Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens:
Gespeichert in:
1. Verfasser: | |
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Format: | Buch |
Sprache: | English |
Veröffentlicht: |
Aachen
Shaker
2004
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Schriftenreihe: | Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main
2 |
Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | XII, 256 S. Ill., graph. Darst. |
ISBN: | 3832233474 |
Internformat
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245 | 1 | 0 | |a Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens |c Klaus-Peter Hunfeld |
264 | 1 | |a Aachen |b Shaker |c 2004 | |
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490 | 1 | |a Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main |v 2 | |
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Datensatz im Suchindex
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adam_text | Contents I
Page
A. Introduction 1
A.I. Emergence of tick transmitted diseases 1
A. 1.1. Borrelia, Ehrlichia, and Babesia:
Pathogens of increasing medical relevance in Europe 3
A.2. B. burgdorferi: the causative pathogen of Lyme disease (LD) 5
A.2.1 Taxonomy, genetic diversity, and microbiologic properties of
B. burgdorferi 5
A.2.2. Epidemiology ofLD in Europe 8
A.2.3. Clinical manifestations 11
A.2.4. Microbiological diagnosis 15
A.2.5. Treatment and antimicrobial susceptibility patterns 22
A.3. Granulocytic Ehrlichia spp. the causative pathogens of
Human Granulocytic Ehrlichiosis (HGE) 25
A.3.1. Taxonomy, genetic diversity, and microbiologic properties
of Ehrlichia spp. 25
A.3.2. Epidemiology 27
A.3.3. Clinical manifestations 29
A.3.4. Microbiological diagnosis 31
A.3.5. Treatment options and antimicrobial susceptibility pattern 33
A.4. B. microti and B. divergens: the causative pathogens of human babesiosis34
A.4.1. Taxonomy, genetic diversity, and microbiologic properties of the genus
Babesia 34
A.4.2. Epidemiology 36
A.4.3. Clinical disease manifestation 37
A.4.4. Microbiological diagnosis 39
A.4.5. Treatment and antimicrobial susceptibility patterns 41
A.5. Aims of the investigations summarised in this thesis 42
II Contents
Page
B. Results 43
B.I. Molecular characterisation of tick borne microrganisms 43
B.I.I B. burgdorferiisolates 43
B.1.2. E. phagocytophila isolates 46
B.1.3. B. microti and B. divergens isolates 47
B .2. Evaluation of serological assays used for seroepidemiological investi¬
gations and the laboratory diagnosis of human LD, ehrlichiosis,
and babesiosis 48
B.2.1. Evaluation of a newly developed recombinant ELISA (RE) for the
detection of anti B. burgdorferi IgG and IgM antibodies 48
B.2.1.1. Test sensitivity 49
B.2.1.2. Test specificity 49
B.2.1.3. Comparison with an established whole cell ELISA 50
B.2.1.4. Test performance 52
B.2.2. Systematic evaluation of diagnostic quality of LD serology:
Results from the German proficiency testing program 1999 2001 52
B.2.2.1. Participating laboratories 52
B.2.2.2. Applied test systems 53
B.2.2.3. Accuracy of test results 54
B.2.2.4. False positive and false negative test results and evaluation of test
kit quality 62
B.2.3. Evaluation of and seroepidemiological investigations with a diagnostic
IFA for the detection of IgG and IgM antibodies against E. phagocyto¬
phila. 64
B.2.3.1. Determination of cut off titers and evaluation of test specificity 64
Contents III
Page
B.2.3.2. Seroprevalence of antibodies against E. phagocytophila in patients
with LD 66
B.2.3.3. Seropositive individuals without symptoms of active LD 67
B.2.3.4. Statistical analysis 67
B.2.3.5. Incidence and prevalence of E. phagocytophila in young healthy German
subjects 67
