Table Of ContentChlamydia pneumoniae and Chronic Diseases
Springer-Verlag Berlin Heidelberg GmbH
JOHANNA L'AGE-STEHR (ED.)
Chlamydia pneumoniae
and Chronic Diseases
Proceedings of the State-of-the-Art Workshop
held at the Robert Koch-Institut Berlin
on 19 and 20 March 1999
Springer
Editor:
DR. JOHANNA L'AGE-STEHR
Robert Koch-Institut
Nordufer 20
13353 Berlin
ISBN 978-3-540-41136-9
CIP data applied for
Chlamydia pneumoniae and chronic diseases : proceedings of the state-of-the-art workshop held at
the Robert Koch-Institut Berlin on 19 and 20 March 1999 / Johanna L'age-Stehr (ed.). - Berlin ;
Heidelberg ; New York ; Barcelona ; Hong Kong ; London ; Milan ; Paris ; Singapore ; Tokyo :
Springer, 2000
ISBN 978-3-540-41136-9 ISBN 978-3-642-57195-4 (eBook)
DOI 10.1007/978-3-642-57195-4
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v
Preface
J. L 'age-Stehr
In March 1999 international experts from many fields gathered in Berlin for a
State-of-the-Art Workshop on Chlamydia pneumoniae and chronic diseases. This
workshop was the first of its kind initiated and organized by the Robert Koch
Institut.
The objectives of the workshop were to discuss and enhance interdisciplinary
knowledge on the possible etiological role of Chlamydia pneumoniae, a wide
spread human respiratory infection, in the pathogenesis of chronic inflammatory
diseases with major public health impact such as
- atherosclerosis,
- cardiovascular disease,
- adult-onset asthma bronchiale,
- chronic obstructive pulmonary disease,
- reactive arthritis,
- Morbus Alzheimer and
- Multiple Sclerosis.
An association of Chlamydia pneumoniae infections and atherosclerosis has
been indicated by serological methods and by detection of the agent in vascular
tissues. Major goals of this workshop were to identify current deficiencies in
knowledge and research approaches, quality of methodologies used for detection
of the infection, designs of epidemiological studies and to encourage prioritization
of approaches in basic, applied and clinical research in a collaborative, multidisci
plinary and multicenter effort.
Some of the experimental evidence put forward to the audience by the experts
supported the hypothesis that recurrent or chronic persistent and reactivated
Chlamydia pneumoniae infections may be risk factors in atherogenesis and the
development of cardiovascular disease, in asthma bronchiale of adult onset and
chronic obstructive pulmonary disease.
Evidence that these infections initiate, perpetuate or accelerate these major dis
eases when combined with other risk factors was vividly discussed as well as were
the goals of future research. The possible involvement of Chlamydia pneumoniae
in the pathogenesis of neurological diseases such as Morbus Alzheimer and Mul
tiple Sclerosis met with considerable skepticism.
On the basis of current knowledge the following goals for future basic and
applied research have been identified:
- encouragement and promotion of international multicenter, multidisciplinary
collaborations of clinical and basic researchers for development and application
of standardized noninvasive diagnostic tools for the detection of chronic Chla
mydia pneumoniae infections,
VI
- analysis of the influence of host genetics, classical identified risk factors and
different agent-host interactions on susceptibility to chronic, recurrent or reac
tivated Chlamydia pneumoniae infections and the development of chronic dis
eases,
- search for surrogate diagnostic markers for chronic inflammation by Chlamydia
pneumoniae infections to develop better diagnostic strategies that would iden
tify subpopulations of patients at risk for cardiovascular diseases which would
profit from antimicrobial therapy,
- promotion of more basic research on the natural history and pathogenicity of
chronic, persistent and reactivated Chlamydia pneumoniae infections,
- inclusion of better standardized and expanded diagnostic strategies in design
and monitoring of epidemiological cohort and case control studies,
- encouragement to develop better antimicrobial agents and therapeutic strategies
and regimens (e.g. combinations of antibiotics) to increase treatment efficacy in
subpopulations of chronic diseased patients with chronic, reactivated or remit
tent Chlamydia pneumoniae infections and use of more standardized diagnostic
methodology to monitor efficacy of antimicrobial therapy in selected groups of
patients.
