Lähettäjä: Soijuv Lähetetty: 5.1.2006 10:11
Infektiotauteihin erikoistunut amerikkalainen lääkäri Sam Donta, joka on tutkinut ja hoitanut paljon borrelioosiin sairastuneita, kirjoitti jokin aika sitten yhdistyksemme jäsenelle näkemyksensä kroonisen borrelioosin hoidosta. Hänen hoitoprotokollastaan kysellään toistuvasti joten laitan sen uudelleen sivuillemme.
Lopussa on myös kaksi tutkimusta. Toisessa on todettu lyhyen antibioottihoidon olleen tuloksettoman. Asiaa seurattiin seerumin sytokiiniarvoista. Toisessa pitkilläkään antibioottihoidoilla ei välttämättä ole saavutettu toivottuja tuloksia. Joten borrelioosin tuloksekas hoito on edelleen lopullista ratkaisua vailla.
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S. Donta: Kroonisen borrelioosin hoito:
1. Klaritromysiini 500 mg x 2 + hydroksiklorokiini 200 mg x 2 ruoan yhteydessä.
2. Tetrasykliini (ei doksisykliini) 500 mg x 3. Otetaan 20 min ennen aterioita tai 750 mg x 2 ennen aamiaista ja illallista.
Hoitoa tulee jatkaa vähintään 3 kk ja mieluummin 4 - 7 kk jotta saavutettaisiin paras mahdollinen hoitotulos. Hoidon voi aloittaa esim. ykköshoitovaihtoehdolla ja vaihtaa myöhemmin kakkosvaihtoehtoon. Hoidon aikana ei tule käyttää B- tai C-vitamiineja.
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Alkuperäinen sähköpostiviesti:
For treatment of chronic Lyme disease, I'd recommend one of two following regimens:
1-combination of clarithromycin-500mg and hydroxychloroquine-200mg take together twice daily with food, or
2-tetracycline (not doxycycline)-1500mg/day, taken as 500mg 3x/day 20min before meals or 750mg twice a day 20min before breakfast & supper.Regardless of the regimen, you need to take it for at least 3 months, and preferably for 4-7 months to get the full benefit.
You can start with regimen #1, then change to tetracycline.
You should not take any supplemental B or C vitamins during the treatment process.
I've attached copies of two articles that could be of help to your doctor.
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Seerumin sytokiiniarvoja seuraamalla puolalaiset tutkijat tulivat siihen tulokseen ettei lyhyt antibioottihoito ole riittävä hoitoprotokolla borrelioosissa. Varsinainen artikkeli on puolaksi joten en tiedä oliko kyseessä borrelioosin varhais- vai krooninen vaihe:
Effect of antibiotic therapy on levels of proinflammatory cytokines: interleukin IL-1, IL-6 and tumor necrosis factor TNF-alpha in serum of patients with Lyme borreliosis]Wiad Lek. 2002;55(5-6):276-81
[Article in Polish]
Kondrusik M, Swierzbinska R, Zajkowska JM, Pancewicz SA, Grygorczuk S, Hermanowska-Szpakowicz T.
Kliniki Chorob Zakaznych i Neuroinfekcji Akademii Medycznej w Bialymstoku.
We estimated serum concentrations of cytokines: IL-1, IL-6, TNF-alpha in patients with diagnosed Lyme disease treated for 14 days with antibiotics. The detection of proinflammatory cytokines was performed by ELISA tests. The examination was carried out before and after the treatment. The comparison with control group stated statistically significant higher concentration of IL-1, IL-6 and TNF-alpha before and after the treatment. Comparing the concentrations of cytokines after treatment with control group showed normalization only in a few cases. In the majority of cases serum cytokines concentrations remained significantly higher. That is why we conclude that 14-day-therapy with antibiotic in patients with Lyme disease may not be sufficient.
PMID: 12235693 [PubMed - indexed for MEDLINE]
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Seuraavan tutkimuksen mukaan (80 potilasta) potilailla esiintyi krooninen infektio pitkistä antibioottihoidoista huolimatta (keskimäärin 13 kk). "Sinulla ei ole enää borrelioosia sillä olet saanut riittäväksi katsotut hoidot" - lause lienee tästä huolimatta useimmille tuttu.