B.2.4. Evaluation of and seroepidemiological investigations with a diagnostic
IFA for the detection of antibodies against B. microti and B. divergens 69
B.2.4.1 Determination of cut off titers and evaluation of test specificity 69
B.2.4.2. Seroprevalence of B. microti and B. divergens antibodies in tick exposed
individuals and healthy controls 74
B.2.4.2.1. Patients with EM 74
B.2.4.2.2. Individuals with positive borreliosis serology but lacking clinical
symptoms of active LD 74
B.2.4.2.3. Patients with a history of tick bite 74
B.2.4.2.4. Statistical analysis 76
B.3. Investigations of the biological activity of antibody containing
immune sera against B. burgdorferi: A promissing approach for the
development of a new class of diagnostic tests 77
B.3.1. Comparison of two laboratory methods for the determination of
serum resistance in B. burgdorferi isolates 77
B.3.1.1. Serum sensitivity among borrelial isolates to NHS 77
B.3.1.2. Deposition ofC6 and C9 on borrelial surfaces 80
B.3.2. Borreliacidal activity of early LD sera against complement resistant
B. ajzelii FEM1 wild type and an OspC lacking variant 81
IV Contents
Page
B.3.2.1. Borreliacidal effect of early LD sera against isolate FEM1 as determined
by growth inhibition assay and detection of deposited complement
components (GIA) 82
B.3.2.2. Immunoreactivity of borreliacidal Lyme disease sera with B. afzelii
outer membrane proteins 83
B.3.2.3. Growth characteristics of FEM1 variants differing with regard to OspC
expression 85
B.3.2.4. Characterisation of early Lyme disease sera with regard to their
borreliacidal activity against FEM1 variants 88
B.4. In vitro susceptibility testing of B. burgdorferi against well known
and newly developed antimicrobial agents 91
B.4.1 Evaluation of a new colorimetric microdilution method for the
in vitro susceptibility testing of B, burgdorferi against
antimicrobial substances 91
B.4.1.1. Test sensitivity 91
B.4.1.2. Test reproducibility and quality control 93
B.4.2. Characterisation of the in vitro susceptibility profile of B. burgdorferi
against antimicrobial substances under standardised test conditions 94
B.4.2.1. Penicillins 94
B.4.2.2. Oral and parenteral cephalosporins 97
B.4.2.3. Carbapenems, monobactams, glycopeptides, and fusidic acid 101
B.4.2.4. Tetracyclines 104
B.4.2.5. Aminoglycosides 106
B.4.2.6. Streptogramins, macrolides, azalides, and ketolides 108
B.4.2.7. Quinolones 111
B.5. Analysis of to vitro interactions between B. burgdorferi and newly
developed antimicrobial agents 116
B.5.1. Results of time kill experiments 116
Contents V
Page
B.5.1.1. Time kill studies performed on B. burgdorferi exposed to erythromycin,
telithromycin, and cethromycin 116
B.5.1.2. Time kill studies performed on B. burgdorferi exposed to ciprofloxacin
and gemifloxacin 118
B.5.2. Electron microscope analysis of B. burgdorferi exposed to increasing
concentrations of newly developed antimicrobial agents 120
B.5.2.1. Electron microscope analysis of B. burgdorferi exposed to cethromycin 120
B.5.2.2. Electron microscope analysis of B. burgdorferi exposed to ciprofloxacin
and gemifloxacin 122
B.5.3. Differential protein expression of B. burgdorferi exposed to increasing
concentrations of penicillin G and doxycycline 124
B.5.3.1. MIC determination 125
B.5.3.2. Identification of proteins with variable expression after exposure of
Borreliae to increasing concentrations of penicillin G and doxycycline 125
B.6. In vitro susceptibility testing of E. phagocytophila against well known
and newly developed antimicrobial agents 129
B.6.1. Evaluation of a new semiquantitative PCR based microdilution method for
in vitro susceptibility testing of £ phagocytophila against antimicrobial
substances 129