All comments and questions in response to individual presentations have been
enclosed in these proceedings to give the readers interested in the field of Chla
mydia pneumoniae and chronic diseases a life-like picture of the often diverse
opinions of the experts.
VII
Introduction - R. Kurth ......................................................................................... 1
Chapter 1
Biology, Immunology and Pathology of
Chlamydia Pneumoniae Infections
1.1 Pathogenic mechanisms of chronic Chlamydia infections
E. Straube, J. Radel ........................................................................................... 3
1.2 Biology, immunology and persistence of Chlamydia pneumoniae:
Links to chronic disease
G./. Byrne and M. V. Kalayoglu ......................................................................... 8
Chronic chlamydial diseases: C. pneumoniae and atherosclerosis .................... 9
Chlamydial Hsp60 and the chronic disease process ........................................ 10
Summary ......................................................................................................... 11
1.3 Animal models for Chlamydia pneumoniae infection
M. Leinonen and P. Saikku .............................................................................. 19
Monkey models for C. pneumoniae infection ................................................. 19
Mouse models for C. pneumoniae infection .................................................... 19
Rabbit model for C. pneumoniae infection ...................................................... 20
Animal models for C. pneumoniae-associated atherosclerosis ........................ 20
Conclusions ............................................................................... ~ ..................... 21
1.4 Molecular biology and serodiagnostics of Chlamydia pneumoniae -
potential way to a vaccine
G. Christiansen, A.S. Madsen, T. Boesen, K. Hjem¢, L. Daugaard,
K. Knudsen, P. Mygind, S. Birkelund .............................................................. 25
Introduction ..................................................................................................... 25
The GGAI gene family .................................................................................... 25
Migration of GGAI proteins in SDS-PAGE .................................................... 27
Antigenicity of GGAI proteins ........................................................................ 27
Immunoblotting with human sera .................................................................... 28
Conclusion and considerations for future work ............................................... 29
Chapter 2
DiagnosiS of Chlamydia pneumoniae Infections
2.1 Direct detection of Chlamydia pneumoniae in atherosclerotic
plaques
M. Maass ......................................................................................................... 33
Introduction ..................................................................................................... 33
Immunohistochemistry .................................................................................... 35
PCR ................................................................................................................. 35
Cell Culture ..................................................................................................... 37
Conclusion ....................................................................................................... 37
VIII
2.2 Detection of Chlamydia pneumoniae DNA in white blood cells
1. Boman .......................................................................................................... 42
2.3 Detection of Chlamydia pneumoniae in clinical specimens
byPCR-EIA
C.A. lantos ...................................................................................................... 48
2.4 State of the art in the diagnosis of acute and chronic Chlamydia
pneumoniae infection
M.R. Hammerschlag ........................................................................................ 52
Culture of C. pneumoniae ............................................................................... 52
Detection of antibody to C. pneumoniae in serum .......................................... 53
Chapter 3
Chronic Diseases Possibly Associated with
Chlamydia pneumoniae Infections
3.1 Epidemiological data on respiratory tract infection with
Chlamydia pneumoniae and clinical complications
1. Boman ........................................................... 63
i ..............................................
