hospital, located in the endemic area of the northeast of France. We also reviewed other cases found in the literature.
RESULTS:
We identified 5 cases in our center and 57 other reported cases. Mean age was 39 years (range 5 to 77). Possible previous contact with Borrelia burgdorferi (B burgdorferi) was found in about half of cases. Additional neurologic symptoms (headache, cognitive impairment, and/or gait disturbance) were found in 44% of cases. Cerebral imaging revealed both ischemic (87%) and hemorrhagic lesions (13%) with a multiterritorial aspect in 22% of strokes, and signs of vasculitis in 71%. Analysis of cerebrospinal fluid (CSF) revealed lymphocytic meningitis in 90% of cases and elevated protein level in 86%. CSF/serum anti-B burgdorferi antibody index (AI) was positive in 91% of cases. Outcome was favorable after appropriate antibiotic treatment. Our 5 patients presented a modified Rankin scale score 0-1, without any stroke recurrence, after a median follow-up of 2.8 years.
CONCLUSIONS:
The diagnosis of Lyme neuroborreliosis should be considered for patients with cerebrovascular events without obvious cause living in an endemic area, in the presence of repeat multiterritorial strokes at short intervals, other neurologic symptoms, a history of B burgdorferi infection, and radiological signs of vasculitis. Diagnosis can be confirmed by CSF analysis with AI but with an incomplete sensitivity.
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6.) Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a
multicentre, non-inferiority, double-blind, randomised trial.
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Lancet Neurol. 2008 Aug;7(8):690-5. doi: 10.1016/S1474-4422(08)70119-4. Epub 2008 Jun 21.
Ljøstad U1, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A.
Author information
1
Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway. unn.ljostad@sshf.no
Erratum in
Lancet Neurol. 2008 Aug;7(8):675.
Abstract
BACKGROUND:
Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis.
METHODS:
From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801.
FINDINGS:
Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events.
INTERPRETATION:
Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.
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7.) Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis and management.
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Indian J Ophthalmol. 2017 Mar;65(3):250-252. doi: 10.4103/ijo.IJO_151_17.
Guliani BP1, Kumar S1, Chawla N2, Mehta A1.
Author information
1
Department of Ophthalmology, VMMC and Safdarjung Hospital, New Delhi, India.
2
Department of Ophthalmology, Sanjay Gandhi Memorial Hospital, New Delhi, India.
Abstract
We present a case of neuroretinitis as presenting and the only presentation of Lyme disease in a 25-year-old female who visited hilly areas in the Himalayas of North India. She presented with right eye sudden and painless blurring of vision. Her vision at presentation was 20/60. She had fundus examination; fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) imaging showed classical features of neuroretinitis. No other organ was involved. Oral steroids were prescribed and relevant investigations sent for noninfective and infective causes. Worsened visual acuity (VA) to hand movement and positive IgM titers for Borrelia burgdorferi led to the diagnosis of Lyme disease-associated neuroretinitis. Treatment with oral doxycycline plus oral steroids for 4 weeks revealed VA of 20/20 and resolution of fundus and OCT changes. Neuroretinitis as presenting and the only presentation of Lyme disease will be discussed with serial fundus, FFA, and OCT pictures.
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8.) Lyme disease associated neuroretinitis - Case report.
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Acta Microbiol Immunol Hung. 2015 Dec;62(4):403-8. doi: 10.1556/030.62.2015.4.5.
Vanya M1, Fejes I2, Jako M1, Tula A3, Terhes G4, Janaky M2, Bartfai G1.
Author information
1
Department of Obstetrics and Gynaecology, Faculty of Medicine, Albert Szent-Gyorgyi Clinical Centre, University of Szeged , Szeged , Hungary.
2
Department of Ophthalmology, Faculty of General Medicine, Albert Szent-Gyorgyi Clinical Centre University of Szeged , Szeged , Hungary.
3
Department of Obstetrics and Gynaecology, Riga Stradiņš University , Riga , Latvia.
4
Department of Clinical Microbiology, Faculty of General Medicine, Albert Szent-Gyorgyi Clinical Centre, University of Szeged , Szeged , Hungary.
Abstract
We describe a rare case of Lyme disease complicated by unilateral neuroretinitis in the right eye. We report a case of a 27-year-old woman with blurred vision on her right eye. Because of the suspicion of optic neuritis (multiplex sclerosis) neurological examination was ordered. Surprisingly, computer tomography of the brain revealed incomplete empty sella, which generally results not monocular, but bilateral optic nerve swelling. Opthalmological examination (ophthalmoscopy and optical coherence tomography) indicated not only monocular optic nerve, but retinal oedema next to the temporal part of the right optic disk. Visual evoked potentials (VEP) demonstrated no P100 latency delay and mild differences between the amplitudes of the responses of the left and right eye. Optical coherence tomography (OCT) demonstrated the swelling of the optic nerve head and oedematous retina at the temporal part of the disk. Suspicion of an inflammatory cause of visual disturbance blood tests was ordered. Doxycycline treatment was ordered till the result of the blood test arrived. The Western blot and ELISA test were positive for Borrelia burgdorferi sensu lato. Following one week corticosteroide and ceftriaxone treatments, the patient displayed a clinical improvement. Unilateral neuroretinitis with optic disk swelling due to neuroborreliosis is a rare complication and in many cases it is difficult to distinguish between inflammatory and ischemic lesions. Further difficulty in the diagnosis can occur when intracranial alterations such as empty sella is demonstrated by CT examination.
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9.) Neuroretinitis associated with serologies positive for bartonella henselae and borrelia burgdorferi.
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Retin Cases Brief Rep. 2009 Summer;3(3):243-4. doi: 10.1097/ICB.0b013e31816bbec1.
Modjtahedi SP1, Truong SN, Gray AV, Morse LS.
Author information
1
From the Department of Ophthalmology & Vision Science, University of California at Davis Medical Center, Sacramento, California.
Abstract
PURPOSE:
To describe a patient with neuroretinitis with features of both cat-scratch disease and Lyme disease who had serologies positive for both Bartonella henselae and Borrelia burgdorferi.
METHODS:
Case report of a single individual undergoing diagnostic testing and treatment for neuroretinitis.
RESULTS:
A 47-year-old woman developed acute painless loss of vision and was found to have neuroretinitis. Diagnostic workup yielded serologies positive for both B. henselae and B. burgdorferi. The patient was treated with oral antibiotics for coverage of both etiologies, and her condition improved.
CONCLUSION:
Serologies positive for both B. henselae and B. burgdorferi can be obtained in the workup of neuroretinitis. Clinicians should be aware and use clinical judgment in guiding their diagnosis and treatment of neuroretinitis.
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10.) Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.
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BMC Nephrol. 2017 Feb 6;18(1):51. doi: 10.1186/s12882-017-0462-4.
Florens N1,2,3, Lemoine S4,5,6, Guebre-Egziabher F4,6, Valour F7, Kanitakis J8,9, Rabeyrin M9, Juillard L4,5,6.
Author information
1
Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, 69437, Lyon, Cedex 03, France. nans.florens@gmail.com.
2
Université Claude Bernard Lyon 1, Villeurbanne, France. nans.florens@gmail.com.
3
INSERM U1060, CarMeN, Université Claude Bernard Lyon 1, Lyon, France. nans.florens@gmail.com.
4
Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, 69437, Lyon, Cedex 03, France.
5
Université Claude Bernard Lyon 1, Villeurbanne, France.
6
INSERM U1060, CarMeN, Université Claude Bernard Lyon 1, Lyon, France.
7
Department of Infectious and Tropical Diseases, Hospices Civils de Lyon, Lyon, France.
8
Deparment of Dermatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
9
Department of Pathology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
Abstract
BACKGROUND:
There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis.
CASE PRESENTATION:
A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids.
CONCLUSION:
We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.
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11.) Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717).
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Int J Syst Evol Microbiol. 2017 Jan 27. doi: 10.1099/ijsem.0.001815. [Epub ahead of print]
Barbour AG1, Adeolu M2, Gupta RS3.
Author information
1
1Departments of Medicine, Microbiology & Molecular Genetics, and Ecology & Evolutionary Biology, University of California Irvine, Irvine, California, USA.
2
2Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
3
3McMaster University.
Abstract
This rebuttal Letter responds to a Letter in the IJSEM by Margos et al. challenging division of the genus Borrelia into two genera. We discuss here point-by-point the issues raised by Margos et al. and show that much of their criticism is unfounded and in several cases based on misreading of the presented results. We summarize here the extensive evidence based on genomic, genetic and phenotypic properties showing that the members of the family Borreliaceae (containing mainly the genus Borrelia) comprises two distinct and cohesive groups of microbes, differing in diseases they cause and other phenotypes. Prior to the proposed division, Borrelia spp. causing Lyme disease (LD) were already functionally treated as a distinct group, referred to as "B. burgdorferi sensu lato" to distinguish them from the other cluster of Borrelia spp. which includes all known species causing relapsing fever (RF). With the more explicit division of Borreliaceae species into two genus level groups, which are distinguishable from each other based on numerous unique genetic and molecular characteristics, the attention can now be focused on the biological significance of different molecular characteristics differentiating the two groups. The clear distinction of the LD and the RF groups of microbes based on numerous highly reliable markers, which are expected to be present even in uncharacterized members of these two groups, should aid in the improved diagnosis as well treatment of both these diseases, which is hindered by the conflation of a common name for agents causing two different types of diseases.
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12.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
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Antibiotics (Basel). 2017 Mar 22;6(1). pii: E10. doi: 10.3390/antibiotics6010010.
Feng J1, Zhang S2, Shi W3, Zhang Y4.
Author information
1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. jfeng16@jhu.edu.
2
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. szhang30@jhu.edu.
3
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. wshi3@jhu.edu.
4
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu.
Abstract
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug-containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
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13.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
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J Infect Dis. 2009 May 1;199(9):1379-88. doi: 10.1086/597807.
Bernardino AL1, Kaushal D, Philipp MT.
Author information
1
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
Abstract
Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP-1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated. Functionally, phosphorylation of IkappaBalpha and binding of NF-kappaB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.
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14.) Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi.
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Ticks Tick Borne Dis. 2010 Mar;1(1):30-4. doi: 10.1016/j.ttbdis.2009.11.004. Epub 2010 Jan 7.
Ates L1, Hanssen-Hübner C, Norris DE, Richter D, Kraiczy P, Hunfeld KP.
Author information
1
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt/Main, Germany.
Abstract
Tigecycline is a new glycylcycline that has recently been revealed to be very effective in vitro against a variety of Gram-negative and Gram-positive bacteria including multi-drug resistant microorganisms. Using a standardized microdilution susceptibility testing method, we determined the minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) of tigecycline, in parallel with doxycycline, tetracycline, and other antibiotic agents relevant for Lyme borreliosis treatment such as ceftriaxone and cefotaxime. The activity of all agents against 16 different Borrelia isolates belonging to all borrelial genospecies known to be pathogenic for humans was investigated and analyzed under standardized conditions. The overall rank order of MIC(90)s was tigecycline (≤0.016 mg/L) > ceftriaxone (0.03 mg/L) > cefotaxime (≤0.125 mg/L) > doxycycline (0.25 mg/L) > tetracycline (0.25 mg/L). The rank order of MBC(90)s was tigecycline (0.5 mg/L) > ceftriaxone (2 mg/L) > tetracycline (16 mg/L) > doxycycline (16 mg/L) > cefotaxime (>16 mg/L). High in vitro activity of the new glycylcycline against Borrelia was further substantiated by time-kill experiments performed with B. afzelii isolate EB1. Parallel testing of tigecycline and ceftriaxone demonstrated a bacteriostatic effect for 0.016 mg/L of tigecycline and for 0.03 mg/L for ceftriaxone after 72 h of incubation. Moreover, tigecycline was bactericidal at a concentration of 0.25 mg/L showing a >3 log(10) unit reduction of the initial inoculum, whereas for ceftriaxone a concentration of 2 mg/L was needed.
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15.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
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Barthold SW1, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.
Author information
1
Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. swbarthold@ucdavis.edu
Abstract
The effectiveness of a new first-in-class antibiotic, tigecycline (glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of tigecycline, saline (negative-effect controls), or a previously published regimen of ceftriaxone (positive-effect controls). Infection status was assessed at 3 months after treatment by culture, quantitative ospA real-time PCR, and subcutaneous transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with antibiotics were ospA PCR positive, although the DNA marker load was markedly decreased compared to that in saline-treated mice. Antibiotic treatment during the early stage of infection appeared to be more effective than treatment that began during later stages of infection. The viability of noncultivable spirochetes in antibiotic-treated mice (demonstrable by PCR) was confirmed by transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from antibiotic-treated mice revealed RNA transcription of several B. burgdorferi genes. These results extended previous studies with ceftriaxone, indicating that antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.
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16.) In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China.
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J Infect Chemother. 2000 Mar;6(1):65-7.
Li M1, Masuzawa T, Wang J, Kawabata M, Yanagihara Y.
