Persistence in Europe and ASia

[itsybitsyone]

Intracellular persistence of Borrelia burgdorferi in human synovial cells.
Girschick HJ, Huppertz HI, Rüssmann H, Krenn V, Karch H.
Rheumatol Int. 1996;16(3):125-32
www.ncbi.nlm.nih.gov/sites/entre ... stractPlus
Children's Hospital, University of Würzburg, Germany.
To investigate if Borrelia burgdorferi can persist in resident joint cells, an infection model using cell cultures of human synovial cells was established and compared to the interaction of Borrelia burgdorferi and human macrophages. Borrelia burgdorferi were found attached to the cell surface or folded into the cell membrane of synovial cells analysed by transmission electron and confocal laser scanning microscopy. In contrast to macrophages, morphologically intact Borrelia burgdorferi were found in the cytosol of synovial cells without engulfment by cell membrane folds or phagosomes. Borrelia burgdorferi were isolated from parallel cultures. Treatment with ceftriaxone eradicated extracellular Borrelia burgdorferi, but spirochetes were reisolated after lysis of the synovial cells. Borrelia burgdorferi persisted inside synovial cells for at least 8 weeks. These data suggested that Borrelia burgdorferi might be able to persist within resident joint cells in vivo.



Kill kinetics of Borrelia burgdorferi and bacterial findings in relation to the treatment of Lyme borreliosis.
Preac Mursic V, Marget W, Busch U, Pleterski Rigler D, Hagl S. Infection 1996 Jan-Feb; 24(1): 9-16
www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
[published erratum appears in Infection 1996 Mar-Apr;24(2):169] = "On page 12, because of technical reasons it was unfortunately not mentioned that information regarding Case I was provided by Dr. D. Hassler."]
In vitro investigation. Amoxicillin, doxycycline, cefotaxime, ceftriaxone, azithromycin and penicillin G. Killing effekt investigated during a 72h exposure in MPK-medium and human serum with negative Lyme borreliosis serological tests.. Twenty clinical isolates were used ...
Exerpts:
.. the results show that the kill kinetics of the borreliae differs from antibiotic to antibiotic. The killing rate of a given antibiotic for borreliae is less dependent on the concentration of the antibiotic than on the reaction time. Furthermore, the data show that the killing effect of isolates of B. garinii differs from that in B. afzelii species. Very interesting and unexpected is the different effect of antibiotics on isolates within one species. Also the different reaction of one strain to tested antibiotics is surprising.....
In summary, the result of killing kinetics suggest that:
1. 1. The strains of B. afzelii and B. garinii spp. react differently against antibiotics used in the treatment of Lyme disease.
2. 2. The different reactions of strains to antibiotics also exists within one species.
3. 3. There exist different effects of one antibiotic against strains tested as well as different reactions of the strain to antibiotics tested.
4. 4. The killing rate of a given antibiotic is dependent on reaction time of antibiotics.
5. 5. B. garinii strains seem to be more sensitive to antibiotic tested than B. afzelii strains.
6. 6. The antibiotics take a long time to become effective.
7. 7. The different killing kinetics of B. burgdorferi sensu lato strains can be of importance in a treatment regimen.
Furthermore, the persistense of B. burgdorferi s.l. and clinical recurrences in patients despite seemingly adequate antibiotic treatment is described. The patients had clinical disease with or without diagnostic antibody titre to B. burgdorferi. Includes five case stories showing culture confirmed relapses after 12-14 days treatment courses.
Case 1: 51y man plexus neuritis. Positive serology for Borreliae IgG, WB. Cefotaxime 3x2g a day 12 days. Antibodies to Borreliae disapperead in months. Five years later a new attack with headache and pseudoradicular pain located in the region of the right arm plexus. Negative Bb and Western Blot. Half a year later progressive cardiac pain and dyspnoe on exertion. Angiography and echocardiography revealed 3rd degre mitral insufficiency. The patient had a history of 7 years of cardiomyopathy. Mitral valve replacement was carried out. Borreliae was cultured after prolonged incubation (9 weeks) from the excised mitral valve. Bb antibodies negative (ELISA, WB, IFT).
Case 2: 13y old boy with right gonarthritis. Positive IgG and IgM serology for Borrelia. Treated with ceftriaxone 2g/day for 14 days. Joint swelling diminished, but later recurred. Six months later synovectomy grew Borrelia afzelii from synovia as well as from the effusion.
Case 3: painfull knees, treated with corticosteroid. Lyme-IFGT-IgG borderline. Treated with ceftriaxone 2g/day for 14 days. Recurrent arthritis. About half a year later IgG in serum and and synovial fluid was positive. B. afzelii was isolated from the effusion.
Case 4: 35y man. One year history of headache, intensive back pain, skin eruption (lymphocytoma benignum) and arthralgia. Serum Borrelia-titer negative. Borreliae were isolated from skin biopsy (B. garinii). Cefriaxone 2g/day 14 days. The back pain diminished, other symptoms persisted. Doxycycline dose? 10 days. Persistent arthralgias. Antibody titers against Bb s.l. negative, but Borreliae was isolated from a subsequent biopsy. Oral penicillin dose? for 14 days. The antibiotic treatment resulted in reduction of arthralgias [comment: but not symptom free, not cured?]
Case 5: 28y woman. Arthralgia multiple joints. Corticosteroids and doxycycline dose? duration?. After a 2-year history of pain and an increase in inflammation in the knee and hands synovectomy was performed. Borrelia IgM and IgG was negative, but nevertheless B. afzelii was isolated from hand synovia and the patient was treated with ceftriaxone

