Lähettäjä: Soijuv Lähetetty: 31.12.2005 11:12
Artikkelin mukaan on selkeää tutkimuksellista näyttöä borrelioosioireiden esim. fatiikki, neurokognitiiviset vaikeudet ja luusto-lihaksistokivut, jatkumisesta vuosikausia antibioottihoidoista huolimatta.
http://ije.oxfordjournals.org/cgi/conte ... /34/6/1340
IJE Advance Access originally published online on July 22, 2005
International Journal of Epidemiology 2005 34(6):1340-1345; doi:10.1093/ije/dyi129
Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms
Victoria Cairns1 and Jon Godwin2
1 Consultant Statistician, Am Rothlauf 9, 61476 Kronberg, Germany
2 Clinical Trial Service Unit, University of Oxford, RDB, Roosevelt Drive, Oxford OX3 7LF, UK
* Corresponding author. E-mail: cairns@t-online.de
Background This meta-analysis compares the prevalence of fatigue, musculoskeletal pain, and neurocognitive difficulties in patients who have had Lyme borreliosis (LB) and control subjects without LB.
Methods Titles and abstracts in PubMed were reviewed for studies with data on the symptoms listed above that compared patients who had had LB with controls from the general population. Five studies with 504 patients and 530 controls were included in the meta-analysis.
Results The prevalence of symptoms was significantly higher in the LB patients, with P-values between <0.00001 and 0.007 for 8 of the 10 symptoms in the three categories listed above. The higher prevalence of certain neurocognitive symptoms but not others, in the same pattern as reported in the literature, is further confirmation of this syndrome. The pattern of symptoms appears to be different from that seen in fibromyalgia, depression, and chronic fatigue syndrome.
Conclusions This meta-analysis provides strong evidence that some patients with LB have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment.
KROONISET OIREET
Valvojat: Jatta1001, Borrelioosiyhdistys, Bb
KROONISET OIREET
Viimeksi muokannut Bb, La Maalis 07, 2009 12:50. Yhteensä muokattu 1 kertaa.
Lähettäjä: lare61 Lähetetty: 31.12.2005 15:07
Moi soile .ymmärsinkö oikein että tämä post-lyme syndroma on totta,ja kaikki muu valetta,eli ne kuuluisat jälkioireet ei enää lähde pois vaikka kuin söisi antipiotteja,taitaa artikkelin kirjoittaja olla sukua suomen oksille.HYVÄÄ UUTTA VUOTTA KAIKILLE.T.LARE
Moi soile .ymmärsinkö oikein että tämä post-lyme syndroma on totta,ja kaikki muu valetta,eli ne kuuluisat jälkioireet ei enää lähde pois vaikka kuin söisi antipiotteja,taitaa artikkelin kirjoittaja olla sukua suomen oksille.HYVÄÄ UUTTA VUOTTA KAIKILLE.T.LARE
Lähettäjä: Soijuv Lähetetty: 1.1.2006 13:48
Erilaisia tulkintoja ja tutkimuksia kroonisesta borrelioosista esiintyy niin paljon, että on välillä vaikea pysyä perässä. Näyttää siltä, että haluaa sitten selitellä miten päin tahansa tätä tautia niin aina löytyy jokin tutkimus joka tukee omia näkemyksiä. Eikä sillä asialla välttämättä ole mitään tekemistä totuuden kanssa. Vasta lukemalla satoja tutkimuksia ja tutustumalla tuhansiin potilaskertomuksiin ja mielellään vielä itse sairastamalla tätä tautia, on mahdollista päästä jonkinlaiseen kokonaisnäkemykseen kroonistuneen borrelioosin koko ongelmakentästä.
Tutkimuksessa tultiin siihen tulokseen että useiden potilaiden oireet jatkuvat mutta niiden syyhyn ei otettu kantaa eli siihen onko kysessä jatkuva borrelia bakteerin aiheuttama infektio, autoimmuunipohjaisia tulehduksia, useiden mikrobien aiheuttama infektio vai jotain muuta vai useiden tekijöiden summa. Vasta lukemalla koko tutkimus olisi todennäköisesti mahdollista selvittää lähemmin mikä oli tutkijoiden käsitys jatkuvien oireiden aiheuttajasta. Hyvä, että edes ilmaisivat, että antibioottihoito ei aina auta/poista oireita, jotta ne lukuisat lääkärit jotka pitävät pitkään jatkuneita oireita "psyykkisinä", tulisivat toisiin ajatuksiin.
Erilaisia tulkintoja ja tutkimuksia kroonisesta borrelioosista esiintyy niin paljon, että on välillä vaikea pysyä perässä. Näyttää siltä, että haluaa sitten selitellä miten päin tahansa tätä tautia niin aina löytyy jokin tutkimus joka tukee omia näkemyksiä. Eikä sillä asialla välttämättä ole mitään tekemistä totuuden kanssa. Vasta lukemalla satoja tutkimuksia ja tutustumalla tuhansiin potilaskertomuksiin ja mielellään vielä itse sairastamalla tätä tautia, on mahdollista päästä jonkinlaiseen kokonaisnäkemykseen kroonistuneen borrelioosin koko ongelmakentästä.
Tutkimuksessa tultiin siihen tulokseen että useiden potilaiden oireet jatkuvat mutta niiden syyhyn ei otettu kantaa eli siihen onko kysessä jatkuva borrelia bakteerin aiheuttama infektio, autoimmuunipohjaisia tulehduksia, useiden mikrobien aiheuttama infektio vai jotain muuta vai useiden tekijöiden summa. Vasta lukemalla koko tutkimus olisi todennäköisesti mahdollista selvittää lähemmin mikä oli tutkijoiden käsitys jatkuvien oireiden aiheuttajasta. Hyvä, että edes ilmaisivat, että antibioottihoito ei aina auta/poista oireita, jotta ne lukuisat lääkärit jotka pitävät pitkään jatkuneita oireita "psyykkisinä", tulisivat toisiin ajatuksiin.