Author information
1
International Center for Medical Research, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan. muqingl@kobe-u.ac.jp
Abstract
The antibiotic susceptibilities of seven Borrelia burgdorferi sensu lato isolates from Ixodes persulcatus in China were examined by in-vitro microdilution minimum inhibition concentration (MIC) and macrodilution minimum bactericidal concentration (MBC) methods. All isolates tested were susceptible to amoxicillin, erythromycin, and minocycline. The MICs of these drugs for the Chinese isolates were 0.025-0.1 microg/ml, <0.012-0.05 microg/ml, and <0.012-0.05 microg/ml, respectively. The MBCs were 0.1-0.39 microg/ml, <0.012-0.2 microg/ml, and 0.025-0.39 microg/ml, respectively. The in-vivo antimicrobial susceptibilities of the Chinese Borrelia isolates to two test drugs, amoxicillin and minocycline, were evaluated using ddY mice. Mice were infected by subcutaneous inoculation into the right hind footpad. When infection was confirmed, the mice were treated by subcutaneous injection of the test drugs into the back. Amoxicillin and minocycline, which possessed high in-vitro activities against Lyme disease Borrelia, provided good protection against borreliosis in this animal model. Higher doses of these drugs resulted in elimination of the Lyme disease spirochete from all animals receiving this course of treatment. The 50% curative doses (CD50) of amoxicillin and minocycline were 8.7 mg/kg and 3.1 mg/kg, respectively. This suggested that amoxicillin and minocycline could be useful for the treatment of Chinese Borrelia infection.
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17.) Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial.
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BMC Infect Dis. 2016 Feb 4;16:67. doi: 10.1186/s12879-016-1385-6.
Kumar R1, Basu A2, Sinha S3, Das M4, Tripathi P5, Jain A6, Kumar C7, Atam V8, Khan S9, Singh AS10.
Author information
1
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. rashmik2005@gmail.com.
2
National Brain Research Centre, Manesar, Haryana, 122051, India. anirban@nbrc.ac.in.
3
National Brain Research Centre, Manesar, Haryana, 122051, India. subrata.sinha@nbrc.ac.in.
4
INCLEN Trust International, Okhla Industrial Area, Phase-1, New Delhi, 110020, India. manoj@inclentrust.org.
5
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. piyush.tripathi@gmail.com.
6
Departments of Microbiology, King George's Medical University, Lucknow, UP, 226003, India. amita602002@yahoo.com.
7
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. dr_chandrakanta@yahoo.co.in.
8
Departments of Medicine, King George's Medical University, Lucknow, UP, 226003, India. v_atam@yahoo.com.
9
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. saima.firdaus@gmail.com.
10
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. amitkgmumedicine@gmail.com.
Abstract
BACKGROUND:
Acute encephalitis syndrome (AES) is a public health problem in India. Neuroinfections are believed to be the most important etiology. Minocycline is a semisythetic tetracycline having excellent penetration into cerebrospinal fluid, established neuroprotective and antiviral properties besides action on nonviral causes of AES. It has been shown to be effective in animal model of Japanese encephalitis (JE). A randomized, controlled trial of nasogastric/oral minocycline in JE and AES at a single centre in Uttar Pradesh, northern India, was therefore conducted.
METHODS:
Patients beyond 3 years of age - but excluding women aged 16-44 years - hospitalized with AES of < =7 days duration were enrolled and block randomized to receive nasogastric/oral minocycline or placebo suspension and followed up. Patients, study personnel and those entering data were blinded as to drug or placebo received. Primary outcome was cumulative mortality at 3 months from hospitalization. Analysis was by intention to treat.
RESULTS:
281 patients were enrolled, 140 received drug and 141 placebo. While there was no overall statistically significant difference in 3 month mortality between drug and placebo groups [RR = 0 · 83 (0 · 6-1 · 1)], there were encouraging trends in patients older than 12 years [RR = 0.70 (0.41-1.18)] and in Glasgow Outcome Score (GOS) at 3 months (χ(2) = 7 · 44, p = 0 · 059). These trends were further accentuated if patients dying within one day of reaching hospital were excluded [OR for 3 month mortality =0 · 70 (0 · 46-1 · 07), p = 0.090; 3 month GOS p = 0 · 028].
CONCLUSIONS:
A trend towards better outcomes was observed with minocycline, especially in those patients who survived the initial day in hospital. These findings should form the basis for planning a larger study and possibly including minocycline in the initial management of AES as seen here.
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18,) The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic
Lyme Disease/Post Treatment Lyme Disease Syndrome
=========================================================
Richard I Horowitz, MD and Phyllis Freeman, PhD
Hudson Valley Healing Arts Center, New York, USA
Corresponding author:
Richard I Horowitz, M.D. Medical Director, Hudson Valley Healing Arts Center, 4232 Albany Post Road, Hyde Park, New York 12538, USA, TTel:845-229-8977; Fax: 845-229-8930; E-mail: medical@hvhac.com
Abstract
Dapsone (diaminodiphenyl sulfone, i.e., DDS) is commonly used to treat dermatological conditions including acne, dermatitis herpetiformis, and leprosy. Mycobacterium leprae, a known "persister" bacteria, requires long-term treatment with intracellular medications including rifampin and Dapsone. Other "persister" bacteria recently have been identified, including Borrelia burgdorferi the agent of Lyme disease.
Objectives:
We tested the efficacy of DDS in patients with chronic Lyme disease/PTLDS with tick-borne co-infections including Babesiosis, who failed commonly used antibiotic and antimalarial protocols.
Methods:
100 patients with Lyme disease, 56 of who were Babesia positive, were placed on Dapsone and folic acid in combination with either one or two other intracellular drugs, including rifampin, tetracyclines, and/or macrolide antibiotics. Several patients also took cephalosporins, and all patients were on protocols to treat cystic forms of Borrelia and biofilms.
Results:
Patients completed a symptom severity survey before beginning treatment with Dapsone and then again after at least one month of treatment scoring their complaints from 0 indicating “none” to 4 indicating “severe” for symptoms including fatigue, joint and/or muscle pain, disturbed sleep, and cognitive difficulties. Results demonstrated that Dapsone significantly improved all patients’ clinical symptoms except for headache, where changes did not reach statistical significance. In addition, Dapsone, known to have anti-malarial effects, helped resistant Babesia symptoms of sweats, chills, and flushing. Lyme positive, Babesia positive patients also demonstrated significant changes in pain, disturbed sleep, and cognitive difficulties. Side effects included macrocytic anemia and rare cases of methemoglobinemia, which resolved by either decreasing the dose of Dapsone or increasing folic acid.
Conclusion:
Dapsone is a novel and effective “persister” drug for those with PTLDS and associated tick-borne co-infections who have failed classical antibiotic protocols. Further prospective trials must determine the DDS dose, length of treatment and best combination antibiotic therapy in order to effect a long-term health benefit.
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19.) Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.
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Microbes Infect. 2016 Jun;18(6):430-5. doi: 10.1016/j.micinf.2016.03.004. Epub 2016 Mar 16.
Van Laar TA1, Hole C1, Rajasekhar Karna SL1, Miller CL1, Reddick R2, Wormley FL1, Seshu J3.
Author information
1
South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
2
The Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, USA.
3
South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA. Electronic address: j.seshu@utsa.edu.
Abstract
Lyme disease (LD) is a systemic disorder caused by Borrelia burgdorferi. Lyme spirochetes encode for a functional 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR EC 1.1.1.88) serving as a rate limiting enzyme of the mevalonate pathway that contribute to components critical for cell wall biogenesis. Statins have been shown to inhibit B. burgdorferi in vitro. Using a mouse model of Lyme disease, we found that statins contribute to reducing bacterial burden and altering the murine immune response to favor clearance of spirochetes.
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20.) Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi.
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PLoS One. 2012;7(5):e38171. doi: 10.1371/journal.pone.0038171. Epub 2012 May 31.
Van Laar TA1, Lin YH, Miller CL, Karna SL, Chambers JP, Seshu J.
Author information
1
Department of Biology, Center for Excellence in Infection Genomics and The University of Texas at San Antonio, San Antonio, Texas, United States of America.
Abstract
Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a K(m) value of 132 µM with a V(max) of 1.94 µmol NADPH oxidized minute(-1) (mg protein)(-1) and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrA(Bb) and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease.
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21.) A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
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Am J Trop Med Hyg. 2008 May;78(5):803-5.
Dolan MC1, Zeidner NS, Gabitzsch E, Dietrich G, Borchert JN, Poché RM, Piesman J.
Author information
1
Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, Colorado 80521, USA. mcd4@cdc.gov
Abstract
The prophylactic and curative potential of doxycycline hyclate formulated in a rodent bait at concentrations of 250 and 500 mg/Kg was evaluated in a murine model of Lyme borreliosis. Both bait formulations prevented tick-transmitted Borrelia burgdorferi infection in 100% of C3H/HeJ mice (N = 16), as well as cured acute, established infection in mice (N = 8) exposed to bait for 14 days. Spirochete infection was cleared in 88.9% to 100% of infected nymphs feeding on mice fed 250 and 500 mg/Kg antibiotic bait formulations, respectively. These data provide evidence for exploring alternative techniques to prevent transmission of Lyme disease spirochetes.
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22.) Comparison of the lifetime host-to-tick transmission between two strains of the Lyme disease pathogen Borrelia afzelii.
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Parasit Vectors. 2016 Dec 16;9(1):645.
Jacquet M1, Margos G2,3, Fingerle V2,3, Voordouw MJ4.
Author information
1
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
2
National Reference Centre for Borrelia, Munich, Oberschleissheim, Germany.
3
Bavarian Health and Food Safety Authority, Munich, Oberschleissheim, Germany.
4
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland. maarten.voordouw@unine.ch.
Abstract
BACKGROUND:
Transmission from the vertebrate host to the arthropod vector is a critical step in the life-cycle of any vector-borne pathogen. How the probability of host-to-vector transmission changes over the duration of the infection is an important predictor of pathogen fitness. The Lyme disease pathogen Borrelia afzelii is transmitted by Ixodes ricinus ticks and establishes a chronic infection inside rodent reservoir hosts. The present study compares the temporal pattern of host-to-tick transmission between two strains of B. afzelii.
METHODS:
Laboratory mice were experimentally infected via tick bite with one of two strains of B. afzelii: A3 and A10. Mice were repeatedly infested with pathogen-free larval Ixodes ricinus ticks over a period of 4 months. Engorged larval ticks moulted into nymphal ticks that were tested for infection with B. afzelii using qPCR. The proportion of infected nymphs was used to characterize the pattern of host-to-tick transmission over time.
RESULTS:
Both strains of B. afzelii followed a similar pattern of host-to-tick transmission. Transmission decreased from the acute to the chronic phase of the infection by 16.1 and 29.3% for strains A3 and A10, respectively. Comparison between strains found no evidence of a trade-off in transmission between the acute and chronic phase of infection. Strain A10 had higher lifetime fitness and established a consistently higher spirochete load in nymphal ticks than strain A3.
CONCLUSION:
Quantifying the relationship between host-to-vector transmission and the age of infection in the host is critical for estimating the lifetime fitness of vector-borne pathogens.
KEYWORDS:
Borrelia afzelii; Co-feeding transmission; Ixodes ricinus; Life-history strategy; Lyme borreliosis; Spirochete; Systemic transmission; Tick-borne pathogen; Vector-borne pathogen
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23.) Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review.
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Parasit Vectors. 2015 Dec 18;8:643. doi: 10.1186/s13071-015-1257-8.
van Duijvendijk G1, Sprong H2, Takken W3.
Author information
1
Laboratory of Entomology, Wageningen University and Research Centre, Wageningen, The Netherlands. gilian.vanduijvendijk@wur.nl.
2
Laboratory for Zoonosis and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands. hein.sprong@rivm.nl.
3
Laboratory of Entomology, Wageningen University and Research Centre, Wageningen, The Netherlands. willem.takken@wur.nl.
Abstract
The tick Ixodes ricinus is the main vector of the spirochaete Borrelia burgdorferi sensu lato, the causal agent of Lyme borreliosis, in the western Palearctic. Rodents are the reservoir host of B. afzelii, which can be transmitted to I. ricinus larvae during a blood meal. The infected engorged larvae moult into infected nymphs, which can transmit the spirochaetes to rodents and humans. Interestingly, even though only about 1% of the larvae develop into a borreliae-infected nymph, the enzootic borreliae lifecycle can persist. The development from larva to infected nymph is a key aspect in this lifecycle, influencing the density of infected nymphs and thereby Lyme borreliosis risk. The density of infected nymphs varies temporally and geographically and is influenced by multi-trophic (tick-host-borreliae) interactions. For example, blood feeding success of ticks and spirochaete transmission success differ between rodent species and host-finding success appears to be affected by a B. afzelii infection in both the rodent and the tick. In this paper, we review the major interactions between I. ricinus, rodents and B. afzelii that influence this development, with the aim to elucidate the critical factors that determine the epidemiological risk of Lyme borreliosis. The effects of the tick, rodent and B. afzelii on larval host finding, larval blood feeding, spirochaete transmission from rodent to larva and development from larva to nymph are discussed. Nymphal host finding, nymphal blood feeding and spirochaete transmission from nymph to rodent are the final steps to complete the enzootic B. afzelii lifecycle and are included in the review. It is concluded that rodent density, rodent infection prevalence, and tick burden are the major factors affecting the development from larva to infected nymph and that these interact with each other. We suggest that the B. afzelii lifecycle is dependent on the aggregation of ticks among rodents, which is manipulated by the pathogen itself. Better understanding of the processes involved in the development and aggregation of ticks results in more precise estimates of the density of infected nymphs, and hence predictions of Lyme borreliosis risk.