[itsybitsyone]

Clinical Manifestations and Epidemiological aspects leading to a diagnosis of Lyme Borreliosis: Neurological and Psychiatric Manifestation in the Course of Lyme Borreliosis.
Créange A.

Med Mal Infect. 2007 Jul-Aug;37(7-8):532-9. Epub 2007 Mar 26.
[Article in French]
Service de neurologie, centre hospitalier universitaire Henri-Mondor, APHP, université Paris-XII, 94000 Créteil, France. [e-mail]
Lyme disease is associated with various systemic and neurological manifestations. The neurological and psychiatric manifestations of Lyme disease are more frequently observed during its secondary phase (stage 2) than during its late tertiary phase (stage 3). In stage 2, cerebrospinal fluid and bacterial tests are consistent with the ongoing infection. Painful meningoradiculitis, encephalomyelitis and encephalitis, and symptoms of depression are the most characteristic at this stage. The diagnosis should be based on the association of clinical, epidemiological, and biological features. Adequate treatment usually leads to recovery. In stage 3 of the disease, the link between neurological manifestations and initial infection is uncertain. Distal axonal polyneuropathy and chronic encephalopathy are the most frequently reported presentations.



Med Mal Infect. 2007 Jul-Aug;37(7-8):479-86.
Epub 2007 Mar 23.
Treatment of Lyme borreliosis secondary and tertiary stages
Hansmann Y.
[Article in French]
Service des maladies infectieuses et tropicales, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, BP 426, 67091 Strasbourg cedex, France. [e-mail]
The treatment of secondary and tertiary Lyme borreliosis is difficult because of antibiotic lack of efficacy. This fact may be explained by several factors: the specific pathophysiology, involving not only the presence of bacteria, but also immunological reactions. There is no specific method of diagnosis resulting in difficulties for good indication of treatment and to evaluate treatment efficacy. The literature review shows that ceftriaxone and doxycycline are the two most efficient antibiotics in this indication. Even if the methodology of the published studies is not always convincing, these two antibiotics proved their efficacy in articular as well as in neurological forms of the disease. In the late stage of borreliosis, antibiotics are less efficient. Various treatment modalities with different dosage or duration of treatment cannot let us conclude on a convincing regimen.