13th International Scientific Conference on Lyme Disease & Other Tick-Borne Disorders
Emphasis: Pediatrics & New Research
March 24-26, 2000 Hartford Marriott Farmington, CT, USA
Chronic Persistent Lyme Borreliosis: PCR Evidence of Chronic Infection Despite Extended Antibiotic Therapy?A Retrospective Review
Dr. Richard Horowitz
Background:
B. burgdorferi has been proven by PCR analysis to establish a persistent infection in the mammalian host (Straubinger, R. Persistence of B. burgdorferi in experimentally infected dogs after antibiotic treatment. J.Clin.Microbiol.1997 Jan; 35(l): 111-116). Use of PCR assays to monitor the clearance of B. burgdorferi DNA from blood following antibiotic therapy has also been described (Manak et al, Abstract, IX Annual Intl Conference on Lyme Borreliosis, April 1996). This report describes serum PCR positivity in a cohort of chronic Lyme patients despite prolonged treatment with multiple antibiotic regimens.
Methodology:
80 patients with Lyme Borreliosis and/or Ehrlichiosis and Babesiosis were treated with multiple courses of antibiotics, including tetracycline derivatives (doxycycline, minocycline, tetracycline HCL), macrolides (azithromycin, clarithromycin) penicillins (amoxicillin, IM benzathine penicillin), cephalosporins (cefuroxime axetil, cefixime, IV ceftriaxone, IV cefotaxime) and metronidazole. These drugs were used alone or in combination, with hydroxychloroquine added to tetracycline or macrolide antibiotics in select patients. Patients with chronic persistent symptomatology post therapy had serum PCR testing done through MDL Laboratories in New Jersey. Between one and five specimens were sent on each patient, with serial specimens generally on consecutive days. Two sets of primers are utilized for the PCR reaction for each specimen: (I) the SL primers amplify a region of the B. burgdorferi senso stricto B31 OspA sequence; (II) The Ly primers amplify the region of the Ly1 chromosomal gene.
Results & Conclusion:
Patients received an average of 13 months of treatment (range: 1 month-53 months) with the longest course reserved for a patient with a severe chronic relapsing encephalopathy. All 80 charts reviewed showed serum PCR positivity for B. burgdorferi despite extended courses of antibiotics, and serial PCRs were frequently necessary to prove ongoing infection. Straubinger illustrated in the dog model that antibiotics decreased the total number of organisms in tissue samples, but did not eliminate the infection (Abstract, 12th Intl. Lyme Conference, April 1999), and others have shown persistent infection by PCR and culture even in patients with negative standard blood tests for Lyme (Bayer, et al: Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms: A PCR study of 97 cases. Infection, 1996 Sep, 24: 5, 347-353; OKSI et al: Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med 1999 Jun; 31(3): 225-232). This retrospective study highlights several points in chronic Lyme disease treatment: No single antibiotic or combination of antibiotics used was able to completely eradicate the infection, although significant clinical improvement was seen with chronic antibiotic therapy. Overlap of clinical syndromes may occur with Lyme disease and Babesiosis, and consecutive serial PCR specimens (5) for B burgdorferi and B microti are often useful to differentiate between these 2 disease states in patients with chronic persistent symptomatology.
DONTA: KROONISEN BORRELIOOSIN HOITO
Valvojat: Jatta1001, Borrelioosiyhdistys, Bb
DONTA: KROONISEN BORRELIOOSIN HOITO
Viimeksi muokannut Bb, La Huhti 10, 2010 13:48. Yhteensä muokattu 2 kertaa.
Lähettäjä: Soijuv Lähetetty: 5.1.2006 10:54
Dontan artikkeleita:
Ensimmäinen artikkeli: Artikkelissa Donta puhuu mm IgM vasta-aineen jatkuvasta positiivisuudesta kroonisessa borrelioosissa sekä ehdottaa antibiooteiksi tetrasykliinejä ja makrolidejä yms. Krooninen borrelioosi on hänen mukaansa tosiasia eikä spekuloinnin aihe.