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24.) Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector.
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Appl Environ Microbiol. 2017 Jan 17;83(3). pii: e02552-16. doi: 10.1128/AEM.02552-16. Print 2017 Feb 1.
Durand J1, Herrmann C2, Genné D3, Sarr A3, Gern L2, Voordouw MJ3.
Author information
1
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland jonas.durand@unine.ch.
2
Laboratory of Eco-Epidemiology of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
3
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
Abstract
Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens. Previous studies have mainly focused on interactions between pathogen strains in the vertebrate host, but little is known about what happens in the arthropod vector. Borrelia afzelii and Borrelia garinii are two species of spirochete bacteria that cause Lyme borreliosis in Europe and that share a tick vector, Ixodes ricinus Each of these two tick-borne pathogens consists of multiple strains that are often differentiated using the highly polymorphic ospC gene. For each Borrelia species, we studied the frequencies and abundances of the ospC strains in a wild population of I. ricinus ticks that had been sampled from the same field site over a period of 3 years. We used quantitative PCR (qPCR) and 454 sequencing to estimate the spirochete load and the strain diversity within each tick. For B. afzelii, there was a negative relationship between the two most common ospC strains, suggesting the presence of competitive interactions in the vertebrate host and possibly the tick vector. The flat relationship between total spirochete abundance and strain richness in the nymphal tick indicates that the mean abundance per strain decreases as the number of strains in the tick increases. Strains with the highest spirochete load in the nymphal tick were the most common strains in the tick population. The spirochete abundance in the nymphal tick appears to be an important life history trait that explains why some strains are more common than others in nature.
IMPORTANCE:
Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere and is caused by spirochete bacteria that belong to the Borrelia burgdorferi sensu lato species complex. These tick-borne pathogens are transmitted among vertebrate hosts by hard ticks of the genus Ixodes Each Borrelia species can be further subdivided into genetically distinct strains. Multiple-strain infections are common in both the vertebrate host and the tick vector and can result in competitive interactions. To date, few studies on multiple-strain vector-borne pathogens have investigated patterns of cooccurrence and abundance in the arthropod vector. We demonstrate that the abundance of a given strain in the tick vector is negatively affected by the presence of coinfecting strains. In addition, our study suggests that the spirochete abundance in the tick is an important life history trait that can explain why some strains are more common in nature than others.
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25.) Inefficient co-feeding transmission of Borrelia afzelii in two common European songbirds.
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Sci Rep. 2017 Jan 5;7:39596. doi: 10.1038/srep39596.
Heylen DJ1, Sprong H2, Krawczyk A2, Van Houtte N1, Genné D3, Gomez-Chamorro A3, van Oers K4, Voordouw MJ3.
Author information
1
Evolutionary Ecology Group, Department of Biology, University of Antwerp, Belgium.
2
Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
3
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Switzerland.
4
Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands.
Abstract
The spirochete bacterium Borrelia afzelii is the most common cause of Lyme borreliosis in Europe. This tick-borne pathogen can establish systemic infections in rodents but not in birds. However, several field studies have recovered larval Ixodes ricinus ticks infected with B. afzelii from songbirds suggesting successful transmission of B. afzelii. We reviewed the literature to determine which songbird species were the most frequent carriers of B. afzelii-infected I. ricinus larvae and nymphs. We tested experimentally whether B. afzelii is capable of co-feeding transmission on two common European bird species, the blackbird (Turdus merula) and the great tit (Parus major). For each bird species, four naïve individuals were infested with B. afzelii-infected I. ricinus nymphal ticks and pathogen-free larval ticks. None of the co-feeding larvae tested positive for B. afzelii in blackbirds, but a low percentage of infected larvae (3.33%) was observed in great tits. Transstadial transmission of B. afzelii DNA from the engorged nymphs to the adult ticks was observed in both bird species. However, BSK culture found that these spirochetes were not viable. Our study suggests that co-feeding transmission of B. afzelii is not efficient in these two songbird species.
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26.) Borrelia sp. phylogenetically different from Lyme disease- and relapsing fever-related Borrelia spp. in Amblyomma varanense from Python reticulatus.
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Parasit Vectors. 2016 Jun 24;9(1):359. doi: 10.1186/s13071-016-1629-8.
Trinachartvanit W1, Hirunkanokpun S2, Sudsangiem R1, Lijuan W3, Boonkusol D4, Baimai V1,5, Ahantarig A6,7.
Author information
1
Biodiversity Research Cluster, Department of Biology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand.
2
Department of Biology, Faculty of Science, Ramkhamhaeng University, Ramkhamhaeng Road, Bangkok, 10240, Thailand.
3
Department of Science Education, Faculty of Science and Technology, Thepsatri Rajabhat University, Maung, Lopburi, 15000, Thailand.
4
Department of Biology, Faculty of Science and Technology, Thepsatri Rajabhat University, Maung, Lopburi, 15000, Thailand.
5
Center of Excellence for Vectors and Vector-Borne Diseases, Faculty of Science, Mahidol University at Salaya, Phutthamonthon 4 Road, Nakhon Pathom, 73170, Thailand.
6
Biodiversity Research Cluster, Department of Biology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand. arunee.aha@mahidol.ac.th.
7
Center of Excellence for Vectors and Vector-Borne Diseases, Faculty of Science, Mahidol University at Salaya, Phutthamonthon 4 Road, Nakhon Pathom, 73170, Thailand. arunee.aha@mahidol.ac.th.
Abstract
BACKGROUND:
Species of the genus Borrelia are causative agents of Lyme disease and relapsing fever. Lyme disease is the most commonly reported vector-borne disease in the northern hemisphere. However, in some parts of the world Lyme borreliosis and relapsing fever may be caused by novel Borrelia genotypes. Herein, we report the presence of a Borrelia sp. in an Amblyomma varanense collected from Python reticulatus.
METHODS:
Ticks were collected from snakes, identified to species level and examined by PCR for the presence of Borrelia spp. flaB and 16S rRNA genes. Phylogenetic trees were constructed using the neighbour-joining method.
RESULTS:
Three A. varanense ticks collected from P. reticulatus were positive for a unique Borrelia sp., which was phylogenetically divergent from both Lyme disease- and relapsing fever-associated Borrelia spp.
CONCLUSION:
The results of this study suggest for the first time that there is a Borrelia sp. in A. varanense tick in the snake P. reticulatus that might be novel.
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27.) [Ixodes ricinus, transmitted diseases and reservoirs].
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Parassitologia. 2004 Jun;46(1-2):119-22.
[Article in Italian]
Rizzoli A1, Rosà R, Mantelli B, Pecchioli E, Hauffe H, Tagliapietra V, Beninati T, Neteler M, Genchi C.
Author information
1
Centro di Ecologia Alpina, Viote del Monte Bondone, 38040, Trento, Italy.
Abstract
The tick Ixodes ricinus has been recorded in most Italian regions especially in thermo-mesophilous woods and shrubby habitats where the relative humidity allow the tick to complete its 3 year developmental cycle, as predicted for the European climatic ranges. This tick acts both as vector and reservoir for a series of wildlife zoonotic pathogens, especially the agents of Lyme diseases, Tick borne encephalitis and Human Granulocytic Ehrlichiosis, which are emerging in most of Europe. To assess the spatial distribution of these pathogens and the infection risk for humans and animals within the territory of the Province of Trento, we carried out a long term study using a combination of eco-epidemiological surveys and mathematical modelling. An extensive tick collection with a GIS based habitat suitability analysis allowed us to identify the areas where tick occurs at various density. To identify the areas with higher infection risk, we estimated the values of R0 for Borrelia burgdorferi s.l., TBE virus and Anaplasma phagocytophila under different ecological conditions. We assessed the infection prevalence in the vector and in the wildlife reservoir species that play a central role in the persistence of these infections, ie the small mammals A. flavicollis and C. glareolus. We also considered the double effect of roe deer (Capreolus capreolus) which act as reservoir for A. phagocytophila but is an incompetent host for B. burgdorferi and TBE virus, thus reducing the infection prevalence in ticks of these last two pathogens. Infection prevalence with B. burgdorferi and A. phagocytophila in the vector was assessed by PCR screening 1212 I. ricinus nymphs collected by dragging in six main study areas during 2002. The mean infection prevalence recorded was 1.32% for B. burgdorferi s.l. and 9.84% for A. phagocytophila. Infection prevalence in nymphs with TBE virus, as assessed in a previous study was 0.03%. Infection prevalence in rodents was assessed by screening (with ELISA and PCR) tissues and blood samples collected from 367 rodent individuals trapped extensively during 2002 within 6 main study areas. A. flavicollis (N=238) was found to be infected with all three pathogens investigated, with infection prevalence ranging from 3.3% for TBE virus to 11.7% for A. phagocytophila, and 16.6% with B. burgdorferi s.l. C. glareolus (N=108) showed an infection prevalence of 6.5% with A. phagocytophila and 12.7% with B. burgdorferi s.l., while no individuals were infected with TBE virus. We also screened 98 spleen samples collected from roe deer with PCR, resulting in a mean prevalence of infection with A. phagocytophila of 19.8%. Using a deterministic model we explored the condition for diseases persistence under different rodent and roe deer densities. R0 values resulted largely above 1 for B. burgdorferi s.l. in the vast majority of the areas classified as suitable for I. ricinus occurrence in Trentino, while the condition for TBE persistence appeared to be more restricted by a combination of climatic condition and host densities.
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28.) ["Reversible" dementia in 2011].
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Geriatr Psychol Neuropsychiatr Vieil. 2011 Jun;9(2):211-25. doi: 10.1684/pnv.2011.0274.
[Article in French]
Michel JM1, Sellal F.
Author information
1
CMRR de Strasbourg-ColmarCMRR de Strasbourg-ColmarCMRR de Strasbourg-Colmar. jeanmarc.michel@ch-colmar.fr
Abstract
Reversible dementias are rare and account for approximately 1.5% of all dementias. The most frequent etiology is represented by neurosurgical causes such as benign tumours, adult chronic hydrocephalus (so-called « normal pressure » hydrocephalus) or subdural hematoma, which are easily revealed by neuroimaging. Systematic ancillary investigations aimed at detecting an infectious disease (syphilis, HIV infection, Lyme neuroborreliosis or, more rarely, Whipple disease), an endocrine aetiology or a vitamin deficiency are rarely contributory, but remain relevant since these dementias could be reversible. Discovering a reversible cause of dementia does not always allow full recovery after treatment. However, systematic ancillary investigations can identify and treat concomitant reversible conditions, which contribute to worsening the main clinical condition in nearly 25% of dementia cases.
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29.) Chronic inflammation and amyloidogenesis in Alzheimer's disease -- role of Spirochetes.
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J Alzheimers Dis. 2008 May;13(4):381-91.
Miklossy J1.
Author information
1
University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada. judithmiklossy@bluewin.ch
Abstract
Alzheimer's disease (AD) is associated with dementia, brain atrophy and the aggregation and accumulation of a cortical amyloid-beta peptide (Abeta). Chronic bacterial infections are frequently associated with amyloid deposition. It had been known from a century that the spirochete Treponema pallidum can cause dementia in the atrophic form of general paresis. It is noteworthy that the pathological hallmarks of this atrophic form are similar to those of AD. Recent observations showed that bacteria, including spirochetes contain amyloidogenic proteins and also that Abeta deposition and tau phosphorylation can be induced in or in vivo following exposure to bacteria or LPS. Bacteria or their poorly degradable debris are powerful inflammatory cytokine inducers, activate complement, affect vascular permeability, generate nitric oxide and free radicals, induce apoptosis and are amyloidogenic. All these processes are involved in the pathogenesis of AD. Old and new observations, reviewed here, indicate that to consider the possibility that bacteria, including several types of spirochetes highly prevalent in the population at large or their persisting debris may initiate cascade of events leading to chronic inflammation and amyloid deposition in AD is important, as appropriate antibacterial and antiinflammatory therapy would be available to prevent dementia.
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30.) Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
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J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 673-81.
Miklossy J1, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.
Author information
1
University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland. judmik@telus.net
Abstract
The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.
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31.) Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes.
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Neurobiol Aging. 2006 Feb;27(2):228-36.
Miklossy J1, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K.
Author information
1
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3. judmik@telus.net
Abstract
The pathological hallmarks of Alzheimer's disease (AD) consist of beta-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of beta-amyloid precursor protein (AbetaPP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.
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32.) Alzheimer's disease--a spirochetosis?
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Neuroreport. 1993 Jul;4(7):841-8.
Miklossy J1.
Author information
1
Division of Neuropathology, University of Lausanne, Switzerland.
Abstract
The aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (beta A4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the beta amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the beta amyloid deposited in the AD brain.
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33.) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
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J Neuroinflammation. 2011 Aug 4;8:90. doi: 10.1186/1742-2094-8-90.
Miklossy J1.
Author information
1
International Alzheimer Research Center, Prevention Alzheimer Foundation, Martigny-Combe, Switzerland. judithmiklossy@bluewin.ch
Abstract
It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.
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34.) Link between chronic bacterial inflammation and Alzheimer disease.
