Borrelia burgdorferi sensu lato and their implications for diagnostics, clinical appearance and treatment of Lyme-Disease The slow growing of Bb means for the infected human being: • He / she can become ill a long time after infection (latency) 1 Bb needs ca. 12-20 (8-35) hours for one generation- • treatment has to take a long time to reach as many generations as in treatment of fast-growing-bacteria ( 60 -100 x?) cf E. coli needs ca. 20 min for one generation- • Consider using therapy-principles of other slow-growing- bacteria; e.g. : M. leprae, M. tuberculosis, T. pallidum Bb sometimes needs 10 weeks for culturing • treatment of TBC: combi for at least 6 months; • similar to leprosy: ca. 2 years combi-therapy 1. Preac-Mursic et al, Infection 1996 Jan-Feb, 24 (1) 9-16; Kill kinetics of Bb and bacterial findings in relation to the treatment of LB (E. Freeksen, Borstel, Malta); before at least 10 years 2. Hassler,
1. Holger Blenk, Vorsitzender des Bundesverbandes der Ärzte für Mikrobiologie und Infektionsepidemiologe; Saarland online – 16 years latencywysi-wyg://19/http// : Borrelia burgdorferi sequester in tissue 2. Hans Schadewaldt, Über die Rückkehr der Seuchen; VGS Köln 1994, S. 68; Robugen connective tissue (present in all organs) and which is "Considering an early germ-dissemination into CNS . it seems poorly infiltrated by defence cells - the im- being necessary to reach high antibiotic-levels in target-tissues like joint-synovia or CNS. even in treatment of erythema migrans or Haupl, Burmester et al.: Persistence of Bb in ligamentous tissue from a patient with chronic LB; Arthritis Rheum 1993 Nov; 36(11): U. Neubert, Borreliosen – Therapie 1998, Fortschritte der praktischen Dermatologie und Venerolgie; ".In principle the disease symptoms result from the high affinity of the Borreliae to collagen fibre. Thus connective tissue (collagen) is particularly prone to chronic inflammatory processes. The result is vessel inflammation (vasculitis processes with perivascular infiltrates of lymphocytes and plasma cells) (literature: Meier, de Koning, Duray). Capillary occlusions lead to disturbances of the tissue-supply, e.g. the vessels by which nerves are supplied (Epineurium). This again leads to (ischaemia -) pain and increased vulnerability. So probably the periarticular decalcifying process is a consequence of the poor local supply in the bone. Borreliae can probably partly evade the the immune system by sequestering in collagen 1. Exner M., Successful vaccination for LD.; where they are inaccessible to antibiotics .“ Expert Opin. Biol.Ther. (2001) 1(5): 783-793 2. Guo et al.: Mol.Microbiol (1998) 30:711-723 Borrelia burgdorferi is able to invade human e.g. blood-cells (macrophages), fibroblasts, endothelial, • Tetracycline, Doxycycline, Minocycline • Macrolides: Roxithromycin, Azithromycin, Perhaps Bb can even survive in CNS-cells? Malawista:J Immunol 1993 Feb1; 150(3) 909-15; Persistenz in Maus-Makrophagen Ma Y, A Sturrock , JJ Weis: Intracellular localization of Borrelia burgdorferi within human endothelial cells. Infection and Immunity 59, 1991 671-678 Hunfeld et al: Standardised in vitro susceptibility testing of Bb Haupl, Burmester et al.: Persistence of Bb in ligamentous tissue from a patient with chronic LB; against well-known and newly developed antimicrobial agents - pos- Arthritis Rheum 1993 Nov; 36(11): 1621-6 sible implications for new therapeutic approaches to LD; Arthritis Rheum 2001 Jan;44(1):151-62; Insights from a novel three-dimensional in vitro model of lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia Int.Med.Microbiol.291; Suppl.33, 125-137 (2002) burgdorferi and synovial explants and fibroblasts.Franz JK, Fritze O, Rittig M, Keysser G, Priem Terekhova, Antimicrobial Agents and Chemotherapy, Nov 2002, p.3637-3640, Vol.46, No.11; Erythromycin Resistance in Bb Borrelia burgdorferi can change its appearance "Cysts" are resistant to the usual antibiotics • Metronidazole can be used against cysts by “starvation" (antibiotics, CSF) Bb can change its ap-pearance: • CNS tissue is highly permeable to it • Metronidazole can cause cancer or harm an em- a “cyst" / L-form / spheroblast can later convert to living • Possible to use other treatment options against cysts: Hydroxychloroquin (anti-malaria-drug); Brorson; Infection 1997 Jul-Aug 25(4) 240-6, Transformation of cystic forms of Borrelia burgdorferi to normal, mobile spirochetes. 1. Brorson; An in vitro study of the susceptibility of mobile and cystic Kersten; Antimicrobial Agents and Chemotherapie; May 1995; p.1127-1133: forms of Bb to hydroxychloroquine; Int Microbiol 2002 Mar;5 (1) :25-31 Effects of Penicillin, Ceftriaxon and Doxycycline on Morphology of Bb 2. Brorson: Brorson O, Brorson SH, APMIS 1999 Jun; 107 (6): 566-76, An Gruntar, Cinco: APMIS 2001 May; 109(5): 383-8; Conversion of B. garinii cystic in vitro study of the susceptibility of mobile and cystic forms of Borrelia Brorson, O., & Brorson S, Infection, 1998;26(3):144-50 (R) In vitro conversion of 3. Brorson; Int.Microbiol 2001 Dec; 4(4):209-15; Susceptibility of motile Borrelia burgdorferi to cystic forms in spinal fluid, and transformation to mobile and cystic forms of Bb to rantidine bismuth citrate spirochetes by incubation in BSK-H medium.



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