Toinen artikkeli: Dontan mukaan borrelioosin oireet aiheuttaa suureksi osaksi toksiini Bbtox1. Uusi menetelmä auttaisi sekä borrelioosin diagnosoinnissa että sen hoidossa.
The Existence of Chronic Lyme Disease
Current Treatment Options in Infectious Diseases 2001, 3:261?262
Sam T. Donta, MD
Address Infectious Diseases, Biomolecular Medicine, Lyme Disease Unit, Boston City Veterans Affairs Medical Centers 650 Albany Street, Boston, MA 02215, USA. E-mail: sadonta@bmc.org
Patients who become infected with Borrelia burgdorferi may have acute signs of infection, be asymptomatic, or develop manifestations of the disease.
Some of the common consequences of infection include neurologic signs and symptoms such as headache, meningitis, and Bell?s palsy; musculoskeletal involvement in the form of myalgias and arthralgias, with or without arthritis; fatigue; and a chronic multisymptom disorder.
Whereas certain manifestations of Lyme disease are relatively easy to recognize, such as erythema migrans, Bell?s palsy, bradycardia with heart block, and arthritis (especially monoarticular or oligoarticular), recognizing the chronic multisymptom form of the disease has created more difficulties.
Chronic Lyme disease is indistinguishable from other multisymptom disorders that are termed chronic fatigue, fibromyalgia, multiple chemical sensitivity, and Gulf War illness. These are terms that describe the principal symptoms or epidemiologic association, but not the underlying cause. All these disorders share the major triad of symptoms: fatigue, muscle/joint pains or stiffness, and neurocognitive or neuropsychiatric dysfunction. There are additional symptoms, probably neurologically related, such as paresthesia, tremor, palpitation, dysequilibrium, gastrointestinal disturbances, and urinary frequency. Lyme disease is a common cause of fibromyalgia and chronic fatigue, especially in endemic areas, and should serve as a model for other potential causes of chronic fatigue and fibromyalgia. The epidemiologic studies of Shadick et al. [1], Asch et al. [2], and our institute [3?6] have established that well-documented cases of Lyme disease, including those in patients with known tick bites and typical rashes, may progress to the chronic multisymptom form of this disease, even if treated.
There have been attempts to distinguish late Lyme disease from chronic Lyme disease, or to deny the existence of chronic disease, claiming that the various symptoms are part of daily life [7]. Late disease has been said to be that of limited involvement of the joints (in the form of an oligoarticular arthritis) or the neurologic system (in the form of meningitis, Bell?s palsy, radiculopathy, or encephalopathy). In addition, diagnosis and treatment of late disease is relatively easy and straightforward. This appears to be the case in many patients who have prominent serologic responses, especially IgG, to many of the antigens of B. burgdorferi, and who appear to respond well to limited courses of antibiotics.
In contrast, chronic disease appears to generate less robust immunologic responses and requires longer courses of antibiotics to control or cure the illness [3?6]. Typical of most cases of chronic disease, there are IgM responses with limited IgG responses. The IgM responses to highly specific proteins of B. burgdorferi, such as 23kd (OspC), 31 kd (OspA), 34 kd (OspB), 35 kd, 37 kd, 39 kd, and 83/93 kd, and the most commonly seen response to the 41-kd flagellar protein, indicate infection by B. burgdorferi and are frequently signs of disease activity. The IgM reactivity is not unique to chronic Lyme disease; there are examples of other infections that retain IgM reactivity concurrent with active disease (eg, hepatitis B) or express reactivation of disease (eg, toxoplasmosis, cytomegalovirus).