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CNS Neurol Disord Drug Targets. 2014;13(7):1140-7.
Bibi F, Yasir M, Sohrab SS, Azhar EI, Al-Qahtani MH, Abuzenadah AM, Kamal MA, Naseer MI1.
Author information
1
Center of Excellence in Genomic Medicine and Research (CEGMR), King Abdulaziz University Jeddah 21589, Saudi Arabia. mimrannaseer@yahoo.com.
Abstract
Alzheimer's disease (AD) is a degenerative disease of brain that is associated with dementia, brain atrophy, accumulation of hyperphosphorylated tau protein and amyloid-beta peptide in hippocampus and cortex region of the brain. The development of AD is a multifactorial process that may also involve infection with bacterial pathogens. Recent studies suggest that bacteria including spirochetes have the potential to initiate cascade of events, leading to inflammatory condition of the central nervous system. Bacteria and spirochetes are activators of proinflammatory cytokines, generate free radicals, nitric oxide and further induction of apoptosis. Infection with these microbes may be considered as a risk factor for pathophysiology of AD or to cognitive changes. Recent studies have revealed that exposure to these microorganisms induces Aβ accumulation and tau protein phosphorylation, and chronic infections with these pathogenic bacteria can possibly contribute to progression of AD. In this article, we update and review the role of bacteria in the pathogenesis of AD resulting from initiation of cascade events in chronic inflammations and amyloidogenesis. Controlling these chronic infections with antibacterial or anti-inflammatory drugs will allow preventing inflammation, a risk factor for AD.
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35.) Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?
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Alzheimers Dement. 2009 Jul;5(4):348-60. doi: 10.1016/j.jalz.2008.12.001.
Honjo K1, van Reekum R, Verhoeff NP.
Author information
1
L.C. Campbell Cognitive Neurology Research Unit, Heart and Stroke Foundation Centre for Stroke Recovery, Section of Neurology, Department of Medicine, Sunnybrook Health Science Centre and University of Toronto, Toronto, Ontario, Canada.
Abstract
Infection with several important pathogens could constitute risk factors for cognitive impairment, dementia, and Alzheimer's disease (AD) in particular. This review summarizes the data related to infectious agents that appear to have a relationship with AD. Infections with herpes simplex virus type 1, picornavirus, Borna disease virus, Chlamydia pneumoniae, Helicobacter pylori, and spirochete were reported to contribute to the pathophysiology of AD or to cognitive changes. Based on these reports, it may be hypothesized that central nervous system or systemic infections may contribute to the pathogenesis or pathophysiology of AD, and chronic infection with several pathogens should be considered a risk factor for sporadic AD. If this hypothesis holds true, early intervention against infection may delay or even prevent the future development of AD.
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36.) Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.
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Harris SA1, Harris EA2.
Author information
1
St. Vincent Medical Group, Northside Internal Medicine, Indianapolis, IN, USA.
2
Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract
This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.
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37.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
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Antibiotics (Basel). 2017 Mar 22;6(1). pii: E10. doi: 10.3390/antibiotics6010010.
Feng J1, Zhang S2, Shi W3, Zhang Y4.
Author information
1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. jfeng16@jhu.edu.
2
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. szhang30@jhu.edu.
3
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. wshi3@jhu.edu.
4
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu.
Abstract
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug-containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
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38.) Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.
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Carris NW1, Pardo J2, Montero J3, Shaeer KM4.
Author information
1
Department of Pharmacotherapeutics and Clinical Research , University of South Florida College of Pharmacy ; Departments of Family Medicine.
2
Department of Pharmacy , North Florida/South Georgia Veterans Health System , Gainesville.
3
Internal Medicine , University of South Florida, Morsani College of Medicine , Tampa.
4
Department of Pharmacotherapeutics and Clinical Research , University of South Florida College of Pharmacy ; Internal Medicine , University of South Florida, Morsani College of Medicine , Tampa.
Abstract
Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.
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39.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
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Antimicrob Agents Chemother. 2010 Feb;54(2):643-51. doi: 10.1128/AAC.00788-09. Epub 2009 Dec 7.
Barthold SW1, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.
Author information
1
Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. swbarthold@ucdavis.edu
Abstract
The effectiveness of a new first-in-class antibiotic, tigecycline (glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of tigecycline, saline (negative-effect controls), or a previously published regimen of ceftriaxone (positive-effect controls). Infection status was assessed at 3 months after treatment by culture, quantitative ospA real-time PCR, and subcutaneous transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with antibiotics were ospA PCR positive, although the DNA marker load was markedly decreased compared to that in saline-treated mice. Antibiotic treatment during the early stage of infection appeared to be more effective than treatment that began during later stages of infection. The viability of noncultivable spirochetes in antibiotic-treated mice (demonstrable by PCR) was confirmed by transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from antibiotic-treated mice revealed RNA transcription of several B. burgdorferi genes. These results extended previous studies with ceftriaxone, indicating that antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.
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40.) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?
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Med Hypotheses. 2005;64(3):438-48.
Fritzsche M1.
Author information
1
Clinic for Internal and Geographical Medicine, Soodstrasse 13, 8134 Adliswil, Switzerland. markus.fritzsche@gmx.ch
Abstract
Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet. Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks. In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable. As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted. The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS. Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls. Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be large enough and preferably taken together in a multi-centre study
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41.) [Minocycline].
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Ann Dermatol Venereol. 2001 May;128(5):627-37.
[Article in French]
Bernier C1, Dréno B.
Author information
1
Clinique Dermatologique, Hôtel-Dieu, Place Alexis Ricordeau, 44093 Nantes Cedex 1.
Abstract
Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treonema and Proprionibacterium acenes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.
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42.) Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis.
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Infection. 1996 Jan-Feb;24(1):69-72.
Breier F1, Kunz G, Klade H, Stanek G, Aberer E.
Author information
1
Universitätsklinik für Dermatologie, Wien, Austria.
Abstract
An open, randomized, prospective study was carried out to compare the clinical efficacy and safety of phenoxymethylpenicillin with that of minocycline in the treatment of erythema migrans. Sixty patients (minocycline 30, penicillin 30) were enrolled in the study. The two groups of patients were statistically homogeneous regarding age and sex distribution. IgG and IgM antibodies against Borrelia burgdorferi were determined by ELISA before and after treatment and 1 year thereafter. Thirty-nine patients completed the study. All these patients (penicillin 21, minocycline 18) who received a 21-day course of treatment were free of clinical symptoms of late Lyme borreliosis after 1 year. Serum antibodies against B. burgdorferi could be detected before treatment in 6/21 patients treated with penicillin and 3/18 patients treated with minocycline. After 1 year 8/39 patients were seropositive without any evidence of ongoing disease. In the remaining 21 patients treatment could not be completed with the initial antibiotic due to side effects (penicillin 9/30, minocycline 12/30). One patient, who stopped penicillin treatment at day 14 and one patient who stopped minocycline at day 4, developed fatigue and memory impairment within the observation period. A 3-week course of treatment with penicillin or minocycline is equally effective in treating patients with erythema migrans and preventing late symptoms of Lyme borreliosis.
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43.) Influence of tick and mammalian physiological temperatures on Borrelia burgdorferi biofilms.
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Microbiology. 2016 Nov;162(11):1984-1995. doi: 10.1099/mic.0.000380.
Shaikh S1, Timmaraju VA1, Torres JP1, Socarras KM1, Theophilus PA1, Sapi E1.
Author information
Abstract
The spirochaete bacterium Borrelia burgdorferisensu lato is the aetiologic agent of Lyme disease. Borrelia is transmitted to mammals through tick bite and is adapted to survive at tick and mammalian physiological temperatures. We have previously shown that B. burgdorferi can exist in different morphological forms, including the antibiotic-resistant biofilm form, in vitro and in vivo. B. burgdorferi forms aggregates in ticks as well as in humans, indicating potential of biofilm formation at both 23 and 37 °C. However, the role of various environmental factors that influence Borrelia biofilm formation remains unknown. In this study, we investigated the effect of tick (23 °C), mammalian physiological (37 °C) and standard in vitro culture (33 °C) temperatures with the objective of elucidating the effect of temperature on Borrelia biofilm phenotypes invitro using two B. burgdorferisensu stricto strains (B31 and 297). Our findings show increased biofilm quantity, biofilm size, exopolysaccharide content and enhanced adherence as well as reduced free spirochaetes at 37 °C for both strains, when compared to growth at 23 and 33 °C. There were no significant variations in the biofilm nano-topography and the type of extracellular polymeric substance in Borrelia biofilms formed at all three temperatures. Significant variations in extracellular DNA content were observed in the biofilms of both strains cultured at the three temperatures. Our results indicate that temperature is an important regulator of Borrelia biofilm development, and that the mammalian physiological temperature favours increased biofilm formation in vitro compared to tick physiological temperature and in vitro culture temperature.
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44.) Cimetidine as a novel adjunctive treatment for early stage Lyme disease.
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Med Hypotheses. 2016 Apr 9. pii: S0306-9877(16)30007-X. doi: 10.1016/j.mehy.2016.03.015. [Epub ahead of print]
Shemenski J1.
Author information
1
D'Youville College, 320 Porter ave, Buffalo, NY 14201, United States. Electronic address: Shemej25@dyc.edu.
Abstract
Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease.
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45.) Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas.
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Eur J Microbiol Immunol (Bp). 2016 Feb 9;6(1):9-24. doi: 10.1556/1886.2015.00049. eCollection 2016.
Sapi E1, Balasubramanian K1, Poruri A1, Maghsoudlou JS1, Socarras KM1, Timmaraju AV1, Filush KR1, Gupta K1, Shaikh S1, Theophilus PA1, Luecke DF1, MacDonald A1, Zelger B2.
Author information
1
Department of Biology and Environmental Science, University of New Haven , West Haven, CT 06516, USA.
2
Department of Dermatology and Venereology, Medical University Innsbruck , Innsbruck, Austria.
Abstract
Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues.
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2.) Can infections cause Alzheimer's disease?
3.) No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.
4.) Lyme neuroborreliosis and dementia.
5.) Cerebrovascular Events in Lyme Neuroborreliosis.
6.) Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a
multicentre, non-inferiority, double-blind, randomised trial.
7.) Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis and management.
8.) Lyme disease associated neuroretinitis - Case report.
9.) Neuroretinitis associated with serologies positive for bartonella henselae and borrelia burgdorferi.
10.) Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.
11.) Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717).
12.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
13.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
14.) Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi.
15.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
16.) In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China.
17.) Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial.
18,) The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic
Lyme Disease/Post Treatment Lyme Disease Syndrome
19.) Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.
20.) Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi.
21.) A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
22.) Comparison of the lifetime host-to-tick transmission between two strains of the Lyme disease pathogen Borrelia afzelii.
23.) Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review.
24.) Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector.
25.) Inefficient co-feeding transmission of Borrelia afzelii in two common European songbirds.
26.) Borrelia sp. phylogenetically different from Lyme disease- and relapsing fever-related Borrelia spp. in Amblyomma varanense from Python reticulatus.
27.) [Ixodes ricinus, transmitted diseases and reservoirs].
28.) ["Reversible" dementia in 2011].
29.) Chronic inflammation and amyloidogenesis in Alzheimer's disease -- role of Spirochetes.
30.) Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
31.) Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes.
32.) Alzheimer's disease--a spirochetosis?
33.) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
34.) Link between chronic bacterial inflammation and Alzheimer disease.
35.) Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?
36.) Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.
37.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
38.) Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.
39.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
40.) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?
41.) [Minocycline].
42.) Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis.
43.) Influence of tick and mammalian physiological temperatures on Borrelia burgdorferi biofilms.
44.) Cimetidine as a novel adjunctive treatment for early stage Lyme disease.
45.) Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas.
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1.) Lyme neuroborreliosis and dementia.
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J Alzheimers Dis. 2014;41(4):1087-93. doi: 10.3233/JAD-130446.
Blanc F1, Philippi N1, Cretin B1, Kleitz C2, Berly L2, Jung B1, Kremer S3, Namer IJ4, Sellal F5, Jaulhac B6, de Seze J7.
Author information
1
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
2
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
3
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Neuroradiology Service, Strasbourg, France.
4
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Nuclear Medicine Service, Strasbourg, France.
5
University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France General Hospital of Colmar, Neurology Service, Colmar, France.
6
University Hospital of Strasbourg, Laboratory of Bacteriology and National Center for Borrelia, Strasbourg, France.
7
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France INSERM U119, Strasbourg, France.
Abstract
INTRODUCTION:
Descriptions of Lyme disease and dementia are rare.
OBJECTIVE:
To describe patients with dementia and a positive "intrathecal anti-Borrelia antibody index" (AI), specific for neuroborreliosis.
METHODS:
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years.
RESULTS:
We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer's disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second.
CONCLUSION:
Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.
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2.) Can infections cause Alzheimer's disease?
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Epidemiol Rev. 2013;35:161-80. doi: 10.1093/epirev/mxs007. Epub 2013 Jan 24.
Mawanda F, Wallace R.