B.6.1.1. Precision and reproducibility of semiquantitative measurement of
ehrlichial growth by LightCycler 16S rDNA PCR 129
B.6.1.2. Test sensitivity 131
B.6.1.3. Test reproducibility and quality control 133
B.6.2. Characterisation of the in vitro susceptibility profile of E. phagocytophila
against antimicrobial substances as determined by a LightCycler PCR
based microdilution test method under standardised conditions 135
VI Contents
Page
C. Discussion
C.I. Serodiagnosis of LD: Diagnostic problems related to the current lack of
test standardisation 137
C. 1.1. External quality control of LD serology: The systematic approach of
the German proficiency testing program 137
C. 1.2. Quality of LD serology in the routine microbiological laboratory:
Lessons learned from the German proficiency testing program established
in 1999 138
C.1.3. Necessity of diagnostic standardisation: Future perspectives in promoting
better test quality 140
C.2. Recombinant test systems: A novel approach for a more accurate
serological diagnosis of LD 141
C.3. Tick borne pathogens other than B. burgdorferi (TOBB):
Continuing problems of epidemiology and microbiological diagnosis 144
C.3.1. Contributions to the seroepidemiology and medical significance of
E. phagocytophila in midwestern Germany 145
C.3.2. Contributions to seroepidemiology and medical significance of
Babesia spp. in midwestern Germany 148
C.4. Sensitivity testing of B. burgdorferi to human serum by growth
inhibitory assays: A new diagnostic approach to diagnosing active LD 151
C.4.1. Evaluation oftest procedures for the determination of serum resistance 151
C.4.2. Evaluation of a GIA and and an IFA for the determination of
complement resistance ofB. burgdorferi isolates 152
C.4.3. Evaluation of laboratory tests for a better characterisation of the
bactericidal immune response of human immune sera directed against
B. burgdorferi isolates 154
Contents VII
Page
C.5. Standardised in vitro susceptibility testing of Borrelia burgdorferi against
well known and newly developed antimicrobial agents
Possible implications for new therapeutic approaches in LD 158
C.5.1. In vitro susceptibility determination of the B. burgdorferi complex
against antimicrobial agents: Problems and drawbacks of current test
methods 159
C.5.2. Interactions between antimicobial agents and the test medium 161
C.5.3. Colorimetric microdilution in vitro susceptibility testing:
A novel approach to MIC determination of antimicrobial agents against
B. burgdorferi 162
C.5.4. Characterisation of borreliacidal activity of antimicrobial agents in vitro
using time kill experiments 163
C.5.5. Determination of MBCs: A more restrictive tool for characterising
borreliacidal activity 164
C.5.6. In vitro testing of B. burgdorferi against well known and recently
introduced antimicrobial agents applying a standardised methodology 165
C.5.7. Possible heterogeneity of different genospecies of the B. burgdorferi
complex with regard to their in vitro susceptibility pattern 168
C.5.8. Current problems of treatment in LD: Treatment failure, re infection,
missdiagnosis, and co infection 169
C.6. Changes in the protein expression pattern of borreliae exposed to
antimicrobial agents: Evidence for possible escape mechanisms on the
part of the pathogen? 171
C.7. Recently introduced antimicrobial agents: Possible implications for
alternative therapeutic approaches in LD and other tick borne diseases? 174
C.7.1. In vitro effectiveness of new fluoroquinolones against B. burgdorferi 174
C.7.2. In vitro effectiveness of new ketolides against B. burgdorferi 177
C.7.3. In vitro susceptibility testing of E. phagocytophila against well known
and recently introduced antimicrobial agents by use of a new semiquanti