With successful treatment, the IgM responses in chronic Lyme disease dissipate, sometimes with seroconversion to IgG reactivity [3].The mechanisms underlying the persistent IgM reactivity and limited IgG reactivity need to be determined but may involve a failure to switch from IgM to IgG responses. Treatment of the chronic disease has not been optimized, but much has been learned through trial and error. Symptom-oriented treatments such as amitryptilline, exercise therapies, and anti-inflammatory agents appear to be of limited value, similar to outcomes seen in chronic fatigue and fibromyalgia. The best treatmentsthus far appear to be antibiotics capable of intracellularpenetration, such as the tetracyclines and the macrolides. With the tetracyclines, the parent compound appears to be much more effective than doxycycline or minocycline, possibly because of the higher dose and less proteinbinding for tetracyline. The limited clinical activity of macrolide antibiotics, despite excellent in vitro sensitivities and intracellular penetration, appears to be greatly enhanced with the concomitant use of lysosomotropic agents (especially hydroxychloroquine) that alkalinize intracellular acidic endosomes [8]. The concomitant use presumably enhances macrolide antibiotic activity, which is otherwise limited at an acid pH [4]. These clinicalobservations also support the hypothesis that the borreliapersist intracellularly in an acidic environment. With tetracycline or augmented macrolide therapies, the duration of therapy appears to be an important determinant of outcome. If chronic disease is present for morethan 1 to 3 years, it appears that 12 to 18 months of treatment is needed to cure or control the disease, with longer duration of illness requiring longer courses of therapy. Some patients with long-term chronic disease appear to have limited or no response to treatment, the reasons for which are unknown. The need for long courses of treatment is not unique to Lyme disease. Other chronic infections such as tuberculosis, leprosy, some fungal infections, and Q fever may require months to years of antibiotic therapy for adequate resolution or control of the disease.
There are more questions than answers for chronic Lyme disease. The existence of the disease should no longer be a question because the results of animal studies support the existence of persisting or relapsing infection [9?11]. The key questions that need to be addressed involve the mechanisms underlying the disease, how best to diagnose and distinguish the disease from other chronic multisymptom disorders, and how best to manage and treat the disease.
Title: Prevention, diagnosis and treatment of lyme disease
Abstract
The present invention provides compositions and methods related to Borrelia burgdorferi toxin and antitoxin preparations. In particular, the present invention provides methods and compositions for the diagnosis of Lyme disease, as well as for use in treating subjects infected with B. burgdorferi through passive immunization, and vaccine development.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides compositions and methods related to Borrelia burgdorferi toxins. In particular, the present invention provides methods and compositions for the diagnosis, treatment and prevention of Lyme disease and/or Syphilis.
The present invention provides significant advantages and improvements over existing methods, devices, and materials related to Lyme disease. For example, as indicated above, the diagnosis of Lyme disease is often hampered by the absence of reliable tests. In addition, after initial skin infection, cultures for B. burgdorferi are rarely positive. PCR-DNA tests for OspA and other gene determinants are also rarely positive with blood, urine and spinal fluid. Furthermore, serologic tests are generally unreliable (Donta, et al., Clin. Infect. Dis., 25:552-555 (1997)). ELISA and Western blot immunoanalyses are likewise unreliable indicators of current or past infection. Thus, new tests, such as those of the present invention provide important methods and compositions for improving the diagnostic accuracy, treatment, and prevention of Lyme disease.
The compositions and methods of the present invention provide means to prevent Lyme disease through vaccine development and utilization, as well as diagnose Lyme disease in subjects suspected of being exposed to B. burgdorferi. In particular, the present invention provides the full-length sequence of a B. burgdorferi toxin, a toxin that has not been previously identified. While an understanding of the mechanism is not necessary in order to make or use the present invention, it is contemplated that this toxin may play a role in the pathogenesis of Lyme disease. Furthermore, the isolation and purification of the toxin provides methods and compositions for preventing Lyme disease through passive antibody therapy. For example, it is contemplated that the Bbtox1 of the present invention will find use in development of antitoxins suitable for use in approaches to treat Lyme disease.
http://www.pharmcast.com/Patents100/Yr2 ... 03/6667038
_Lyme122303.htm Koko patenttihakemus
Dontan artikkeleita:
Ensimmäinen artikkeli: Artikkelissa Donta puhuu mm IgM vasta-aineen jatkuvasta positiivisuudesta kroonisessa borrelioosissa sekä ehdottaa antibiooteiksi tetrasykliinejä ja makrolidejä yms. Krooninen borrelioosi on hänen mukaansa tosiasia eikä spekuloinnin aihe.