Lähettäjä: Soijuv Lähetetty: 14.3.2006 14:03
Tässä yhdenlainen näkemys kroonisen borrelioosin hoidosta. Artikkelin mukaan antibioottihoitojen jälkeen jatkuvia oireita tulisi hoitaa oireidenmukaisesti eikä antibiooteilla.
Seerumin tai selkäydinnesteen vasta-aineiden mittausta ei kannata suorittaa koska ne ovat joka tapauksessa koholla.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Int J Med Microbiol. 2006 Mar 6;
Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients.
Pfister HW, Rupprecht TA.
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany.
The diagnostic criteria of active neuroborreliosis include inflammatory changes of the cerebrospinal fluid (CSF) and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production. Patients with neuroborreliosis are usually treated with intravenous ceftriaxone for 2-3 weeks. In case of allergy, doxycycline may be used. Treatment efficacy is detected by the improvement of the neurological symptoms and the normalization of the CSF pleocytosis. The measurement of serum and CSF antibodies is not suitable for follow-up, because they frequently persist.
Post-Lyme disease (PLD) syndrome is characterized by persistent complaints and symptoms after previous treatment for Lyme borreliosis, e.g., musculoskeletal or radicular pain, dysaesthesia, and neurocognitive symptoms that are often associated with fatigue. There is no formal definition of the PLD syndrome, and its pathogenesis is unclear. Recent controlled studies do not support the use of additional antibiotics in these patients, but recommend primarily symptomatic strategies.
PMID: 16524775 [PubMed - as supplied by publisher]
Tässä yhdenlainen näkemys kroonisen borrelioosin hoidosta. Artikkelin mukaan antibioottihoitojen jälkeen jatkuvia oireita tulisi hoitaa oireidenmukaisesti eikä antibiooteilla.
Seerumin tai selkäydinnesteen vasta-aineiden mittausta ei kannata suorittaa koska ne ovat joka tapauksessa koholla.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Int J Med Microbiol. 2006 Mar 6;
Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients.
Pfister HW, Rupprecht TA.
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany.
The diagnostic criteria of active neuroborreliosis include inflammatory changes of the cerebrospinal fluid (CSF) and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production. Patients with neuroborreliosis are usually treated with intravenous ceftriaxone for 2-3 weeks. In case of allergy, doxycycline may be used. Treatment efficacy is detected by the improvement of the neurological symptoms and the normalization of the CSF pleocytosis. The measurement of serum and CSF antibodies is not suitable for follow-up, because they frequently persist.
Post-Lyme disease (PLD) syndrome is characterized by persistent complaints and symptoms after previous treatment for Lyme borreliosis, e.g., musculoskeletal or radicular pain, dysaesthesia, and neurocognitive symptoms that are often associated with fatigue. There is no formal definition of the PLD syndrome, and its pathogenesis is unclear. Recent controlled studies do not support the use of additional antibiotics in these patients, but recommend primarily symptomatic strategies.
PMID: 16524775 [PubMed - as supplied by publisher]
Viimeksi muokannut Bb, La Maalis 07, 2009 12:51. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 15.3.2006 8:10
Edellinen tutkimus pidempänä versiona:
International Journal of Medical Microbiology
MINI-REVIEW
Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients
Hans-Walter Pfister, Tobias A. Rupprecht
Department of Neurology, Ludwig-Maximilians-University, Klinikum Großhadern, Marchioninistrasse 15,
D-81377 Munich, Germany
Abstract
The diagnostic criteria of active neuroborreliosis include inflammatory changes of the cerebrospinal fluid (CSF) and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production. Patients with neuroborreliosis are usually treated with intravenous ceftriaxone for 2?3 weeks. In case of allergy, doxycycline may be used. Treatment efficacy is detected by the improvement of the neurological symptoms and the normalization of the CSF pleocytosis. The measurement of serum and CSF antibodies is not suitable for follow-up, because they frequently persist. Post-Lyme disease (PLD) syndrome is characterized by persistent complaints and symptoms after previous treatment for Lyme borreliosis, e.g., musculoskeletal or radicular pain, dysaesthesia, and neurocognitive symptoms that are often associated with fatigue. There is no formal definition of the PLD syndrome, and its pathogenesis is unclear. Recent controlled studies do not support the use of additional antibiotics in these patients, but recommend primarily symptomatic strategies.
r 2006 Elsevier GmbH. All rights reserved.
Keywords: Borrelia burgdorferi; Neuroborreliosis; Post-lyme disease syndrome; Cerebrospinal fluid; Antibiotic
Introduction
Patients with neuroborreliosis generally present with a
typical pattern involving the time course, constellation of
signs, and cerebrospinal fluid (CSF) abnormalities. The
best indicator of active neuroborreliosis is CSF inflammation
with lymphocytic pleocytosis and a Borrelia
burgdorferi-specific intrathecal antibody response (Stanek
et al., 1996; Rauer et al., 2005). This response is
usually detected 2?3 weeks after onset of neurological
symptoms and in nearly 100% of the patients who have
had the disease for 8 weeks or more (Hansen, 1994).
Spectrum of neurological manifestations in adult patients
Acute neuroborreliosis
The most common neurological manifestation during
stage II of Lyme borreliosis (acute neuroborreliosis) in
Europe is painful lymphocytic meningoradiculitis, also
known as Bannwarth?s syndrome (Bannwarth, 1941).
The hallmarks of Bannwarth?s syndrome are radicular
pain, peripheral paresis, especially of the facial nerve,
and inflammatory changes of the CSF with lymphomonocytic
pleocytosis, a white blood cell count between 10
and 1000 cells/ml, and an elevated protein content
(Kristoferitsch, 1989; Pfister et al., 1994). In a series of
310 patients with Bannwarth?s syndrome treated at our
Department of Neurology, the predominant symptom
was radicular pain (90% of the patients), 27% of the
patients had headache, and only 13% stiff neck (Pfister
et al., unpublished data). Cranial nerve palsies, especially
facial nerve palsies, were found in 35% of the
patients.MRI may reveal contrast enhancement of basal
meninges.
In contrast to its frequency in adults, Bannwarth?s
syndrome is rather rare in children, occurring in less
than 5% of the patients with neuroborreliosis (Christen,
1996). The most common manifestations in children
with neuroborreliosis are acute facial nerve palsy (55%
of the patients) and lymphocytic meningitis (27%)
(Christen, 1996).