Persistence of Borrelia burgdorferi in ligamentous tissue from a
patient with chronic Lyme borreliosis.
AUTHORS: Haupl T; Hahn G; Rittig M; Krause A; Schoerner C; Schonherr U;
Kalden JR; Burmester GR
Department of Medicine III, University of Erlangen-Nuremberg, Germany.
Arthritis Rheum 1993 Nov;36(11):1621-6

OBJECTIVE. To document the persistence of **Borrelia burgdorferi**
in ligamentous tissue samples obtained from a woman with chronic Lyme
borreliosis. METHODS. Spirochetes were isolated from samples of
ligamentous tissue, and the spirochetes were characterized
antigenetically and by molecular biology techniques. The ligamentous
tissue was examined by electron microscopy. Humoral and cellular immune
responses were analyzed.
RESULTS. Choroiditis was the first recognized manifestation of Lyme
disease in this patient. Despite antibiotic therapy, there was
progression to a chronic stage, with multisystem manifestations. The
initially significant immune system activation was followed by a loss of
the specific humoral immune response and a decrease in the cellular
immune response to B burgdorferi over the course of the disease.
"Trigger finger"
developed, and a portion of the flexor retinaculum obtained at surgery
was cultured. Viable spirochetes were identified.
Ultramorphologically, the spirochetes were situated
between collagen fibers and along fibroblasts, some of which were deeply
invaginated by these organisms. The cultured bacteria were identified as
B burgdorferi by reactions with
specific immune sera and monoclonal antibodies, and by polymerase chain
reaction amplification and Southern blot hybridization techniques.
CONCLUSION. To our knowledge, this is the first report of the isolation
of B burgdorferi from ligamentous tissue. This suggests that tendon
tissues serve as a specific site of spirochete residence in human hosts.

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Recurrent and relapsing course of borreliosis of the nervous system
Omasits M, Seiser A, Brainin M
Wien Klin Wochenschr 1990 Jan 5;102(1):4-12
Neurologische Abteilung, NO Landeskrankenhaus, Klosterneuburg
Abstract:
The clinical variability of chronic infections due to Borrelia burgdorferi is greater than previously thought. Three personal cases are presented in an overview, together with cases from the literature. Chronic spastic para- and quadriparesis, transverse myelitis and recurrent hemiparesis have been noted in such cases. Frequently, there is additional involvement of the cranial nerves. Chronic polyneuritis, mononeuritis multiplex, as well as plexus neuritis can also occur. Psychiatric manifestations can at times be predominant. Their spectrum ranges from agitated depressive states with suicidal ideas to the clinical picture of dementia. Due to the high percentage of positive antibody titre reactions in the normal population, reliable evidence of a chronic infection of the nervous system is based on the examination of the cerebrospinal fluid. Lesions seen on CT and MRI are mostly uncharacteristic and bear no clear-cut relationship to the disease. Neurological signs and symptoms can be improved by antibiotic treatment.


Persistence of Borrelia garinii and Borrelia afzelii in patients with Lyme arthritis.
Hulinska D, Votypka J, Valesova M. Int J Med Microbiol Virol Parasitol Infect Dis 1999 Jul;289(3):301-18
www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
We repeatedly detected DNA of Borrelia garinii or B. afzelii and Borrelia-like structures in the blood, joint fluid or in the synovium of 10 patients with Lyme arthritis by means of the polymerase chain reaction and immunoelectron microscopy at 2-4-month intervals in the course of two years.
All samples were analyzed using primers which amplified the 16S rRNA gene sequence of Borrelia burgdorferi sensu lato and nucleotide sequences for the OspA gene. No cross hybridization occurred with DNA from human cells and with DNA from other bacteria. Capture and labelling with monoclonal antibodies of aggregated antigens, membranes and flagellae were evident in the blood of 7 patients, in 4 synovial membranes and 2 synovial fluids. Borreliae were found in blood capillaries, in collagen and in clusters surrounding inflammatory cells in the synovium of patients with recurrent infections who carried IgM and IgG antibodies to OspA and to 83 kDa core protein.
After significant improvement for several weeks after treatment, arthritis recurred in six patients. Synoviocyte hyperplasia, inflammatory infiltration and concentric adventitial fibroplasia were seen in the synovium of the patients with persisting borreliae. Only two patients were infected with B. afzelii, the others with B. garinii.