Abstract
Late-onset Alzheimer's disease (AD) is the most prevalent cause of dementia among older adults, yet more than a century of research has not determined why this disease develops. One prevailing hypothesis is that late-onset AD is caused by infectious pathogens, an idea widely studied in both humans and experimental animal models. This review examines the infectious AD etiology hypothesis and summarizes existing evidence associating infectious agents with AD in humans. The various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD are considered, as is the concordance between putative infectious agents and the epidemiology of AD. We searched the PubMed, Web of Science, and EBSCO databases for research articles pertaining to infections and AD and systematically reviewed the evidence linking specific infectious pathogens to AD. The evidence compiled from the literature linking AD to an infectious cause is inconclusive, but the amount of evidence suggestive of an association is too substantial to ignore. Epidemiologic, clinical, and basic science studies that could improve on current understanding of the associations between AD and infections and possibly uncover ways to control this highly prevalent and debilitating disease are suggested.
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3.) No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.
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Emerg Infect Dis. 2015 Nov;21(11):2036-9. doi: 10.3201/eid2111.150778.
Forrester JD, Kugeler KJ, Perea AE, Pastula DM, Mead PS.
Abstract
Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.
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4.) Lyme neuroborreliosis and dementia.
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J Alzheimers Dis. 2014;41(4):1087-93. doi: 10.3233/JAD-130446.
Blanc F1, Philippi N1, Cretin B1, Kleitz C2, Berly L2, Jung B1, Kremer S3, Namer IJ4, Sellal F5, Jaulhac B6, de Seze J7.
Author information
1
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
2
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France.
3
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Neuroradiology Service, Strasbourg, France.
4
University of Strasbourg and CNRS, ICube Laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg) Strasbourg, France University Hospital of Strasbourg, Nuclear Medicine Service, Strasbourg, France.
5
University Hospital of Strasbourg, CMRR (Memory Resource and Research Center), Strasbourg, France General Hospital of Colmar, Neurology Service, Colmar, France.
6
University Hospital of Strasbourg, Laboratory of Bacteriology and National Center for Borrelia, Strasbourg, France.
7
University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France INSERM U119, Strasbourg, France.
Abstract
INTRODUCTION:
Descriptions of Lyme disease and dementia are rare.
OBJECTIVE:
To describe patients with dementia and a positive "intrathecal anti-Borrelia antibody index" (AI), specific for neuroborreliosis.
METHODS:
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years.
RESULTS:
We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer's disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second.
CONCLUSION:
Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.
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5.) Cerebrovascular Events in Lyme Neuroborreliosis.
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J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1671-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.056. Epub 2015 May 20.
Wittwer B1, Pelletier S2, Ducrocq X1, Maillard L1, Mione G1, Richard S3.
Author information
1
Stroke Unit, Department of Neurology, CHU Nancy, Hopital Central, Nancy Cedex, France.
2
Stroke Unit, CH Bar le Duc, Bar le Duc Cedex, France.
3
Stroke Unit, Department of Neurology, CHU Nancy, Hopital Central, Nancy Cedex, France. Electronic address: s.richard@chu-nancy.fr.
Abstract
BACKGROUND:
Cerebrovascular events in neuroborreliosis are a rare condition described only in isolated or small case series. No specific clinical or radiological features have been identified, and diagnosis is based on very different criteria.
METHODS:
We retrospectively describe cases diagnosed in the Stroke Unit of Nancy Hospital, located in the endemic area of the northeast of France. We also reviewed other cases found in the literature.
RESULTS:
We identified 5 cases in our center and 57 other reported cases. Mean age was 39 years (range 5 to 77). Possible previous contact with Borrelia burgdorferi (B burgdorferi) was found in about half of cases. Additional neurologic symptoms (headache, cognitive impairment, and/or gait disturbance) were found in 44% of cases. Cerebral imaging revealed both ischemic (87%) and hemorrhagic lesions (13%) with a multiterritorial aspect in 22% of strokes, and signs of vasculitis in 71%. Analysis of cerebrospinal fluid (CSF) revealed lymphocytic meningitis in 90% of cases and elevated protein level in 86%. CSF/serum anti-B burgdorferi antibody index (AI) was positive in 91% of cases. Outcome was favorable after appropriate antibiotic treatment. Our 5 patients presented a modified Rankin scale score 0-1, without any stroke recurrence, after a median follow-up of 2.8 years.
CONCLUSIONS:
The diagnosis of Lyme neuroborreliosis should be considered for patients with cerebrovascular events without obvious cause living in an endemic area, in the presence of repeat multiterritorial strokes at short intervals, other neurologic symptoms, a history of B burgdorferi infection, and radiological signs of vasculitis. Diagnosis can be confirmed by CSF analysis with AI but with an incomplete sensitivity.
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6.) Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a
multicentre, non-inferiority, double-blind, randomised trial.
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Lancet Neurol. 2008 Aug;7(8):690-5. doi: 10.1016/S1474-4422(08)70119-4. Epub 2008 Jun 21.
Ljøstad U1, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A.
Author information
1
Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway. unn.ljostad@sshf.no
Erratum in
Lancet Neurol. 2008 Aug;7(8):675.
Abstract
BACKGROUND:
Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis.
METHODS:
From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801.
FINDINGS:
Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events.
INTERPRETATION:
Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.
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7.) Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis and management.
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Indian J Ophthalmol. 2017 Mar;65(3):250-252. doi: 10.4103/ijo.IJO_151_17.
Guliani BP1, Kumar S1, Chawla N2, Mehta A1.
Author information
1
Department of Ophthalmology, VMMC and Safdarjung Hospital, New Delhi, India.
2
Department of Ophthalmology, Sanjay Gandhi Memorial Hospital, New Delhi, India.
Abstract
We present a case of neuroretinitis as presenting and the only presentation of Lyme disease in a 25-year-old female who visited hilly areas in the Himalayas of North India. She presented with right eye sudden and painless blurring of vision. Her vision at presentation was 20/60. She had fundus examination; fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) imaging showed classical features of neuroretinitis. No other organ was involved. Oral steroids were prescribed and relevant investigations sent for noninfective and infective causes. Worsened visual acuity (VA) to hand movement and positive IgM titers for Borrelia burgdorferi led to the diagnosis of Lyme disease-associated neuroretinitis. Treatment with oral doxycycline plus oral steroids for 4 weeks revealed VA of 20/20 and resolution of fundus and OCT changes. Neuroretinitis as presenting and the only presentation of Lyme disease will be discussed with serial fundus, FFA, and OCT pictures.
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8.) Lyme disease associated neuroretinitis - Case report.
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Acta Microbiol Immunol Hung. 2015 Dec;62(4):403-8. doi: 10.1556/030.62.2015.4.5.
Vanya M1, Fejes I2, Jako M1, Tula A3, Terhes G4, Janaky M2, Bartfai G1.
Author information
1
Department of Obstetrics and Gynaecology, Faculty of Medicine, Albert Szent-Gyorgyi Clinical Centre, University of Szeged , Szeged , Hungary.
2
Department of Ophthalmology, Faculty of General Medicine, Albert Szent-Gyorgyi Clinical Centre University of Szeged , Szeged , Hungary.
3
Department of Obstetrics and Gynaecology, Riga Stradiņš University , Riga , Latvia.
4
Department of Clinical Microbiology, Faculty of General Medicine, Albert Szent-Gyorgyi Clinical Centre, University of Szeged , Szeged , Hungary.
Abstract
We describe a rare case of Lyme disease complicated by unilateral neuroretinitis in the right eye. We report a case of a 27-year-old woman with blurred vision on her right eye. Because of the suspicion of optic neuritis (multiplex sclerosis) neurological examination was ordered. Surprisingly, computer tomography of the brain revealed incomplete empty sella, which generally results not monocular, but bilateral optic nerve swelling. Opthalmological examination (ophthalmoscopy and optical coherence tomography) indicated not only monocular optic nerve, but retinal oedema next to the temporal part of the right optic disk. Visual evoked potentials (VEP) demonstrated no P100 latency delay and mild differences between the amplitudes of the responses of the left and right eye. Optical coherence tomography (OCT) demonstrated the swelling of the optic nerve head and oedematous retina at the temporal part of the disk. Suspicion of an inflammatory cause of visual disturbance blood tests was ordered. Doxycycline treatment was ordered till the result of the blood test arrived. The Western blot and ELISA test were positive for Borrelia burgdorferi sensu lato. Following one week corticosteroide and ceftriaxone treatments, the patient displayed a clinical improvement. Unilateral neuroretinitis with optic disk swelling due to neuroborreliosis is a rare complication and in many cases it is difficult to distinguish between inflammatory and ischemic lesions. Further difficulty in the diagnosis can occur when intracranial alterations such as empty sella is demonstrated by CT examination.
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9.) Neuroretinitis associated with serologies positive for bartonella henselae and borrelia burgdorferi.
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Retin Cases Brief Rep. 2009 Summer;3(3):243-4. doi: 10.1097/ICB.0b013e31816bbec1.
Modjtahedi SP1, Truong SN, Gray AV, Morse LS.
Author information
1
From the Department of Ophthalmology & Vision Science, University of California at Davis Medical Center, Sacramento, California.
Abstract
PURPOSE:
To describe a patient with neuroretinitis with features of both cat-scratch disease and Lyme disease who had serologies positive for both Bartonella henselae and Borrelia burgdorferi.
METHODS:
Case report of a single individual undergoing diagnostic testing and treatment for neuroretinitis.
RESULTS:
A 47-year-old woman developed acute painless loss of vision and was found to have neuroretinitis. Diagnostic workup yielded serologies positive for both B. henselae and B. burgdorferi. The patient was treated with oral antibiotics for coverage of both etiologies, and her condition improved.
CONCLUSION:
Serologies positive for both B. henselae and B. burgdorferi can be obtained in the workup of neuroretinitis. Clinicians should be aware and use clinical judgment in guiding their diagnosis and treatment of neuroretinitis.
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10.) Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.
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BMC Nephrol. 2017 Feb 6;18(1):51. doi: 10.1186/s12882-017-0462-4.
Florens N1,2,3, Lemoine S4,5,6, Guebre-Egziabher F4,6, Valour F7, Kanitakis J8,9, Rabeyrin M9, Juillard L4,5,6.
Author information
1
Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, 69437, Lyon, Cedex 03, France. nans.florens@gmail.com.
2
Université Claude Bernard Lyon 1, Villeurbanne, France. nans.florens@gmail.com.
3
INSERM U1060, CarMeN, Université Claude Bernard Lyon 1, Lyon, France. nans.florens@gmail.com.
4
Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, 69437, Lyon, Cedex 03, France.
5
Université Claude Bernard Lyon 1, Villeurbanne, France.
6
INSERM U1060, CarMeN, Université Claude Bernard Lyon 1, Lyon, France.
7
Department of Infectious and Tropical Diseases, Hospices Civils de Lyon, Lyon, France.
8
Deparment of Dermatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
9
Department of Pathology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
Abstract
BACKGROUND:
There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis.
CASE PRESENTATION:
A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids.
CONCLUSION:
We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.
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11.) Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717).
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Int J Syst Evol Microbiol. 2017 Jan 27. doi: 10.1099/ijsem.0.001815. [Epub ahead of print]
Barbour AG1, Adeolu M2, Gupta RS3.
Author information
1
1Departments of Medicine, Microbiology & Molecular Genetics, and Ecology & Evolutionary Biology, University of California Irvine, Irvine, California, USA.
2
2Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
3
3McMaster University.
Abstract
This rebuttal Letter responds to a Letter in the IJSEM by Margos et al. challenging division of the genus Borrelia into two genera. We discuss here point-by-point the issues raised by Margos et al. and show that much of their criticism is unfounded and in several cases based on misreading of the presented results. We summarize here the extensive evidence based on genomic, genetic and phenotypic properties showing that the members of the family Borreliaceae (containing mainly the genus Borrelia) comprises two distinct and cohesive groups of microbes, differing in diseases they cause and other phenotypes. Prior to the proposed division, Borrelia spp. causing Lyme disease (LD) were already functionally treated as a distinct group, referred to as "B. burgdorferi sensu lato" to distinguish them from the other cluster of Borrelia spp. which includes all known species causing relapsing fever (RF). With the more explicit division of Borreliaceae species into two genus level groups, which are distinguishable from each other based on numerous unique genetic and molecular characteristics, the attention can now be focused on the biological significance of different molecular characteristics differentiating the two groups. The clear distinction of the LD and the RF groups of microbes based on numerous highly reliable markers, which are expected to be present even in uncharacterized members of these two groups, should aid in the improved diagnosis as well treatment of both these diseases, which is hindered by the conflation of a common name for agents causing two different types of diseases.
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12.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
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Antibiotics (Basel). 2017 Mar 22;6(1). pii: E10. doi: 10.3390/antibiotics6010010.
Feng J1, Zhang S2, Shi W3, Zhang Y4.
Author information
1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. jfeng16@jhu.edu.
2
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. szhang30@jhu.edu.
3
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. wshi3@jhu.edu.
4
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu.
Abstract
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug-containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
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13.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
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J Infect Dis. 2009 May 1;199(9):1379-88. doi: 10.1086/597807.
Bernardino AL1, Kaushal D, Philipp MT.
Author information
1
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
Abstract
Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP-1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated. Functionally, phosphorylation of IkappaBalpha and binding of NF-kappaB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.
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14.) Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi.
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Ticks Tick Borne Dis. 2010 Mar;1(1):30-4. doi: 10.1016/j.ttbdis.2009.11.004. Epub 2010 Jan 7.