Apart from Bannwarth?s syndrome and lymphocytic
meningitis, other neurological manifestions of Lyme
borreliosis during stage II are cranial neuritis, plexus
neuritis, mononeuritis multiplex, and, rarely, acute
encephalitis and myelitis (Pachner and Steere, 1985;
Pfister et al., 1986, 1994; Stanek and Strle, 2003).
Chronic neuroborreliosis
Late chronic organ involvement may occur months to
years after infection (Pfister et al., 1994; Stanek and
Strle, 2003; Steere et al., 2004). Late neurological
manifestations (chronic neuroborreliosis), which are
very rare, include the following:
chronic progressive Lyme encephalitides or encephalomyelitides,
most frequently presenting with tetraspastic
syndrome, spastic-ataxic gait disorder, and
disturbed micturition (Ackermann et al., 1985;
Kohlhepp et al., 1986);
cerebral vasculitis (the predilection site is the vertebrobasilar
system with risk of infarctions of the
brainstem, thalamus, and cerebellum) (May and
Jabbari, 1990);
myositis (with paresis and focal pain) (Schmutzhard
et al., 1986; Reimers et al., 1993); and
chronic polyneuropathy, mainly of the axonal type
(Hopf, 1975; Kristoferitsch, 1989; Halperin et al.,
1990). In European patients, the polyneuropathy due
to Borrelia infection is associated with acrodermatitis
chronica atrophicans, the typical dermatological
manifestation during stage III of B. burgdorferi
infection (Hopf, 1975). Isolated cases of polyneuropathy
that evolves independently of acrodermatitis
chronica atrophicans and without other typical
symptoms of Borrelia infection have been reported
in American patients (Halperin et al., 1990; Logigian
et al., 1990), but rarely, if ever, in European patients.
A causal relationship has not been proven for
polyneuropathy and positive Borrelia antibodies in
serum, since positive Borrelia antibodies can be
detected in the serum of 5?25% of healthy persons
(Kaiser et al., 1997). Their frequency is dependent on
the age group and endemic area investigated. Thus,
the diagnostic likelihood of a Borrelia-induced
chronic polyneuropathy depends on the presence of
other typical Lyme borreliosis manifestations, the
differential diagnostic exclusion of other causes of
polyneuropathy, and the presence of inflammatory
CSF changes.
Differential diagnoses
Differential diagnoses of neuroborreliosis with the
predominant syndrome of lymphocytic meningitis include
viral meningitis, carcinomatous meningitis, neurosarcoidosis,
fungal meningitis, tuberculous meningitis,
Mollaret?s meningitis, and other spirochetal infections
such as syphilis, leptospirosis, and relapsing fever.
Peripheral facial palsy requires diagnostic differentiation
from Guillain?Barre´ syndrome, Miller?Fisher
syndrome, and idiopathic facial palsy. The intense
radicular pain of Bannwarth?s syndrome often initially
suggests a herniated disk or herpes zoster radiculitis.
The predominant neurological signs of chronic progressive
Lyme encephalomyelitis frequently include spastic
paresis or cerebellar ataxia. Cranial magnetic resonance
tomography may reveal areas of increased signal
intensity on T2-weighted scans in periventricular distribution.
Therefore, differential diagnostic problems to
distinguish it from multiple sclerosis may arise. However,
both diseases can be differentiated from each
other. Chronic neuroborreliosis is mainly characterized
by a progressive course. The relapsing, remitting course
typical of multiple sclerosis seems to be very rare in
chronic neuroborreliosis. In contrast to multiple sclerosis,
the CSF of patients with chronic neuroborreliosis
frequently reveals markedly elevated lymphomonocytic
cell counts (435 cells/ml) and total protein content
(4100 mg/dl). The crucial factor for differentiating
chronic neuroborreliosis and multiple sclerosis is the
detection of specific intrathecal antibody production
against B. burgdorferi.
Diagnostic procedures
B. burgdorferi can be isolated in special laboratories
from the CSF of approximately 10?15% of patients with
Bannwarth?s syndrome (Wilske and Preac-Mursic,
1993). Detection of Borrelia DNA from CSF by PCR
gives approximately the same diagnostic yield (Hansen,
1994; Christen et al., 1995). Successful isolation of
Borrelia from the CSF of chronic neuroborreliosis
patients has not yet been reported.
At present, serological methods are primarily used
for the microbiological diagnosis of Lyme borreliosis.
A two-test approach using a sensitive enzyme immunoassay
(EIA) followed by a Western immunoblot is the
algorithm of choice (Wilske et al., 2000). All specimens
that are positive or equivocal on a sensitive EIA should
be retested with a standardized Western immunoblot.
Specimens that are negative on a sensitive EIA need not
be tested further. The sensitivity and specificity of
Borrelia antibody detection have been improved by the
development of immunodominant, recombinant antigens.
Here the recently discovered Borrelia antigens
VlsE and DbpA are of special relevance (Schulte-
Spechtel et al., 2003).
A CSF analysis in patients with neuroborreliosis
reveals lymphocytic pleocytosis. To detect intrathecal
Borrelia-specific antibody production, the CSF-to-serum
Borrelia antibody index (AI) has to be calculated
(Hansen and Lebech, 1992; Kaiser and Rauer, 1998).
This Borrelia AI is the ratio of specific CSF-to-serum
antibodies and the CSF-to-serum ratio of albumin or
IgG. It allows discrimination between elevated CSF
B. burgdorferi antibodies caused by a passive transfer
due to a blood?CSF-barrier dysfunction and those
caused by intrathecal production. Depending on the
clinical and laboratory findings, the diagnosis of
neuroborreliosis is classified as possible, probable, or
definite (Table 1; Rauer et al., 2005).
The presence of only elevated serum IgG antibodies
indicates previous exposure to B. burgdorferi; it does not
prove active infection. The prevalence of IgG antibodies
to B. burgdorferi in populations of endemic areas and in
persons at high risk of acquiring a tick bite, e.g. forestry
workers, most of whom are clinically asymptomatic,
poses an important problem in the serodiagnosis of
Lyme borreliosis.