Toinen artikkeli: Dontan mukaan borrelioosin oireet aiheuttaa suureksi osaksi toksiini Bbtox1. Uusi menetelmä auttaisi sekä borrelioosin diagnosoinnissa että sen hoidossa.
The Existence of Chronic Lyme Disease
Current Treatment Options in Infectious Diseases 2001, 3:261?262
Sam T. Donta, MD
Address Infectious Diseases, Biomolecular Medicine, Lyme Disease Unit, Boston City Veterans Affairs Medical Centers 650 Albany Street, Boston, MA 02215, USA. E-mail: sadonta@bmc.org
Patients who become infected with Borrelia burgdorferi may have acute signs of infection, be asymptomatic, or develop manifestations of the disease.
Some of the common consequences of infection include neurologic signs and symptoms such as headache, meningitis, and Bell?s palsy; musculoskeletal involvement in the form of myalgias and arthralgias, with or without arthritis; fatigue; and a chronic multisymptom disorder.
Whereas certain manifestations of Lyme disease are relatively easy to recognize, such as erythema migrans, Bell?s palsy, bradycardia with heart block, and arthritis (especially monoarticular or oligoarticular), recognizing the chronic multisymptom form of the disease has created more difficulties.
Chronic Lyme disease is indistinguishable from other multisymptom disorders that are termed chronic fatigue, fibromyalgia, multiple chemical sensitivity, and Gulf War illness. These are terms that describe the principal symptoms or epidemiologic association, but not the underlying cause. All these disorders share the major triad of symptoms: fatigue, muscle/joint pains or stiffness, and neurocognitive or neuropsychiatric dysfunction. There are additional symptoms, probably neurologically related, such as paresthesia, tremor, palpitation, dysequilibrium, gastrointestinal disturbances, and urinary frequency. Lyme disease is a common cause of fibromyalgia and chronic fatigue, especially in endemic areas, and should serve as a model for other potential causes of chronic fatigue and fibromyalgia. The epidemiologic studies of Shadick et al. [1], Asch et al. [2], and our institute [3?6] have established that well-documented cases of Lyme disease, including those in patients with known tick bites and typical rashes, may progress to the chronic multisymptom form of this disease, even if treated.
There have been attempts to distinguish late Lyme disease from chronic Lyme disease, or to deny the existence of chronic disease, claiming that the various symptoms are part of daily life [7]. Late disease has been said to be that of limited involvement of the joints (in the form of an oligoarticular arthritis) or the neurologic system (in the form of meningitis, Bell?s palsy, radiculopathy, or encephalopathy). In addition, diagnosis and treatment of late disease is relatively easy and straightforward. This appears to be the case in many patients who have prominent serologic responses, especially IgG, to many of the antigens of B. burgdorferi, and who appear to respond well to limited courses of antibiotics.
In contrast, chronic disease appears to generate less robust immunologic responses and requires longer courses of antibiotics to control or cure the illness [3?6]. Typical of most cases of chronic disease, there are IgM responses with limited IgG responses. The IgM responses to highly specific proteins of B. burgdorferi, such as 23kd (OspC), 31 kd (OspA), 34 kd (OspB), 35 kd, 37 kd, 39 kd, and 83/93 kd, and the most commonly seen response to the 41-kd flagellar protein, indicate infection by B. burgdorferi and are frequently signs of disease activity. The IgM reactivity is not unique to chronic Lyme disease; there are examples of other infections that retain IgM reactivity concurrent with active disease (eg, hepatitis B) or express reactivation of disease (eg, toxoplasmosis, cytomegalovirus).