3.2 Role of C. pneumoniae in severe asthma and COPD:
Epidemiology and treatment
R. Cosentini, F. Blasi ....................................................................................... 68
Asthma ............................................................................................................ 68
Chronic bronchitis ........................................................................................... 69
3.3.1 Chlamydia pneumoniae in atherosclerosis
P. Saikku ......................................................................................................... 73
Introduction ..................................................................................................... 73
Epidemiological and seroepidemiological findings ......................................... 73
Histopathological studies ................................................................................. 74
Intervention trials ............................................................................................ 74
Possible pathogenetic mechanisms by which an infection could affect
the development of atherosclerosis and coronary heart disease .................... 75
Conclusions ..................................................................................................... 76
3.3.2 Prevalence of Chlamydia pneumoniae in human coronary
plaques with acute coronary syndrome
G. Bauriedel, U. Welsch and B. Liideritz ........................................................ 84
Introduction ..................................................................................................... 84
Patients and methods ....................................................................................... 85
Results ............................................................................................................. 85
3.3.3 Chlamydiallipopolysaccharide and atherosclerosis
H. Brade .......................................................................................................... 91
3.3.4 Clinical trial designs to study antibiotic intervention in
atherosclerosis
M. Dunne ......................................................................................................... 97
IX
3.3.5 Why antibiotics against Chlamydia pneumoniae for
treatment of atherosclerotic disease could fail
1.M. Ossewaarde ........................................................................................... 103
3.3.6 Atherosclerosis: Why the search for a causative
infectious agent is not warranted
S. Bhakdi ........................................................................................................ 108
3.4 Chlamydia infections and arthritis
1. Sieper ......................................................................................................... 112
3.5 Chlamydia pneumoniae, APOE genotype, and Alzheimer's
disease
A.P. Hudson, H.e. Gerard, 1.A. Whittum-Hudson, D.M. Appelt,
B.l. Balin ....................................................................................................... 121
Alzheimer's disease ....................................................................................... 12 1
APOE allele types and Alzheimer's disease .................................................. 122
Pathogenesis and epidemiology of Chlamydia pneumoniae ......................... 122
Chlamydia pneumoniae DNA in the Alzheimer's brain ................................ 123
Ultrastructural analysis of Chlamydia pneumoniae in the
Alzheimer's brain ........................................................................................ 124
Culture of Chlamydia pneumoniae from Alzheimer's brain tissue ............... 126
Immunohistochemical analyses ..................................................................... 126
Chlamydia pneumoniae infection and APOE allele types ............................. 128
Future research directions .............................................................................. 128
3.6 Association of Chlamydia pneumoniae with Multiple Sclerosis:
Protocol for detection of C. pneumoniae in the CSF and summary
of preliminary results
e. W. Stratton, S. Sriram, S. fao, A. Tharp, L. Ding, J.D. Bannan,
W.M. Mitchell ................................................................................................ 137
Introduction ................................................................................................... 137
Materials and methods ................................................................................... 137
Results ........................................................................................................... 143
Discussion ..................................................................................................... 148
Chapter 4
Epidemiology and Public Health Impacts of
Chlamydia pneumoniae Infections
4.1 Trends and variations of chronic diseases in populations -
Can infectious agents help to solve the puzzles?
H.W. Hense .................................................................................................... 153
x
4.2 The epidemiology of Chlamydia pneumoniae versus the
epidemiology of potential Chlamydial diseases (Atherosclerosis,
Multiple Sclerosis, M. Alzheimer)
W Stille, C. Stephan, M Madeo, E. Bauer-Krylov ......................................... 163
Epidemiology of Chlamydia pneumoniae ...................................................... 163
Seroepidemiology ........................................................................................... 163
Epidemiology of Multiple Sclerosis ............................................................... 167
Epidemiology of Alzheimer's Disease ........................................................... 168
Conclusion ...................................................................................................... 168
4.3 The high male mortality of coronary heart diseases can be
explained as a result of chronic infection
E. Bauer-Krylov, W. Stille .............................................................................. 171
4.4 The Spandauer Gesundheitstest - Retrospective cohort study
on Chlamydia pneumoniae infections and cardiovascular disease -
A study concept
T Ziese ............................................................................................................ 178
Introduction .................................................................................................... 178
Study goals ..................................................................................................... 178
Study outline ................................................................................................... 178
4.5 Public health impact of atherosclerosis and Chlamydia pneumoniae
infections - What do we know and what to expect from future research
JM Ossewaarde ............................................................................................ 184
Introduction .................................................................................................... 184
Epidemiology of cardiovascular diseases in the Netherlands ......................... 184
Epidemiology of Chlamydia pneumon iae infections ...................................... 185
Respiratory tract infections as a risk factor for cardiovascular disease .......... 186
Association of C. pneumoniae infections and cardiovascular diseases ........... 186
Public health consequences ............................................................................ 187
Conclusions .................................................................................................... 187
Chapter 5
Final Discussion: Pro and Contra the
Role of Chlamydia pneumoniae in Chronic Diseases ....... 193