The following laboratory methods are not suitable for
the diagnosis of neuroborreliosis: antigen detection from
body fluids, PCR of serum or urine, the lymphocytic
transformation test (LTT), and the so-called ?visual
contrast sensitivity test? (Wilske, 2003; Anonymous,
2005).
Therapy of neuroborreliosis
Patients with active neuroborreliosis should receive a
2-week (stage II neuroborreliosis) or 3-week (stage III
neuroborreliosis) course of antibiotic therapy (usually
ceftriaxone 2 g/day i.v.) (Table 2; Rauer et al., 2005).
Several studies have shown that doxycycline is effective
in acute neuroborreliosis (Dotevall et al., 1988; Karkkonen
et al., 2001). There are no controlled studies
comparing different dosages of doxycycline in patients
with neuroborreliosis. The standard dosage of doxycycline
is 200 mg/day; however, 300 mg daily dosage might
be required to achieve adequate CSF concentrations
(Dotevall and Hagberg, 1989). Treatment failures are
extremely rare. Suspected relapses should lead to a
repeated CSF examination for the persistence of CSF
pleocytosis.
A routine follow-up lumbar puncture is recommended
6 months after antibiotic therapy. As in neurosyphilis,
successful antibiotic therapy should lead to the normalization
of CSF pleocytosis within half a year. If CSF
pleocytosis is persistent, another antibiotic course is
recommended. Oligoclonal IgG bands and specific
antibodies against B. burgdorferi may persist in the
CSF for years or even decades and are not considered a
parameter for active disease (Hansen and Lebech, 1992;
Hammers-Berggren et al., 1993). In addition, the course
of the serum IgG antibodies to B. burgdorferi after
antibiotic therapy is heterogeneous and is not a useful
tool to judge treatment response. Persistently elevated
serum IgG and IgM antibody titres do not automatically
indicate ongoing infection (Hammers-Berggren
et al., 1993; Kalish et al., 2001). Thus, antibiotic
response is based on the presence or absence of
neurological symptoms and signs, as well as inflammatory
CSF findings.
Table 1. Diagnostic criteria of human neuroborreliosisa
Possible neuroborreliosis Typical clinical features (e.g. meningitis, meningoradiculitis, cranial nerve deficits)
Borrelia specific IgG and/or IgM serum antibodies
CSF findings not available/lumbar puncture not performed
Probable neuroborreliosis Criteria of possible neuroborreliosis plus
inflammatory CSF changes (pleocytosis, elevated protein content, intrathecal IgG
antibody production)
exclusion of other causes
Definite (proven) neuroborreliosis Criteria of probable neuroborreliosis plus
intrathecal Borrelia antibody production (and/or positive culture or PCR)
Table 2. Therapy of human neuroborreliosis in adultsa
Acute neuroborreliosis
Ceftriaxoneb 12 g/day i.v. for 2 weeks
Alternative
Doxycycline 2(?3)100 mg/day orallyc for 2 weeks
Chronic neuroborreliosis
Ceftriaxoneb 12 g/day i.v. for (2?)3 weeksd
Alternative
Doxycycline 2(3)100 mg/day orallyc for (2?)3 weeksd
aAccording to the recommendations of an expert group of the
German Neurological Society (Rauer et al., 2005).
bOr cefotaxime 32 g/day.
cOptimal daily dosage currently not known.
dOptimal treatment duration currently not known.
Post-Lyme disease (PLD) syndrome
A number of patients have persistent chronic complaints
that last more than 6 months after previous
treatment of Lyme borreliosis (Stanek and Strle, 2003).
These include musculoskeletal or radicular pain, dysaesthesia,
and neurocognitive symptoms that are often
associated with fatigue. This condition of unspecific
persistent symptoms in association with a positive
serology is termed ?PLD syndrome? (Steiner, 2003).
The PLD syndrome is reported to be much less
common in Europe than in America. Clear diagnostic
criteria for this condition are lacking (Steiner, 2003). Its
pathogenesis is not known. A persistent (ongoing)
infection or post-infectious immune-mediated mechanisms
have been implicated. Others have questioned if
the PLD syndrome is really an organic condition or
primarily a psychiatric disorder.
Recent controlled trials investigating whether prolonged
antibiotic treatment is effective for patients with
the PLD syndrome showed that additional antibiotic
therapy was not more beneficial than a placebo
(Klempner et al., 2001; Kaplan et al., 2003). However,
due to the absence of accepted diagnostic criteria or
biological markers, the interpretation of these data is
limited by the heterogeneity of the patient groups studied.
Recently, a community-based longitudinal cohort
study showed that the frequencies of reports of both
increased symptoms (e.g. headaches, memory problems,
neck pain, or fatigue) and increased difficulties with
typical activities (e.g. attending school or work, doing
housework, or sleeping) among patients who had been
diagnosed as having Lyme disease were similar to those
among age-matched controls without Lyme disease
(Seltzer et al., 2000). In clinical practice, the presence
of unspecific symptoms and complaints such as fatigue,
difficulty in sleeping, cognitive impairment, headache,
arthralgia, and myalgia is in principle no indication for
Borrelia serological tests, since the predictive value of a
positive finding is very low (Rauer et al., 2005).
Unspecific symptoms should prompt a search for
relevant differential diagnoses, e.g., hypothyroidism,
autoimmune disease, or polymyalgia rheumatica. If
Borrelia serological tests had been performed and they
were positive, then the positive serological findings have to
be confirmed in a reference laboratory. If confirmed and
other causes for the symptoms have been excluded, one
course of antibiotic therapy (e.g. oral doxycycline for 3
weeks) may be considered in single cases. However, when
choosing this strategy, it should be kept in mind that:
(1) there is no evidence for the effect of such a strategy
(see above) and
(2) serious side effects of antibiotics are possible (e.g.
allergic reactions and diarrhoea) (Reid et al., 1998;
Patel et al., 2000).