tative PCR based testing method developed for fastidious organisms 181
VIII Contents
Page
C.7.4. New therapeutic strategies in the treatment of tick borne diseases:
Need for in vivo studies 184
D. Materials and Methods 187
D. 1. Materials and microorganisms 187
D.I.I. Bacterial strains 187
D. 1.1.1. B. burgdorferi isolates 187
D. 1.1.2. E. phagocytophila isolates 187
D.I.1.3. Babesia spp. isolates 187
D.I. 1.4. Reference strains 188
D.I.2. Culture media 188
D. 1.2.1. Modified Barbour Stoenner Kelly (BSK) medium for culturing
B. burgdorferi 188
D.l.2.2. Cell line and culture media used for the propagation of E. phagocytophilalH9
D.l.2.3. HL 60 cell line 189
D.l.2.4. Cell culture medium for the propagation of HL60 cells 189
D.I.2.5. Cell culture medium for the propagation of HL60 cells infected with
E. phagocytophila. 189
D.I.3. Oligonucleotides and antibodies 190
D.I.3.1. Oligonucleotides 190
D.l.3.2. Antibodies 192
D.I .4. Serum sources and patient samples used for the evaluation of
serological diagnostic assay systems 192
D.I.4.1. Serum samples used for the evaluation of a recombinant ELISA (RE) 192
D.l.4.2. Sera used throughout the German LD proficiency testing program 1999
2001 193
D. 1.4.3. Serum samples used for seroepidemiological investigations of anti
E. phagocytophila antibody prevalence in western Germany 193
Contents IX
Page
D. 1.4.4. Serum samples used for seroepidemiological investigations of anti
Babesia spp. antibody prevalence in midwestern Germany 194
D.l.4.5. Other sera used for immunological experiments 195
D. 1.4.5.1. Immune sera from LD patients 195
D.I .4.5.2. Sources of Non immune Human Serum (NHS) 195
D.2. Methods 195
D.2.1. Culture methods 195
D.2.1.1. Culture and propagation of borrelial isolates 195
D.2.1.2. Culture and propagation of HL60 cell line and ehrlichial isolates 196
D.2.1.2.1. Culture and propagation stock cultures of HL60 cells 196
D.2.1.2.2. Propagation of E. phagocytophila isolates 196
D.2.2. Molecular microbiological methods 197
D.2.2.1. Polymerase chain reaction (PCR) methods 197
D.2.2.1.1. PCR for the detection of borrelial gens 197
D.2.2.1.2. RFLP analysisof5S 23S intergenicspacer regionofB. burgdorferi 197
D.2.2.1.3. Reverse transcription polymerase chain reaction (RT PCR) for the
detection of flagellin, OspA, and OspC mRNA 197
D.2.2.1.4. 16S rRNA gene PCR for the universal detection and characterisation
of bacterial pathogens 198
D.2.2.1.5. PCR for the detection of epank gene fragments of E. phagocytophila 198
D.2.2.1.6. PCR for the detection of a species specific region of the 18S rRNA
gene of B. microti 199
D.2.2.1.7. PCR for the detection of a genus specific region of the 18S
rRNA gene of Babesia spp. 199
D.2.2.2. Sequencing of PCR Products 200
D.2.2.3. Restriction analysis using DNA restriction endonucleases 200
D.2.3. Organisation and structure of the German LD proficiency testing
Program 200
X ^__ Contents
Page
D.2.3.1. Preparation and shipment of serum samples 201
D.2.3.2. Assessment of correct test results by reference laboratories 201
D.2.3.3. Study conditions and statistical analysis 202
D.2.4. Serological assays and test procedures 203
D.2.4.1. Development and evaluation of an ELISA (RE) using recombinant
proteins for the serological diagnosis of LD 203
D.2.4.1.1. Preparation of the assay system 203
D.2.4.1.2. Test procedure 203
D.2.4.1.3. Prospective evaluation of the RE in comparison to a conventional whole
cell lysate ELISA 204
D.2.4.2. Other commercial ELISA tests used for serological testing for LD. 204
D.2.4.3. Recombinant immunoblot for serodiagnosis of LD 204
D.2.4.4. Whole ell lysate B. burgdorferi immunoblot for the serodiagnosis of LD205
D.2.4.5. IFA for serological diagnosis of anti is. phagocytophila IgG and