Ates L1, Hanssen-Hübner C, Norris DE, Richter D, Kraiczy P, Hunfeld KP.
Author information
1
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt/Main, Germany.
Abstract
Tigecycline is a new glycylcycline that has recently been revealed to be very effective in vitro against a variety of Gram-negative and Gram-positive bacteria including multi-drug resistant microorganisms. Using a standardized microdilution susceptibility testing method, we determined the minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) of tigecycline, in parallel with doxycycline, tetracycline, and other antibiotic agents relevant for Lyme borreliosis treatment such as ceftriaxone and cefotaxime. The activity of all agents against 16 different Borrelia isolates belonging to all borrelial genospecies known to be pathogenic for humans was investigated and analyzed under standardized conditions. The overall rank order of MIC(90)s was tigecycline (≤0.016 mg/L) > ceftriaxone (0.03 mg/L) > cefotaxime (≤0.125 mg/L) > doxycycline (0.25 mg/L) > tetracycline (0.25 mg/L). The rank order of MBC(90)s was tigecycline (0.5 mg/L) > ceftriaxone (2 mg/L) > tetracycline (16 mg/L) > doxycycline (16 mg/L) > cefotaxime (>16 mg/L). High in vitro activity of the new glycylcycline against Borrelia was further substantiated by time-kill experiments performed with B. afzelii isolate EB1. Parallel testing of tigecycline and ceftriaxone demonstrated a bacteriostatic effect for 0.016 mg/L of tigecycline and for 0.03 mg/L for ceftriaxone after 72 h of incubation. Moreover, tigecycline was bactericidal at a concentration of 0.25 mg/L showing a >3 log(10) unit reduction of the initial inoculum, whereas for ceftriaxone a concentration of 2 mg/L was needed.
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15.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
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Barthold SW1, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.
Author information
1
Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. swbarthold@ucdavis.edu
Abstract
The effectiveness of a new first-in-class antibiotic, tigecycline (glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of tigecycline, saline (negative-effect controls), or a previously published regimen of ceftriaxone (positive-effect controls). Infection status was assessed at 3 months after treatment by culture, quantitative ospA real-time PCR, and subcutaneous transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with antibiotics were ospA PCR positive, although the DNA marker load was markedly decreased compared to that in saline-treated mice. Antibiotic treatment during the early stage of infection appeared to be more effective than treatment that began during later stages of infection. The viability of noncultivable spirochetes in antibiotic-treated mice (demonstrable by PCR) was confirmed by transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from antibiotic-treated mice revealed RNA transcription of several B. burgdorferi genes. These results extended previous studies with ceftriaxone, indicating that antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.
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16.) In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China.
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J Infect Chemother. 2000 Mar;6(1):65-7.
Li M1, Masuzawa T, Wang J, Kawabata M, Yanagihara Y.
Author information
1
International Center for Medical Research, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan. muqingl@kobe-u.ac.jp
Abstract
The antibiotic susceptibilities of seven Borrelia burgdorferi sensu lato isolates from Ixodes persulcatus in China were examined by in-vitro microdilution minimum inhibition concentration (MIC) and macrodilution minimum bactericidal concentration (MBC) methods. All isolates tested were susceptible to amoxicillin, erythromycin, and minocycline. The MICs of these drugs for the Chinese isolates were 0.025-0.1 microg/ml, <0.012-0.05 microg/ml, and <0.012-0.05 microg/ml, respectively. The MBCs were 0.1-0.39 microg/ml, <0.012-0.2 microg/ml, and 0.025-0.39 microg/ml, respectively. The in-vivo antimicrobial susceptibilities of the Chinese Borrelia isolates to two test drugs, amoxicillin and minocycline, were evaluated using ddY mice. Mice were infected by subcutaneous inoculation into the right hind footpad. When infection was confirmed, the mice were treated by subcutaneous injection of the test drugs into the back. Amoxicillin and minocycline, which possessed high in-vitro activities against Lyme disease Borrelia, provided good protection against borreliosis in this animal model. Higher doses of these drugs resulted in elimination of the Lyme disease spirochete from all animals receiving this course of treatment. The 50% curative doses (CD50) of amoxicillin and minocycline were 8.7 mg/kg and 3.1 mg/kg, respectively. This suggested that amoxicillin and minocycline could be useful for the treatment of Chinese Borrelia infection.
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17.) Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial.
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BMC Infect Dis. 2016 Feb 4;16:67. doi: 10.1186/s12879-016-1385-6.
Kumar R1, Basu A2, Sinha S3, Das M4, Tripathi P5, Jain A6, Kumar C7, Atam V8, Khan S9, Singh AS10.
Author information
1
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. rashmik2005@gmail.com.
2
National Brain Research Centre, Manesar, Haryana, 122051, India. anirban@nbrc.ac.in.
3
National Brain Research Centre, Manesar, Haryana, 122051, India. subrata.sinha@nbrc.ac.in.
4
INCLEN Trust International, Okhla Industrial Area, Phase-1, New Delhi, 110020, India. manoj@inclentrust.org.
5
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. piyush.tripathi@gmail.com.
6
Departments of Microbiology, King George's Medical University, Lucknow, UP, 226003, India. amita602002@yahoo.com.
7
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. dr_chandrakanta@yahoo.co.in.
8
Departments of Medicine, King George's Medical University, Lucknow, UP, 226003, India. v_atam@yahoo.com.
9
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. saima.firdaus@gmail.com.
10
Departments of Pediatrics, King George's Medical University, Lucknow, UP, 226003, India. amitkgmumedicine@gmail.com.
Abstract
BACKGROUND:
Acute encephalitis syndrome (AES) is a public health problem in India. Neuroinfections are believed to be the most important etiology. Minocycline is a semisythetic tetracycline having excellent penetration into cerebrospinal fluid, established neuroprotective and antiviral properties besides action on nonviral causes of AES. It has been shown to be effective in animal model of Japanese encephalitis (JE). A randomized, controlled trial of nasogastric/oral minocycline in JE and AES at a single centre in Uttar Pradesh, northern India, was therefore conducted.
METHODS:
Patients beyond 3 years of age - but excluding women aged 16-44 years - hospitalized with AES of < =7 days duration were enrolled and block randomized to receive nasogastric/oral minocycline or placebo suspension and followed up. Patients, study personnel and those entering data were blinded as to drug or placebo received. Primary outcome was cumulative mortality at 3 months from hospitalization. Analysis was by intention to treat.
RESULTS:
281 patients were enrolled, 140 received drug and 141 placebo. While there was no overall statistically significant difference in 3 month mortality between drug and placebo groups [RR = 0 · 83 (0 · 6-1 · 1)], there were encouraging trends in patients older than 12 years [RR = 0.70 (0.41-1.18)] and in Glasgow Outcome Score (GOS) at 3 months (χ(2) = 7 · 44, p = 0 · 059). These trends were further accentuated if patients dying within one day of reaching hospital were excluded [OR for 3 month mortality =0 · 70 (0 · 46-1 · 07), p = 0.090; 3 month GOS p = 0 · 028].
CONCLUSIONS:
A trend towards better outcomes was observed with minocycline, especially in those patients who survived the initial day in hospital. These findings should form the basis for planning a larger study and possibly including minocycline in the initial management of AES as seen here.
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18,) The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic
Lyme Disease/Post Treatment Lyme Disease Syndrome
=========================================================
Richard I Horowitz, MD and Phyllis Freeman, PhD
Hudson Valley Healing Arts Center, New York, USA
Corresponding author:
Richard I Horowitz, M.D. Medical Director, Hudson Valley Healing Arts Center, 4232 Albany Post Road, Hyde Park, New York 12538, USA, TTel:845-229-8977; Fax: 845-229-8930; E-mail: medical@hvhac.com
Abstract
Dapsone (diaminodiphenyl sulfone, i.e., DDS) is commonly used to treat dermatological conditions including acne, dermatitis herpetiformis, and leprosy. Mycobacterium leprae, a known "persister" bacteria, requires long-term treatment with intracellular medications including rifampin and Dapsone. Other "persister" bacteria recently have been identified, including Borrelia burgdorferi the agent of Lyme disease.
Objectives:
We tested the efficacy of DDS in patients with chronic Lyme disease/PTLDS with tick-borne co-infections including Babesiosis, who failed commonly used antibiotic and antimalarial protocols.
Methods:
100 patients with Lyme disease, 56 of who were Babesia positive, were placed on Dapsone and folic acid in combination with either one or two other intracellular drugs, including rifampin, tetracyclines, and/or macrolide antibiotics. Several patients also took cephalosporins, and all patients were on protocols to treat cystic forms of Borrelia and biofilms.
Results:
Patients completed a symptom severity survey before beginning treatment with Dapsone and then again after at least one month of treatment scoring their complaints from 0 indicating “none” to 4 indicating “severe” for symptoms including fatigue, joint and/or muscle pain, disturbed sleep, and cognitive difficulties. Results demonstrated that Dapsone significantly improved all patients’ clinical symptoms except for headache, where changes did not reach statistical significance. In addition, Dapsone, known to have anti-malarial effects, helped resistant Babesia symptoms of sweats, chills, and flushing. Lyme positive, Babesia positive patients also demonstrated significant changes in pain, disturbed sleep, and cognitive difficulties. Side effects included macrocytic anemia and rare cases of methemoglobinemia, which resolved by either decreasing the dose of Dapsone or increasing folic acid.
Conclusion:
Dapsone is a novel and effective “persister” drug for those with PTLDS and associated tick-borne co-infections who have failed classical antibiotic protocols. Further prospective trials must determine the DDS dose, length of treatment and best combination antibiotic therapy in order to effect a long-term health benefit.
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19.) Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.
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Microbes Infect. 2016 Jun;18(6):430-5. doi: 10.1016/j.micinf.2016.03.004. Epub 2016 Mar 16.
Van Laar TA1, Hole C1, Rajasekhar Karna SL1, Miller CL1, Reddick R2, Wormley FL1, Seshu J3.
Author information
1
South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
2
The Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, USA.
3
South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA. Electronic address: j.seshu@utsa.edu.
Abstract
Lyme disease (LD) is a systemic disorder caused by Borrelia burgdorferi. Lyme spirochetes encode for a functional 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR EC 1.1.1.88) serving as a rate limiting enzyme of the mevalonate pathway that contribute to components critical for cell wall biogenesis. Statins have been shown to inhibit B. burgdorferi in vitro. Using a mouse model of Lyme disease, we found that statins contribute to reducing bacterial burden and altering the murine immune response to favor clearance of spirochetes.
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20.) Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi.
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PLoS One. 2012;7(5):e38171. doi: 10.1371/journal.pone.0038171. Epub 2012 May 31.
Van Laar TA1, Lin YH, Miller CL, Karna SL, Chambers JP, Seshu J.
Author information
1
Department of Biology, Center for Excellence in Infection Genomics and The University of Texas at San Antonio, San Antonio, Texas, United States of America.
Abstract
Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a K(m) value of 132 µM with a V(max) of 1.94 µmol NADPH oxidized minute(-1) (mg protein)(-1) and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrA(Bb) and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease.
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21.) A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.
=====================================================
Am J Trop Med Hyg. 2008 May;78(5):803-5.
Dolan MC1, Zeidner NS, Gabitzsch E, Dietrich G, Borchert JN, Poché RM, Piesman J.
Author information
1
Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, Colorado 80521, USA. mcd4@cdc.gov
Abstract
The prophylactic and curative potential of doxycycline hyclate formulated in a rodent bait at concentrations of 250 and 500 mg/Kg was evaluated in a murine model of Lyme borreliosis. Both bait formulations prevented tick-transmitted Borrelia burgdorferi infection in 100% of C3H/HeJ mice (N = 16), as well as cured acute, established infection in mice (N = 8) exposed to bait for 14 days. Spirochete infection was cleared in 88.9% to 100% of infected nymphs feeding on mice fed 250 and 500 mg/Kg antibiotic bait formulations, respectively. These data provide evidence for exploring alternative techniques to prevent transmission of Lyme disease spirochetes.
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22.) Comparison of the lifetime host-to-tick transmission between two strains of the Lyme disease pathogen Borrelia afzelii.
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Parasit Vectors. 2016 Dec 16;9(1):645.
Jacquet M1, Margos G2,3, Fingerle V2,3, Voordouw MJ4.
Author information
1
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
2
National Reference Centre for Borrelia, Munich, Oberschleissheim, Germany.
3
Bavarian Health and Food Safety Authority, Munich, Oberschleissheim, Germany.
4
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland. maarten.voordouw@unine.ch.
Abstract
BACKGROUND:
Transmission from the vertebrate host to the arthropod vector is a critical step in the life-cycle of any vector-borne pathogen. How the probability of host-to-vector transmission changes over the duration of the infection is an important predictor of pathogen fitness. The Lyme disease pathogen Borrelia afzelii is transmitted by Ixodes ricinus ticks and establishes a chronic infection inside rodent reservoir hosts. The present study compares the temporal pattern of host-to-tick transmission between two strains of B. afzelii.
METHODS:
Laboratory mice were experimentally infected via tick bite with one of two strains of B. afzelii: A3 and A10. Mice were repeatedly infested with pathogen-free larval Ixodes ricinus ticks over a period of 4 months. Engorged larval ticks moulted into nymphal ticks that were tested for infection with B. afzelii using qPCR. The proportion of infected nymphs was used to characterize the pattern of host-to-tick transmission over time.