If there is a transient ?antibiotic treatment effect?, a
placebo effect or positive antiphlogistic side effects of
antibiotics (e.g. antioxidative effects) have to be
considered. The absence of a persistent effect of
antibiotics argues against Borrelia infection, and further
antibiotic courses are not indicated and should be
avoided. Symptomatic treatment strategies (e.g. amitriptyline
for pain syndromes) must be initiated.
Conclusions
The diagnosis of active neuroborreliosis is based on
the presence of lymphomonocytic pleocytosis in the CSF
and intrathecal borrelia antibody production. Therapy
consists of a 2?3-week course of intravenous antibiotic
(ceftriaxone) therapy. Patients with PLD syndrome and
unspecific symptoms and complaints such as fatigue,
difficulty sleeping, cognitive impairment, headache,
arthralgia, and myalgia should receive symptomatic
therapies, since controlled studies have shown that
antibiotic therapy (for 1?3 months) was no more
beneficial than placebo.
Edellinen tutkimus pidempänä versiona:
International Journal of Medical Microbiology
MINI-REVIEW
Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients
Hans-Walter Pfister, Tobias A. Rupprecht
Department of Neurology, Ludwig-Maximilians-University, Klinikum Großhadern, Marchioninistrasse 15,
D-81377 Munich, Germany
Abstract
The diagnostic criteria of active neuroborreliosis include inflammatory changes of the cerebrospinal fluid (CSF) and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production. Patients with neuroborreliosis are usually treated with intravenous ceftriaxone for 2?3 weeks. In case of allergy, doxycycline may be used. Treatment efficacy is detected by the improvement of the neurological symptoms and the normalization of the CSF pleocytosis. The measurement of serum and CSF antibodies is not suitable for follow-up, because they frequently persist. Post-Lyme disease (PLD) syndrome is characterized by persistent complaints and symptoms after previous treatment for Lyme borreliosis, e.g., musculoskeletal or radicular pain, dysaesthesia, and neurocognitive symptoms that are often associated with fatigue. There is no formal definition of the PLD syndrome, and its pathogenesis is unclear. Recent controlled studies do not support the use of additional antibiotics in these patients, but recommend primarily symptomatic strategies.
r 2006 Elsevier GmbH. All rights reserved.
Keywords: Borrelia burgdorferi; Neuroborreliosis; Post-lyme disease syndrome; Cerebrospinal fluid; Antibiotic
Introduction
Patients with neuroborreliosis generally present with a
typical pattern involving the time course, constellation of
signs, and cerebrospinal fluid (CSF) abnormalities. The
best indicator of active neuroborreliosis is CSF inflammation
with lymphocytic pleocytosis and a Borrelia
burgdorferi-specific intrathecal antibody response (Stanek
et al., 1996; Rauer et al., 2005). This response is
usually detected 2?3 weeks after onset of neurological
symptoms and in nearly 100% of the patients who have
had the disease for 8 weeks or more (Hansen, 1994).
Spectrum of neurological manifestations in adult patients
Acute neuroborreliosis
The most common neurological manifestation during
stage II of Lyme borreliosis (acute neuroborreliosis) in
Europe is painful lymphocytic meningoradiculitis, also
known as Bannwarth?s syndrome (Bannwarth, 1941).
The hallmarks of Bannwarth?s syndrome are radicular
pain, peripheral paresis, especially of the facial nerve,
and inflammatory changes of the CSF with lymphomonocytic
pleocytosis, a white blood cell count between 10
and 1000 cells/ml, and an elevated protein content
(Kristoferitsch, 1989; Pfister et al., 1994). In a series of
310 patients with Bannwarth?s syndrome treated at our
Department of Neurology, the predominant symptom
was radicular pain (90% of the patients), 27% of the
patients had headache, and only 13% stiff neck (Pfister
et al., unpublished data). Cranial nerve palsies, especially
facial nerve palsies, were found in 35% of the
patients.MRI may reveal contrast enhancement of basal
meninges.
In contrast to its frequency in adults, Bannwarth?s
syndrome is rather rare in children, occurring in less
than 5% of the patients with neuroborreliosis (Christen,
1996). The most common manifestations in children
with neuroborreliosis are acute facial nerve palsy (55%
of the patients) and lymphocytic meningitis (27%)
(Christen, 1996).
Apart from Bannwarth?s syndrome and lymphocytic
meningitis, other neurological manifestions of Lyme
borreliosis during stage II are cranial neuritis, plexus
neuritis, mononeuritis multiplex, and, rarely, acute
encephalitis and myelitis (Pachner and Steere, 1985;
Pfister et al., 1986, 1994; Stanek and Strle, 2003).
Chronic neuroborreliosis
Late chronic organ involvement may occur months to
years after infection (Pfister et al., 1994; Stanek and
Strle, 2003; Steere et al., 2004). Late neurological
manifestations (chronic neuroborreliosis), which are
very rare, include the following:
chronic progressive Lyme encephalitides or encephalomyelitides,
most frequently presenting with tetraspastic
syndrome, spastic-ataxic gait disorder, and
disturbed micturition (Ackermann et al., 1985;
Kohlhepp et al., 1986);
cerebral vasculitis (the predilection site is the vertebrobasilar
system with risk of infarctions of the
brainstem, thalamus, and cerebellum) (May and
Jabbari, 1990);
myositis (with paresis and focal pain) (Schmutzhard
et al., 1986; Reimers et al., 1993); and
chronic polyneuropathy, mainly of the axonal type
(Hopf, 1975; Kristoferitsch, 1989; Halperin et al.,
1990). In European patients, the polyneuropathy due
to Borrelia infection is associated with acrodermatitis
chronica atrophicans, the typical dermatological
manifestation during stage III of B. burgdorferi
infection (Hopf, 1975). Isolated cases of polyneuropathy
that evolves independently of acrodermatitis
chronica atrophicans and without other typical
symptoms of Borrelia infection have been reported
in American patients (Halperin et al., 1990; Logigian
et al., 1990), but rarely, if ever, in European patients.