IgM antibodies 205
D.2.4.6. IF As for serological diagnosis of B. microti and B. divergens infection 205
D.2.4.6.1. IFA for serological diagnosis of B. microti infection 205
D.2.4.6.2. IFA for serological diagnosis of A divergens infection 205
D.2.4.6.3. Serological testing for anti Babesia spp. IgM and IgG antibodies 206
D.2.5. Serobiological and protein analytical assays 206
D.2.5.1. In vitro borrelial growth inhibition assay (GIA) 206
D.2.5.2. Determination of total complement activity (CHso) 207
D.2.5.3. Determination of protein concentrations 207
D.2.6. Immune biological detection of borrelial antigens and complement
components 207
D.2.6.1. Detection of deposited C6 and C9 (TCC) 207
D.2.6.2. Detection of deposited complement components on the surfaces of
borreliae by IFA 208
Contents XI
Page
D.2.7. Gel electrophoretic methods and immunobloting of proteins 208
D.2.7.1. Gel electrophoresis of borrelial proteins 208
D.2.7.2. Immunoblotting of proteins 208
D.2.7.3. Immunoblot analysis of immune sera 209
D.2.8. Isolation of borrelial outer membrane fractions 209
D.2.9. In vitro antimicrobial susceptibility testing of B. burgdorferi and
E. phagocytophila against antimicrobial agents 210
D.2.9.1. Antimicrobial drugs and microdilution trays 210
D.2.9.2. Broth microdilution susceptibility testing of B. burgdorferi 210
D.2.9.2.1. Quality control experiments 210
D.2.9.2.2. Determination of test sensitivity 210
D.2.9.2.3. Determination of minimal inhibitory concentration (MIC) 211
D.2.9.2.4. Determination of minimal borreliacidal concentration (MBC) 211
D.2.9.2.5. Time kill studies 211
D.2.9.3. In vitro susceptibility testing of E. phagocytophila 212
D.2.9.3.1. Broth microdilution susceptibility testing 212
D.2.9.3.2. Detection ofehrlichial growth by semiquantitative PCR 212
D.2.9.3.3. Statistical methods for the determination of bacterial growth as
measured by semiquantitative PCR 215
D.2.9.3.4. Preparation of an internal quantitative DNA standard for
E. phagocytophila 217
D.2.9.3.5. Determination of growth kinetics for both tested isolates of
E. phagocytophila 217
D.2.9.3.6. Determination of MIC 217
D.2.9.3.7. Quality control experiments 217
D.2.10. Electron microscope analysis of B. burgdorferi isolates exposed
to antimicrobial agents 218
XII Contents
Page
D.2.11. Analysis of antibiotic exposed borreliae by two dimensional
protein electrophoresis (2 DE) and matrix assisted laser desorption/
ionisation time of flight mass spectrometry (MALDI TOF MS) 218
D.2.11.1. Broth micro and macrodilution susceptibility testing of borrelial cells 218
D.2.11.2. Preparation of protein samples 219
D.2.11.3. Two dimensional electrophoresis (2 DE) and staining conditions 219
D.2.11.4. Scanning and spot detection 219
D.2.11.5. Identification of proteins by MALDI TOF MS 220
D.2.12. Statistics 220
E. Summary and conclusion 221
F. References 225
G. List of abbreviations 255
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id | DE-604.BV020023349 |
illustrated | Illustrated |
indexdate | 2024-07-09T20:11:04Z |
institution | BVB |
isbn | 3832233474 |
language | English |
oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-013344688 |
oclc_num | 62309145 |
open_access_boolean | |
owner | DE-355 DE-BY-UBR |
owner_facet | DE-355 DE-BY-UBR |
physical | XII, 256 S. Ill., graph. Darst. |
publishDate | 2004 |
publishDateSearch | 2004 |
publishDateSort | 2004 |
publisher | Shaker |
record_format | marc |
series | Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main |
series2 | Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main |