With successful treatment, the IgM responses in chronic Lyme disease dissipate, sometimes with seroconversion to IgG reactivity [3].The mechanisms underlying the persistent IgM reactivity and limited IgG reactivity need to be determined but may involve a failure to switch from IgM to IgG responses. Treatment of the chronic disease has not been optimized, but much has been learned through trial and error. Symptom-oriented treatments such as amitryptilline, exercise therapies, and anti-inflammatory agents appear to be of limited value, similar to outcomes seen in chronic fatigue and fibromyalgia. The best treatmentsthus far appear to be antibiotics capable of intracellularpenetration, such as the tetracyclines and the macrolides. With the tetracyclines, the parent compound appears to be much more effective than doxycycline or minocycline, possibly because of the higher dose and less proteinbinding for tetracyline. The limited clinical activity of macrolide antibiotics, despite excellent in vitro sensitivities and intracellular penetration, appears to be greatly enhanced with the concomitant use of lysosomotropic agents (especially hydroxychloroquine) that alkalinize intracellular acidic endosomes [8]. The concomitant use presumably enhances macrolide antibiotic activity, which is otherwise limited at an acid pH [4]. These clinicalobservations also support the hypothesis that the borreliapersist intracellularly in an acidic environment. With tetracycline or augmented macrolide therapies, the duration of therapy appears to be an important determinant of outcome. If chronic disease is present for morethan 1 to 3 years, it appears that 12 to 18 months of treatment is needed to cure or control the disease, with longer duration of illness requiring longer courses of therapy. Some patients with long-term chronic disease appear to have limited or no response to treatment, the reasons for which are unknown. The need for long courses of treatment is not unique to Lyme disease. Other chronic infections such as tuberculosis, leprosy, some fungal infections, and Q fever may require months to years of antibiotic therapy for adequate resolution or control of the disease.
There are more questions than answers for chronic Lyme disease. The existence of the disease should no longer be a question because the results of animal studies support the existence of persisting or relapsing infection [9?11]. The key questions that need to be addressed involve the mechanisms underlying the disease, how best to diagnose and distinguish the disease from other chronic multisymptom disorders, and how best to manage and treat the disease.
Title: Prevention, diagnosis and treatment of lyme disease
Abstract
The present invention provides compositions and methods related to Borrelia burgdorferi toxin and antitoxin preparations. In particular, the present invention provides methods and compositions for the diagnosis of Lyme disease, as well as for use in treating subjects infected with B. burgdorferi through passive immunization, and vaccine development.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides compositions and methods related to Borrelia burgdorferi toxins. In particular, the present invention provides methods and compositions for the diagnosis, treatment and prevention of Lyme disease and/or Syphilis.
The present invention provides significant advantages and improvements over existing methods, devices, and materials related to Lyme disease. For example, as indicated above, the diagnosis of Lyme disease is often hampered by the absence of reliable tests. In addition, after initial skin infection, cultures for B. burgdorferi are rarely positive. PCR-DNA tests for OspA and other gene determinants are also rarely positive with blood, urine and spinal fluid. Furthermore, serologic tests are generally unreliable (Donta, et al., Clin. Infect. Dis., 25:552-555 (1997)). ELISA and Western blot immunoanalyses are likewise unreliable indicators of current or past infection. Thus, new tests, such as those of the present invention provide important methods and compositions for improving the diagnostic accuracy, treatment, and prevention of Lyme disease.
The compositions and methods of the present invention provide means to prevent Lyme disease through vaccine development and utilization, as well as diagnose Lyme disease in subjects suspected of being exposed to B. burgdorferi. In particular, the present invention provides the full-length sequence of a B. burgdorferi toxin, a toxin that has not been previously identified. While an understanding of the mechanism is not necessary in order to make or use the present invention, it is contemplated that this toxin may play a role in the pathogenesis of Lyme disease. Furthermore, the isolation and purification of the toxin provides methods and compositions for preventing Lyme disease through passive antibody therapy. For example, it is contemplated that the Bbtox1 of the present invention will find use in development of antitoxins suitable for use in approaches to treat Lyme disease.
http://www.pharmcast.com/Patents100/Yr2 ... 03/6667038
_Lyme122303.htm Koko patenttihakemus