A causal relationship has not been proven for
polyneuropathy and positive Borrelia antibodies in
serum, since positive Borrelia antibodies can be
detected in the serum of 5?25% of healthy persons
(Kaiser et al., 1997). Their frequency is dependent on
the age group and endemic area investigated. Thus,
the diagnostic likelihood of a Borrelia-induced
chronic polyneuropathy depends on the presence of
other typical Lyme borreliosis manifestations, the
differential diagnostic exclusion of other causes of
polyneuropathy, and the presence of inflammatory
CSF changes.
Differential diagnoses
Differential diagnoses of neuroborreliosis with the
predominant syndrome of lymphocytic meningitis include
viral meningitis, carcinomatous meningitis, neurosarcoidosis,
fungal meningitis, tuberculous meningitis,
Mollaret?s meningitis, and other spirochetal infections
such as syphilis, leptospirosis, and relapsing fever.
Peripheral facial palsy requires diagnostic differentiation
from Guillain?Barre´ syndrome, Miller?Fisher
syndrome, and idiopathic facial palsy. The intense
radicular pain of Bannwarth?s syndrome often initially
suggests a herniated disk or herpes zoster radiculitis.
The predominant neurological signs of chronic progressive
Lyme encephalomyelitis frequently include spastic
paresis or cerebellar ataxia. Cranial magnetic resonance
tomography may reveal areas of increased signal
intensity on T2-weighted scans in periventricular distribution.
Therefore, differential diagnostic problems to
distinguish it from multiple sclerosis may arise. However,
both diseases can be differentiated from each
other. Chronic neuroborreliosis is mainly characterized
by a progressive course. The relapsing, remitting course
typical of multiple sclerosis seems to be very rare in
chronic neuroborreliosis. In contrast to multiple sclerosis,
the CSF of patients with chronic neuroborreliosis
frequently reveals markedly elevated lymphomonocytic
cell counts (435 cells/ml) and total protein content
(4100 mg/dl). The crucial factor for differentiating
chronic neuroborreliosis and multiple sclerosis is the
detection of specific intrathecal antibody production
against B. burgdorferi.
Diagnostic procedures
B. burgdorferi can be isolated in special laboratories
from the CSF of approximately 10?15% of patients with
Bannwarth?s syndrome (Wilske and Preac-Mursic,
1993). Detection of Borrelia DNA from CSF by PCR
gives approximately the same diagnostic yield (Hansen,
1994; Christen et al., 1995). Successful isolation of
Borrelia from the CSF of chronic neuroborreliosis
patients has not yet been reported.
At present, serological methods are primarily used
for the microbiological diagnosis of Lyme borreliosis.
A two-test approach using a sensitive enzyme immunoassay
(EIA) followed by a Western immunoblot is the
algorithm of choice (Wilske et al., 2000). All specimens
that are positive or equivocal on a sensitive EIA should
be retested with a standardized Western immunoblot.
Specimens that are negative on a sensitive EIA need not
be tested further. The sensitivity and specificity of
Borrelia antibody detection have been improved by the
development of immunodominant, recombinant antigens.
Here the recently discovered Borrelia antigens
VlsE and DbpA are of special relevance (Schulte-
Spechtel et al., 2003).
A CSF analysis in patients with neuroborreliosis
reveals lymphocytic pleocytosis. To detect intrathecal
Borrelia-specific antibody production, the CSF-to-serum
Borrelia antibody index (AI) has to be calculated
(Hansen and Lebech, 1992; Kaiser and Rauer, 1998).
This Borrelia AI is the ratio of specific CSF-to-serum
antibodies and the CSF-to-serum ratio of albumin or
IgG. It allows discrimination between elevated CSF
B. burgdorferi antibodies caused by a passive transfer
due to a blood?CSF-barrier dysfunction and those
caused by intrathecal production. Depending on the
clinical and laboratory findings, the diagnosis of
neuroborreliosis is classified as possible, probable, or
definite (Table 1; Rauer et al., 2005).
The presence of only elevated serum IgG antibodies
indicates previous exposure to B. burgdorferi; it does not
prove active infection. The prevalence of IgG antibodies
to B. burgdorferi in populations of endemic areas and in
persons at high risk of acquiring a tick bite, e.g. forestry
workers, most of whom are clinically asymptomatic,
poses an important problem in the serodiagnosis of
Lyme borreliosis.
The following laboratory methods are not suitable for
the diagnosis of neuroborreliosis: antigen detection from
body fluids, PCR of serum or urine, the lymphocytic
transformation test (LTT), and the so-called ?visual
contrast sensitivity test? (Wilske, 2003; Anonymous,
2005).
Therapy of neuroborreliosis
Patients with active neuroborreliosis should receive a
2-week (stage II neuroborreliosis) or 3-week (stage III
neuroborreliosis) course of antibiotic therapy (usually
ceftriaxone 2 g/day i.v.) (Table 2; Rauer et al., 2005).
Several studies have shown that doxycycline is effective
in acute neuroborreliosis (Dotevall et al., 1988; Karkkonen
et al., 2001). There are no controlled studies
comparing different dosages of doxycycline in patients
with neuroborreliosis. The standard dosage of doxycycline
is 200 mg/day; however, 300 mg daily dosage might
be required to achieve adequate CSF concentrations
(Dotevall and Hagberg, 1989). Treatment failures are
extremely rare. Suspected relapses should lead to a
repeated CSF examination for the persistence of CSF
pleocytosis.
A routine follow-up lumbar puncture is recommended
6 months after antibiotic therapy. As in neurosyphilis,
successful antibiotic therapy should lead to the normalization
of CSF pleocytosis within half a year. If CSF
pleocytosis is persistent, another antibiotic course is
recommended. Oligoclonal IgG bands and specific
antibodies against B. burgdorferi may persist in the
CSF for years or even decades and are not considered a
parameter for active disease (Hansen and Lebech, 1992;
Hammers-Berggren et al., 1993). In addition, the course
of the serum IgG antibodies to B. burgdorferi after
antibiotic therapy is heterogeneous and is not a useful
tool to judge treatment response. Persistently elevated
serum IgG and IgM antibody titres do not automatically
indicate ongoing infection (Hammers-Berggren
et al., 1993; Kalish et al., 2001). Thus, antibiotic
response is based on the presence or absence of
neurological symptoms and signs, as well as inflammatory
CSF findings.