spelling | Hunfeld, Klaus-Peter Verfasser aut Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens Klaus-Peter Hunfeld Aachen Shaker 2004 XII, 256 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main 2 Babesia Borrelia Ehrlichia Microbial Sensitivity Tests Microbial sensitivity tests Seroepidemiologic Studies Tick-Borne Diseases Tick-borne diseases Epidemiology Ehrlichia (DE-588)4259661-0 gnd rswk-swf Serodiagnostik (DE-588)4181044-2 gnd rswk-swf Babesia divergens (DE-588)4541420-8 gnd rswk-swf Sensibilität (DE-588)4054554-4 gnd rswk-swf Antimikrobieller Wirkstoff (DE-588)4142688-5 gnd rswk-swf Epidemiologie (DE-588)4015016-1 gnd rswk-swf Borrelia burgdorferi (DE-588)4290954-5 gnd rswk-swf Borrelia burgdorferi (DE-588)4290954-5 s Serodiagnostik (DE-588)4181044-2 s Epidemiologie (DE-588)4015016-1 s DE-604 Babesia divergens (DE-588)4541420-8 s Ehrlichia (DE-588)4259661-0 s Antimikrobieller Wirkstoff (DE-588)4142688-5 s Sensibilität (DE-588)4054554-4 s Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main 2 (DE-604)BV019831889 2 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=013344688&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Hunfeld, Klaus-Peter Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens Schriften aus dem Institut für Medizinische Mikrobiologie des Klinikums der Johann-Goethe-Universität Frankfurt am Main Babesia Borrelia Ehrlichia Microbial Sensitivity Tests Microbial sensitivity tests Seroepidemiologic Studies Tick-Borne Diseases Tick-borne diseases Epidemiology Ehrlichia (DE-588)4259661-0 gnd Serodiagnostik (DE-588)4181044-2 gnd Babesia divergens (DE-588)4541420-8 gnd Sensibilität (DE-588)4054554-4 gnd Antimikrobieller Wirkstoff (DE-588)4142688-5 gnd Epidemiologie (DE-588)4015016-1 gnd Borrelia burgdorferi (DE-588)4290954-5 gnd |
subject_GND | (DE-588)4259661-0 (DE-588)4181044-2 (DE-588)4541420-8 (DE-588)4054554-4 (DE-588)4142688-5 (DE-588)4015016-1 (DE-588)4290954-5 |
title | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens |
title_auth | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens |
title_exact_search | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens |
title_full | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens Klaus-Peter Hunfeld |
title_fullStr | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens Klaus-Peter Hunfeld |
title_full_unstemmed | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens Klaus-Peter Hunfeld |
title_short | Contributions to Seroepidemiology, Diagnosis, and Antimicrobial Susceptibility of Borrelia, Ehrlichia, and Babesia as Indigenous Tick-conducted Pathogens |
title_sort | contributions to seroepidemiology diagnosis and antimicrobial susceptibility of borrelia ehrlichia and babesia as indigenous tick conducted pathogens |
topic | Babesia Borrelia Ehrlichia Microbial Sensitivity Tests Microbial sensitivity tests Seroepidemiologic Studies Tick-Borne Diseases Tick-borne diseases Epidemiology Ehrlichia (DE-588)4259661-0 gnd Serodiagnostik (DE-588)4181044-2 gnd Babesia divergens (DE-588)4541420-8 gnd Sensibilität (DE-588)4054554-4 gnd Antimikrobieller Wirkstoff (DE-588)4142688-5 gnd Epidemiologie (DE-588)4015016-1 gnd Borrelia burgdorferi (DE-588)4290954-5 gnd |
topic_facet | Babesia Borrelia Ehrlichia Microbial Sensitivity Tests Microbial sensitivity tests Seroepidemiologic Studies Tick-Borne Diseases Tick-borne diseases Epidemiology Serodiagnostik Babesia divergens Sensibilität Antimikrobieller Wirkstoff Epidemiologie Borrelia burgdorferi |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=013344688&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
volume_link | (DE-604)BV019831889 |
work_keys_str_mv | AT hunfeldklauspeter contributionstoseroepidemiologydiagnosisandantimicrobialsusceptibilityofborreliaehrlichiaandbabesiaasindigenoustickconductedpathogens |