RESULTS:
Both strains of B. afzelii followed a similar pattern of host-to-tick transmission. Transmission decreased from the acute to the chronic phase of the infection by 16.1 and 29.3% for strains A3 and A10, respectively. Comparison between strains found no evidence of a trade-off in transmission between the acute and chronic phase of infection. Strain A10 had higher lifetime fitness and established a consistently higher spirochete load in nymphal ticks than strain A3.
CONCLUSION:
Quantifying the relationship between host-to-vector transmission and the age of infection in the host is critical for estimating the lifetime fitness of vector-borne pathogens.
KEYWORDS:
Borrelia afzelii; Co-feeding transmission; Ixodes ricinus; Life-history strategy; Lyme borreliosis; Spirochete; Systemic transmission; Tick-borne pathogen; Vector-borne pathogen
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23.) Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review.
======================================================
Parasit Vectors. 2015 Dec 18;8:643. doi: 10.1186/s13071-015-1257-8.
van Duijvendijk G1, Sprong H2, Takken W3.
Author information
1
Laboratory of Entomology, Wageningen University and Research Centre, Wageningen, The Netherlands. gilian.vanduijvendijk@wur.nl.
2
Laboratory for Zoonosis and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands. hein.sprong@rivm.nl.
3
Laboratory of Entomology, Wageningen University and Research Centre, Wageningen, The Netherlands. willem.takken@wur.nl.
Abstract
The tick Ixodes ricinus is the main vector of the spirochaete Borrelia burgdorferi sensu lato, the causal agent of Lyme borreliosis, in the western Palearctic. Rodents are the reservoir host of B. afzelii, which can be transmitted to I. ricinus larvae during a blood meal. The infected engorged larvae moult into infected nymphs, which can transmit the spirochaetes to rodents and humans. Interestingly, even though only about 1% of the larvae develop into a borreliae-infected nymph, the enzootic borreliae lifecycle can persist. The development from larva to infected nymph is a key aspect in this lifecycle, influencing the density of infected nymphs and thereby Lyme borreliosis risk. The density of infected nymphs varies temporally and geographically and is influenced by multi-trophic (tick-host-borreliae) interactions. For example, blood feeding success of ticks and spirochaete transmission success differ between rodent species and host-finding success appears to be affected by a B. afzelii infection in both the rodent and the tick. In this paper, we review the major interactions between I. ricinus, rodents and B. afzelii that influence this development, with the aim to elucidate the critical factors that determine the epidemiological risk of Lyme borreliosis. The effects of the tick, rodent and B. afzelii on larval host finding, larval blood feeding, spirochaete transmission from rodent to larva and development from larva to nymph are discussed. Nymphal host finding, nymphal blood feeding and spirochaete transmission from nymph to rodent are the final steps to complete the enzootic B. afzelii lifecycle and are included in the review. It is concluded that rodent density, rodent infection prevalence, and tick burden are the major factors affecting the development from larva to infected nymph and that these interact with each other. We suggest that the B. afzelii lifecycle is dependent on the aggregation of ticks among rodents, which is manipulated by the pathogen itself. Better understanding of the processes involved in the development and aggregation of ticks results in more precise estimates of the density of infected nymphs, and hence predictions of Lyme borreliosis risk.
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24.) Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector.
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Appl Environ Microbiol. 2017 Jan 17;83(3). pii: e02552-16. doi: 10.1128/AEM.02552-16. Print 2017 Feb 1.
Durand J1, Herrmann C2, Genné D3, Sarr A3, Gern L2, Voordouw MJ3.
Author information
1
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland jonas.durand@unine.ch.
2
Laboratory of Eco-Epidemiology of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
3
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Neuchâtel, Switzerland.
Abstract
Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens. Previous studies have mainly focused on interactions between pathogen strains in the vertebrate host, but little is known about what happens in the arthropod vector. Borrelia afzelii and Borrelia garinii are two species of spirochete bacteria that cause Lyme borreliosis in Europe and that share a tick vector, Ixodes ricinus Each of these two tick-borne pathogens consists of multiple strains that are often differentiated using the highly polymorphic ospC gene. For each Borrelia species, we studied the frequencies and abundances of the ospC strains in a wild population of I. ricinus ticks that had been sampled from the same field site over a period of 3 years. We used quantitative PCR (qPCR) and 454 sequencing to estimate the spirochete load and the strain diversity within each tick. For B. afzelii, there was a negative relationship between the two most common ospC strains, suggesting the presence of competitive interactions in the vertebrate host and possibly the tick vector. The flat relationship between total spirochete abundance and strain richness in the nymphal tick indicates that the mean abundance per strain decreases as the number of strains in the tick increases. Strains with the highest spirochete load in the nymphal tick were the most common strains in the tick population. The spirochete abundance in the nymphal tick appears to be an important life history trait that explains why some strains are more common than others in nature.
IMPORTANCE:
Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere and is caused by spirochete bacteria that belong to the Borrelia burgdorferi sensu lato species complex. These tick-borne pathogens are transmitted among vertebrate hosts by hard ticks of the genus Ixodes Each Borrelia species can be further subdivided into genetically distinct strains. Multiple-strain infections are common in both the vertebrate host and the tick vector and can result in competitive interactions. To date, few studies on multiple-strain vector-borne pathogens have investigated patterns of cooccurrence and abundance in the arthropod vector. We demonstrate that the abundance of a given strain in the tick vector is negatively affected by the presence of coinfecting strains. In addition, our study suggests that the spirochete abundance in the tick is an important life history trait that can explain why some strains are more common in nature than others.
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25.) Inefficient co-feeding transmission of Borrelia afzelii in two common European songbirds.
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Sci Rep. 2017 Jan 5;7:39596. doi: 10.1038/srep39596.
Heylen DJ1, Sprong H2, Krawczyk A2, Van Houtte N1, Genné D3, Gomez-Chamorro A3, van Oers K4, Voordouw MJ3.
Author information
1
Evolutionary Ecology Group, Department of Biology, University of Antwerp, Belgium.
2
Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
3
Laboratory of Ecology and Evolution of Parasites, Institute of Biology, University of Neuchâtel, Switzerland.
4
Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands.
Abstract
The spirochete bacterium Borrelia afzelii is the most common cause of Lyme borreliosis in Europe. This tick-borne pathogen can establish systemic infections in rodents but not in birds. However, several field studies have recovered larval Ixodes ricinus ticks infected with B. afzelii from songbirds suggesting successful transmission of B. afzelii. We reviewed the literature to determine which songbird species were the most frequent carriers of B. afzelii-infected I. ricinus larvae and nymphs. We tested experimentally whether B. afzelii is capable of co-feeding transmission on two common European bird species, the blackbird (Turdus merula) and the great tit (Parus major). For each bird species, four naïve individuals were infested with B. afzelii-infected I. ricinus nymphal ticks and pathogen-free larval ticks. None of the co-feeding larvae tested positive for B. afzelii in blackbirds, but a low percentage of infected larvae (3.33%) was observed in great tits. Transstadial transmission of B. afzelii DNA from the engorged nymphs to the adult ticks was observed in both bird species. However, BSK culture found that these spirochetes were not viable. Our study suggests that co-feeding transmission of B. afzelii is not efficient in these two songbird species.
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26.) Borrelia sp. phylogenetically different from Lyme disease- and relapsing fever-related Borrelia spp. in Amblyomma varanense from Python reticulatus.
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Parasit Vectors. 2016 Jun 24;9(1):359. doi: 10.1186/s13071-016-1629-8.
Trinachartvanit W1, Hirunkanokpun S2, Sudsangiem R1, Lijuan W3, Boonkusol D4, Baimai V1,5, Ahantarig A6,7.
Author information
1
Biodiversity Research Cluster, Department of Biology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand.
2
Department of Biology, Faculty of Science, Ramkhamhaeng University, Ramkhamhaeng Road, Bangkok, 10240, Thailand.
3
Department of Science Education, Faculty of Science and Technology, Thepsatri Rajabhat University, Maung, Lopburi, 15000, Thailand.
4
Department of Biology, Faculty of Science and Technology, Thepsatri Rajabhat University, Maung, Lopburi, 15000, Thailand.
5
Center of Excellence for Vectors and Vector-Borne Diseases, Faculty of Science, Mahidol University at Salaya, Phutthamonthon 4 Road, Nakhon Pathom, 73170, Thailand.
6
Biodiversity Research Cluster, Department of Biology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand. arunee.aha@mahidol.ac.th.
7
Center of Excellence for Vectors and Vector-Borne Diseases, Faculty of Science, Mahidol University at Salaya, Phutthamonthon 4 Road, Nakhon Pathom, 73170, Thailand. arunee.aha@mahidol.ac.th.
Abstract
BACKGROUND:
Species of the genus Borrelia are causative agents of Lyme disease and relapsing fever. Lyme disease is the most commonly reported vector-borne disease in the northern hemisphere. However, in some parts of the world Lyme borreliosis and relapsing fever may be caused by novel Borrelia genotypes. Herein, we report the presence of a Borrelia sp. in an Amblyomma varanense collected from Python reticulatus.
METHODS:
Ticks were collected from snakes, identified to species level and examined by PCR for the presence of Borrelia spp. flaB and 16S rRNA genes. Phylogenetic trees were constructed using the neighbour-joining method.
RESULTS:
Three A. varanense ticks collected from P. reticulatus were positive for a unique Borrelia sp., which was phylogenetically divergent from both Lyme disease- and relapsing fever-associated Borrelia spp.
CONCLUSION:
The results of this study suggest for the first time that there is a Borrelia sp. in A. varanense tick in the snake P. reticulatus that might be novel.
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27.) [Ixodes ricinus, transmitted diseases and reservoirs].
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Parassitologia. 2004 Jun;46(1-2):119-22.
[Article in Italian]
Rizzoli A1, Rosà R, Mantelli B, Pecchioli E, Hauffe H, Tagliapietra V, Beninati T, Neteler M, Genchi C.
Author information
1
Centro di Ecologia Alpina, Viote del Monte Bondone, 38040, Trento, Italy.
Abstract
The tick Ixodes ricinus has been recorded in most Italian regions especially in thermo-mesophilous woods and shrubby habitats where the relative humidity allow the tick to complete its 3 year developmental cycle, as predicted for the European climatic ranges. This tick acts both as vector and reservoir for a series of wildlife zoonotic pathogens, especially the agents of Lyme diseases, Tick borne encephalitis and Human Granulocytic Ehrlichiosis, which are emerging in most of Europe. To assess the spatial distribution of these pathogens and the infection risk for humans and animals within the territory of the Province of Trento, we carried out a long term study using a combination of eco-epidemiological surveys and mathematical modelling. An extensive tick collection with a GIS based habitat suitability analysis allowed us to identify the areas where tick occurs at various density. To identify the areas with higher infection risk, we estimated the values of R0 for Borrelia burgdorferi s.l., TBE virus and Anaplasma phagocytophila under different ecological conditions. We assessed the infection prevalence in the vector and in the wildlife reservoir species that play a central role in the persistence of these infections, ie the small mammals A. flavicollis and C. glareolus. We also considered the double effect of roe deer (Capreolus capreolus) which act as reservoir for A. phagocytophila but is an incompetent host for B. burgdorferi and TBE virus, thus reducing the infection prevalence in ticks of these last two pathogens. Infection prevalence with B. burgdorferi and A. phagocytophila in the vector was assessed by PCR screening 1212 I. ricinus nymphs collected by dragging in six main study areas during 2002. The mean infection prevalence recorded was 1.32% for B. burgdorferi s.l. and 9.84% for A. phagocytophila. Infection prevalence in nymphs with TBE virus, as assessed in a previous study was 0.03%. Infection prevalence in rodents was assessed by screening (with ELISA and PCR) tissues and blood samples collected from 367 rodent individuals trapped extensively during 2002 within 6 main study areas. A. flavicollis (N=238) was found to be infected with all three pathogens investigated, with infection prevalence ranging from 3.3% for TBE virus to 11.7% for A. phagocytophila, and 16.6% with B. burgdorferi s.l. C. glareolus (N=108) showed an infection prevalence of 6.5% with A. phagocytophila and 12.7% with B. burgdorferi s.l., while no individuals were infected with TBE virus. We also screened 98 spleen samples collected from roe deer with PCR, resulting in a mean prevalence of infection with A. phagocytophila of 19.8%. Using a deterministic model we explored the condition for diseases persistence under different rodent and roe deer densities. R0 values resulted largely above 1 for B. burgdorferi s.l. in the vast majority of the areas classified as suitable for I. ricinus occurrence in Trentino, while the condition for TBE persistence appeared to be more restricted by a combination of climatic condition and host densities.
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28.) ["Reversible" dementia in 2011].
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Geriatr Psychol Neuropsychiatr Vieil. 2011 Jun;9(2):211-25. doi: 10.1684/pnv.2011.0274.
[Article in French]
Michel JM1, Sellal F.