Table 1. Diagnostic criteria of human neuroborreliosisa
Possible neuroborreliosis Typical clinical features (e.g. meningitis, meningoradiculitis, cranial nerve deficits)
Borrelia specific IgG and/or IgM serum antibodies
CSF findings not available/lumbar puncture not performed
Probable neuroborreliosis Criteria of possible neuroborreliosis plus
inflammatory CSF changes (pleocytosis, elevated protein content, intrathecal IgG
antibody production)
exclusion of other causes
Definite (proven) neuroborreliosis Criteria of probable neuroborreliosis plus
intrathecal Borrelia antibody production (and/or positive culture or PCR)
Table 2. Therapy of human neuroborreliosis in adultsa
Acute neuroborreliosis
Ceftriaxoneb 12 g/day i.v. for 2 weeks
Alternative
Doxycycline 2(?3)100 mg/day orallyc for 2 weeks
Chronic neuroborreliosis
Ceftriaxoneb 12 g/day i.v. for (2?)3 weeksd
Alternative
Doxycycline 2(3)100 mg/day orallyc for (2?)3 weeksd
aAccording to the recommendations of an expert group of the
German Neurological Society (Rauer et al., 2005).
bOr cefotaxime 32 g/day.
cOptimal daily dosage currently not known.
dOptimal treatment duration currently not known.
Post-Lyme disease (PLD) syndrome
A number of patients have persistent chronic complaints
that last more than 6 months after previous
treatment of Lyme borreliosis (Stanek and Strle, 2003).
These include musculoskeletal or radicular pain, dysaesthesia,
and neurocognitive symptoms that are often
associated with fatigue. This condition of unspecific
persistent symptoms in association with a positive
serology is termed ?PLD syndrome? (Steiner, 2003).
The PLD syndrome is reported to be much less
common in Europe than in America. Clear diagnostic
criteria for this condition are lacking (Steiner, 2003). Its
pathogenesis is not known. A persistent (ongoing)
infection or post-infectious immune-mediated mechanisms
have been implicated. Others have questioned if
the PLD syndrome is really an organic condition or
primarily a psychiatric disorder.
Recent controlled trials investigating whether prolonged
antibiotic treatment is effective for patients with
the PLD syndrome showed that additional antibiotic
therapy was not more beneficial than a placebo
(Klempner et al., 2001; Kaplan et al., 2003). However,
due to the absence of accepted diagnostic criteria or
biological markers, the interpretation of these data is
limited by the heterogeneity of the patient groups studied.
Recently, a community-based longitudinal cohort
study showed that the frequencies of reports of both
increased symptoms (e.g. headaches, memory problems,
neck pain, or fatigue) and increased difficulties with
typical activities (e.g. attending school or work, doing
housework, or sleeping) among patients who had been
diagnosed as having Lyme disease were similar to those
among age-matched controls without Lyme disease
(Seltzer et al., 2000). In clinical practice, the presence
of unspecific symptoms and complaints such as fatigue,
difficulty in sleeping, cognitive impairment, headache,
arthralgia, and myalgia is in principle no indication for
Borrelia serological tests, since the predictive value of a
positive finding is very low (Rauer et al., 2005).
Unspecific symptoms should prompt a search for
relevant differential diagnoses, e.g., hypothyroidism,
autoimmune disease, or polymyalgia rheumatica. If
Borrelia serological tests had been performed and they
were positive, then the positive serological findings have to
be confirmed in a reference laboratory. If confirmed and
other causes for the symptoms have been excluded, one
course of antibiotic therapy (e.g. oral doxycycline for 3
weeks) may be considered in single cases. However, when
choosing this strategy, it should be kept in mind that:
(1) there is no evidence for the effect of such a strategy
(see above) and
(2) serious side effects of antibiotics are possible (e.g.
allergic reactions and diarrhoea) (Reid et al., 1998;
Patel et al., 2000).
If there is a transient ?antibiotic treatment effect?, a
placebo effect or positive antiphlogistic side effects of
antibiotics (e.g. antioxidative effects) have to be
considered. The absence of a persistent effect of
antibiotics argues against Borrelia infection, and further
antibiotic courses are not indicated and should be
avoided. Symptomatic treatment strategies (e.g. amitriptyline
for pain syndromes) must be initiated.
Conclusions
The diagnosis of active neuroborreliosis is based on
the presence of lymphomonocytic pleocytosis in the CSF
and intrathecal borrelia antibody production. Therapy
consists of a 2?3-week course of intravenous antibiotic
(ceftriaxone) therapy. Patients with PLD syndrome and
unspecific symptoms and complaints such as fatigue,
difficulty sleeping, cognitive impairment, headache,
arthralgia, and myalgia should receive symptomatic
therapies, since controlled studies have shown that
antibiotic therapy (for 1?3 months) was no more
beneficial than placebo.
Viimeksi muokannut Bb, La Maalis 07, 2009 12:53. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 20.3.2006 9:11
Immuunijärjestelmän toiminta näyttää olevan keskeisessä asemassa borrelioosissa (todennäköisesti lähes kaikissa sairauksissa). Se kehittyykö borrelioosi krooniseksi vai ei näyttää seuraavien tutkimusten mukaan riippuvan siitä miten immuunijärjestelmä reagoi borreliabakteeriin taudin alkuvaiheessa.
Kroonista neuroborrelioosia sairastavilla ilmeni alhaisia TNF- ja TGF beta- pitoisuuksia veressä ja selkäydinnesteessä. Neuroborrelioosia sairastavilta löydettiin toisessa tutkimuksessa kohonneita interferoni gamma -pitoisuuksia verestä ja selkäydinnesteestä. Pitoisuus pysyi korkeana koko seuranta-ajan (9 kk) vaikka henkilöt olivat saaneet antibioottihoidot ja olivat sillä hetkellä pääosin oireettomia. (Ruotsi)
Scand J Immunol. 1995 Dec;42(6):694-700.
Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.
Wang WZ, Fredrikson S, Sun JB, Link H.
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi- reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.
PMID: 8552994 [PubMed - indexed for MEDLINE]
-------------
Immunology. 2002 Sep;107(1):46-55. Related Articles, Links
Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-alpha and transforming growth factor-beta1 responses are associated with chronic neuroborreliosis.
Widhe M, Grusell M, Ekerfelt C, Vrethem M, Forsberg P, Ernerudh J.
Division of Clinical Immunology, Faculty of Health Sciences, University of Linkoping, Sweden. mona.widhe@imk.liu.se
The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7).
When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-alpha were found in non-chronic patients than in chronic patients (P<0.05). Moreover, TGF-beta1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0.01). Elevated serum levels of TGF-beta1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0.05). The high TNF-alpha levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-beta1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.
PMID: 12225362 [PubMed - indexed for MEDLINE]
Immuunijärjestelmän toiminta näyttää olevan keskeisessä asemassa borrelioosissa (todennäköisesti lähes kaikissa sairauksissa). Se kehittyykö borrelioosi krooniseksi vai ei näyttää seuraavien tutkimusten mukaan riippuvan siitä miten immuunijärjestelmä reagoi borreliabakteeriin taudin alkuvaiheessa.
Kroonista neuroborrelioosia sairastavilla ilmeni alhaisia TNF- ja TGF beta- pitoisuuksia veressä ja selkäydinnesteessä. Neuroborrelioosia sairastavilta löydettiin toisessa tutkimuksessa kohonneita interferoni gamma -pitoisuuksia verestä ja selkäydinnesteestä. Pitoisuus pysyi korkeana koko seuranta-ajan (9 kk) vaikka henkilöt olivat saaneet antibioottihoidot ja olivat sillä hetkellä pääosin oireettomia. (Ruotsi)
Scand J Immunol. 1995 Dec;42(6):694-700.
Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.
Wang WZ, Fredrikson S, Sun JB, Link H.
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi- reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.
PMID: 8552994 [PubMed - indexed for MEDLINE]
-------------
Immunology. 2002 Sep;107(1):46-55. Related Articles, Links
Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-alpha and transforming growth factor-beta1 responses are associated with chronic neuroborreliosis.
Widhe M, Grusell M, Ekerfelt C, Vrethem M, Forsberg P, Ernerudh J.
Division of Clinical Immunology, Faculty of Health Sciences, University of Linkoping, Sweden. mona.widhe@imk.liu.se
The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7).
When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-alpha were found in non-chronic patients than in chronic patients (P<0.05). Moreover, TGF-beta1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0.01). Elevated serum levels of TGF-beta1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0.05). The high TNF-alpha levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-beta1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.
PMID: 12225362 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, La Maalis 07, 2009 12:56. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 22.3.2006 8:26
Uuden tutkimuksen mukaan näyttää siltä että elimistön tietyt lipoproteiinit (Erp) suojelevat borreliabakteeria ja mahdollistavat näin sen selviytymisen kudoksissa immuunijärjestelmän tuhoamisyrityksiltä:
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Int J Med Microbiol. 2006 Mar 8; [Epub ahead of print]
Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts.
Miller JC, Stevenson B.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MS 415 Chandler Medical Center, Lexington, KY 40536-0298, USA.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans and other vertebrate hosts through the bites of ixodid ticks. B. burgdorferi Erp (OspE-F related lipoprotein) family members are encoded on members of the 32kb circular plasmid-like prophage family (cp32s). Many Erp proteins serve as receptors for the complement inhibitory factor H molecules of numerous vertebrate hosts, providing one mechanism by which the bacteria potentially evade the innate immune system. Indirect immunofluorescence analyses (IFA) have demonstrated that Erp expression is temporally regulated throughout the mammal-tick infectious cycle, indicating that Erp proteins perform an important role (or even roles) during mammalian infection. However, it was not previously known whether Erp proteins are continually produced by B. burgdorferi throughout the course of mammalian infection. To address this issue, quantitative RT-PCR (q-RT-PCR) was utilized to assess erp transcription levels by bacteria within numerous different tissues of both mice and non-human primates (NHPs) chronically infected with B. burgdorferi. Q-RT-PCR results obtained using both animal models indicated that while the majority of erp genes were detectably transcribed during chronic infection, differences in expression levels were noted. These data strongly suggest that Erp proteins contribute to B. burgdorferi persistence within chronically infected host tissues, perhaps by protecting the bacteria from complement-mediated killing.
PMID: 16530008 [PubMed - as supplied by publisher]
Uuden tutkimuksen mukaan näyttää siltä että elimistön tietyt lipoproteiinit (Erp) suojelevat borreliabakteeria ja mahdollistavat näin sen selviytymisen kudoksissa immuunijärjestelmän tuhoamisyrityksiltä:
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Int J Med Microbiol. 2006 Mar 8; [Epub ahead of print]
Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts.
Miller JC, Stevenson B.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MS 415 Chandler Medical Center, Lexington, KY 40536-0298, USA.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans and other vertebrate hosts through the bites of ixodid ticks. B. burgdorferi Erp (OspE-F related lipoprotein) family members are encoded on members of the 32kb circular plasmid-like prophage family (cp32s). Many Erp proteins serve as receptors for the complement inhibitory factor H molecules of numerous vertebrate hosts, providing one mechanism by which the bacteria potentially evade the innate immune system. Indirect immunofluorescence analyses (IFA) have demonstrated that Erp expression is temporally regulated throughout the mammal-tick infectious cycle, indicating that Erp proteins perform an important role (or even roles) during mammalian infection. However, it was not previously known whether Erp proteins are continually produced by B. burgdorferi throughout the course of mammalian infection. To address this issue, quantitative RT-PCR (q-RT-PCR) was utilized to assess erp transcription levels by bacteria within numerous different tissues of both mice and non-human primates (NHPs) chronically infected with B. burgdorferi. Q-RT-PCR results obtained using both animal models indicated that while the majority of erp genes were detectably transcribed during chronic infection, differences in expression levels were noted. These data strongly suggest that Erp proteins contribute to B. burgdorferi persistence within chronically infected host tissues, perhaps by protecting the bacteria from complement-mediated killing.
PMID: 16530008 [PubMed - as supplied by publisher]