Author information
1
CMRR de Strasbourg-ColmarCMRR de Strasbourg-ColmarCMRR de Strasbourg-Colmar. jeanmarc.michel@ch-colmar.fr
Abstract
Reversible dementias are rare and account for approximately 1.5% of all dementias. The most frequent etiology is represented by neurosurgical causes such as benign tumours, adult chronic hydrocephalus (so-called « normal pressure » hydrocephalus) or subdural hematoma, which are easily revealed by neuroimaging. Systematic ancillary investigations aimed at detecting an infectious disease (syphilis, HIV infection, Lyme neuroborreliosis or, more rarely, Whipple disease), an endocrine aetiology or a vitamin deficiency are rarely contributory, but remain relevant since these dementias could be reversible. Discovering a reversible cause of dementia does not always allow full recovery after treatment. However, systematic ancillary investigations can identify and treat concomitant reversible conditions, which contribute to worsening the main clinical condition in nearly 25% of dementia cases.
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29.) Chronic inflammation and amyloidogenesis in Alzheimer's disease -- role of Spirochetes.
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J Alzheimers Dis. 2008 May;13(4):381-91.
Miklossy J1.
Author information
1
University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada. judithmiklossy@bluewin.ch
Abstract
Alzheimer's disease (AD) is associated with dementia, brain atrophy and the aggregation and accumulation of a cortical amyloid-beta peptide (Abeta). Chronic bacterial infections are frequently associated with amyloid deposition. It had been known from a century that the spirochete Treponema pallidum can cause dementia in the atrophic form of general paresis. It is noteworthy that the pathological hallmarks of this atrophic form are similar to those of AD. Recent observations showed that bacteria, including spirochetes contain amyloidogenic proteins and also that Abeta deposition and tau phosphorylation can be induced in or in vivo following exposure to bacteria or LPS. Bacteria or their poorly degradable debris are powerful inflammatory cytokine inducers, activate complement, affect vascular permeability, generate nitric oxide and free radicals, induce apoptosis and are amyloidogenic. All these processes are involved in the pathogenesis of AD. Old and new observations, reviewed here, indicate that to consider the possibility that bacteria, including several types of spirochetes highly prevalent in the population at large or their persisting debris may initiate cascade of events leading to chronic inflammation and amyloid deposition in AD is important, as appropriate antibacterial and antiinflammatory therapy would be available to prevent dementia.
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30.) Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
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J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 673-81.
Miklossy J1, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.
Author information
1
University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland. judmik@telus.net
Abstract
The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.
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31.) Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes.
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Neurobiol Aging. 2006 Feb;27(2):228-36.
Miklossy J1, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K.
Author information
1
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3. judmik@telus.net
Abstract
The pathological hallmarks of Alzheimer's disease (AD) consist of beta-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of beta-amyloid precursor protein (AbetaPP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.
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32.) Alzheimer's disease--a spirochetosis?
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Neuroreport. 1993 Jul;4(7):841-8.
Miklossy J1.
Author information
1
Division of Neuropathology, University of Lausanne, Switzerland.
Abstract
The aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (beta A4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the beta amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the beta amyloid deposited in the AD brain.
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33.) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
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J Neuroinflammation. 2011 Aug 4;8:90. doi: 10.1186/1742-2094-8-90.
Miklossy J1.
Author information
1
International Alzheimer Research Center, Prevention Alzheimer Foundation, Martigny-Combe, Switzerland. judithmiklossy@bluewin.ch
Abstract
It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.
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34.) Link between chronic bacterial inflammation and Alzheimer disease.
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CNS Neurol Disord Drug Targets. 2014;13(7):1140-7.
Bibi F, Yasir M, Sohrab SS, Azhar EI, Al-Qahtani MH, Abuzenadah AM, Kamal MA, Naseer MI1.
Author information
1
Center of Excellence in Genomic Medicine and Research (CEGMR), King Abdulaziz University Jeddah 21589, Saudi Arabia. mimrannaseer@yahoo.com.
Abstract
Alzheimer's disease (AD) is a degenerative disease of brain that is associated with dementia, brain atrophy, accumulation of hyperphosphorylated tau protein and amyloid-beta peptide in hippocampus and cortex region of the brain. The development of AD is a multifactorial process that may also involve infection with bacterial pathogens. Recent studies suggest that bacteria including spirochetes have the potential to initiate cascade of events, leading to inflammatory condition of the central nervous system. Bacteria and spirochetes are activators of proinflammatory cytokines, generate free radicals, nitric oxide and further induction of apoptosis. Infection with these microbes may be considered as a risk factor for pathophysiology of AD or to cognitive changes. Recent studies have revealed that exposure to these microorganisms induces Aβ accumulation and tau protein phosphorylation, and chronic infections with these pathogenic bacteria can possibly contribute to progression of AD. In this article, we update and review the role of bacteria in the pathogenesis of AD resulting from initiation of cascade events in chronic inflammations and amyloidogenesis. Controlling these chronic infections with antibacterial or anti-inflammatory drugs will allow preventing inflammation, a risk factor for AD.
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35.) Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?
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Alzheimers Dement. 2009 Jul;5(4):348-60. doi: 10.1016/j.jalz.2008.12.001.
Honjo K1, van Reekum R, Verhoeff NP.
Author information
1
L.C. Campbell Cognitive Neurology Research Unit, Heart and Stroke Foundation Centre for Stroke Recovery, Section of Neurology, Department of Medicine, Sunnybrook Health Science Centre and University of Toronto, Toronto, Ontario, Canada.
Abstract
Infection with several important pathogens could constitute risk factors for cognitive impairment, dementia, and Alzheimer's disease (AD) in particular. This review summarizes the data related to infectious agents that appear to have a relationship with AD. Infections with herpes simplex virus type 1, picornavirus, Borna disease virus, Chlamydia pneumoniae, Helicobacter pylori, and spirochete were reported to contribute to the pathophysiology of AD or to cognitive changes. Based on these reports, it may be hypothesized that central nervous system or systemic infections may contribute to the pathogenesis or pathophysiology of AD, and chronic infection with several pathogens should be considered a risk factor for sporadic AD. If this hypothesis holds true, early intervention against infection may delay or even prevent the future development of AD.
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36.) Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.
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Harris SA1, Harris EA2.
Author information
1
St. Vincent Medical Group, Northside Internal Medicine, Indianapolis, IN, USA.
2
Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract
This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.
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37.) Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro.
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Antibiotics (Basel). 2017 Mar 22;6(1). pii: E10. doi: 10.3390/antibiotics6010010.
Feng J1, Zhang S2, Shi W3, Zhang Y4.
Author information
1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. jfeng16@jhu.edu.
2
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. szhang30@jhu.edu.
3
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. wshi3@jhu.edu.
4
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu.
Abstract
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug-containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
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38.) Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.
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Carris NW1, Pardo J2, Montero J3, Shaeer KM4.
Author information
1
Department of Pharmacotherapeutics and Clinical Research , University of South Florida College of Pharmacy ; Departments of Family Medicine.
2
Department of Pharmacy , North Florida/South Georgia Veterans Health System , Gainesville.
3
Internal Medicine , University of South Florida, Morsani College of Medicine , Tampa.
4
Department of Pharmacotherapeutics and Clinical Research , University of South Florida College of Pharmacy ; Internal Medicine , University of South Florida, Morsani College of Medicine , Tampa.
Abstract
Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.
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39.) Ineffectiveness of tigecycline against persistent Borrelia burgdorferi.
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Antimicrob Agents Chemother. 2010 Feb;54(2):643-51. doi: 10.1128/AAC.00788-09. Epub 2009 Dec 7.
Barthold SW1, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.
Author information
1
Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. swbarthold@ucdavis.edu
Abstract
The effectiveness of a new first-in-class antibiotic, tigecycline (glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of tigecycline, saline (negative-effect controls), or a previously published regimen of ceftriaxone (positive-effect controls). Infection status was assessed at 3 months after treatment by culture, quantitative ospA real-time PCR, and subcutaneous transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with antibiotics were ospA PCR positive, although the DNA marker load was markedly decreased compared to that in saline-treated mice. Antibiotic treatment during the early stage of infection appeared to be more effective than treatment that began during later stages of infection. The viability of noncultivable spirochetes in antibiotic-treated mice (demonstrable by PCR) was confirmed by transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from antibiotic-treated mice revealed RNA transcription of several B. burgdorferi genes. These results extended previous studies with ceftriaxone, indicating that antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.
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40.) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?
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Med Hypotheses. 2005;64(3):438-48.
Fritzsche M1.
Author information
1
Clinic for Internal and Geographical Medicine, Soodstrasse 13, 8134 Adliswil, Switzerland. markus.fritzsche@gmx.ch
Abstract
Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet. Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks. In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable. As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted. The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS. Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls. Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be large enough and preferably taken together in a multi-centre study
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41.) [Minocycline].
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Ann Dermatol Venereol. 2001 May;128(5):627-37.
[Article in French]
Bernier C1, Dréno B.
Author information
1
Clinique Dermatologique, Hôtel-Dieu, Place Alexis Ricordeau, 44093 Nantes Cedex 1.
Abstract
Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treonema and Proprionibacterium acenes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.
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42.) Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis.
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Infection. 1996 Jan-Feb;24(1):69-72.
Breier F1, Kunz G, Klade H, Stanek G, Aberer E.
Author information
1
Universitätsklinik für Dermatologie, Wien, Austria.
Abstract
An open, randomized, prospective study was carried out to compare the clinical efficacy and safety of phenoxymethylpenicillin with that of minocycline in the treatment of erythema migrans. Sixty patients (minocycline 30, penicillin 30) were enrolled in the study. The two groups of patients were statistically homogeneous regarding age and sex distribution. IgG and IgM antibodies against Borrelia burgdorferi were determined by ELISA before and after treatment and 1 year thereafter. Thirty-nine patients completed the study. All these patients (penicillin 21, minocycline 18) who received a 21-day course of treatment were free of clinical symptoms of late Lyme borreliosis after 1 year. Serum antibodies against B. burgdorferi could be detected before treatment in 6/21 patients treated with penicillin and 3/18 patients treated with minocycline. After 1 year 8/39 patients were seropositive without any evidence of ongoing disease. In the remaining 21 patients treatment could not be completed with the initial antibiotic due to side effects (penicillin 9/30, minocycline 12/30). One patient, who stopped penicillin treatment at day 14 and one patient who stopped minocycline at day 4, developed fatigue and memory impairment within the observation period. A 3-week course of treatment with penicillin or minocycline is equally effective in treating patients with erythema migrans and preventing late symptoms of Lyme borreliosis.
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43.) Influence of tick and mammalian physiological temperatures on Borrelia burgdorferi biofilms.
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Microbiology. 2016 Nov;162(11):1984-1995. doi: 10.1099/mic.0.000380.
Shaikh S1, Timmaraju VA1, Torres JP1, Socarras KM1, Theophilus PA1, Sapi E1.
Author information
Abstract
The spirochaete bacterium Borrelia burgdorferisensu lato is the aetiologic agent of Lyme disease. Borrelia is transmitted to mammals through tick bite and is adapted to survive at tick and mammalian physiological temperatures. We have previously shown that B. burgdorferi can exist in different morphological forms, including the antibiotic-resistant biofilm form, in vitro and in vivo. B. burgdorferi forms aggregates in ticks as well as in humans, indicating potential of biofilm formation at both 23 and 37 °C. However, the role of various environmental factors that influence Borrelia biofilm formation remains unknown. In this study, we investigated the effect of tick (23 °C), mammalian physiological (37 °C) and standard in vitro culture (33 °C) temperatures with the objective of elucidating the effect of temperature on Borrelia biofilm phenotypes invitro using two B. burgdorferisensu stricto strains (B31 and 297). Our findings show increased biofilm quantity, biofilm size, exopolysaccharide content and enhanced adherence as well as reduced free spirochaetes at 37 °C for both strains, when compared to growth at 23 and 33 °C. There were no significant variations in the biofilm nano-topography and the type of extracellular polymeric substance in Borrelia biofilms formed at all three temperatures. Significant variations in extracellular DNA content were observed in the biofilms of both strains cultured at the three temperatures. Our results indicate that temperature is an important regulator of Borrelia biofilm development, and that the mammalian physiological temperature favours increased biofilm formation in vitro compared to tick physiological temperature and in vitro culture temperature.
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44.) Cimetidine as a novel adjunctive treatment for early stage Lyme disease.
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Med Hypotheses. 2016 Apr 9. pii: S0306-9877(16)30007-X. doi: 10.1016/j.mehy.2016.03.015. [Epub ahead of print]
Shemenski J1.
Author information
1
D'Youville College, 320 Porter ave, Buffalo, NY 14201, United States. Electronic address: Shemej25@dyc.edu.
Abstract
Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease.
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45.) Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas.
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Eur J Microbiol Immunol (Bp). 2016 Feb 9;6(1):9-24. doi: 10.1556/1886.2015.00049. eCollection 2016.
Sapi E1, Balasubramanian K1, Poruri A1, Maghsoudlou JS1, Socarras KM1, Timmaraju AV1, Filush KR1, Gupta K1, Shaikh S1, Theophilus PA1, Luecke DF1, MacDonald A1, Zelger B2.
Author information
1
Department of Biology and Environmental Science, University of New Haven , West Haven, CT 06516, USA.
2
Department of Dermatology and Venereology, Medical University Innsbruck , Innsbruck, Austria.
Abstract
Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues.
