Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.2 Scientific background and rationale for study elements
the same time, substantial immunization gaps still exist among German adults 378, 379 . The
impact of both childhood and adult vaccination strategies on the epidemiology of vaccinepreventable
diseases has become an emerging topic in mathematical vaccination models.
For instance, attempts to describe latency and reactivation of shingles after varicella virus
infection may have paramount implications for varicella vaccination strategies, but validation
through prospective study designs is urgently needed 380 . Similar questions concerning
replacement, reactivation, and recombination of other pathogens such as Streptococcus
pneumonia, Neisseria meningitidis, and human papillomavirus, and the respective impact
of these effects, can only be addressed adequately in prospective settings. Seromarkers
for immunity exist for most vaccine-preventable diseases and will be complemented by a
review of immunization cards, self-report, and secondary data analysis such as data available
through the Associations of Statutory Health Insurance Physicians 381 .
Effects of infections and immunizations on cancer and other chronic diseases: A variety of
pathogens have been associated with increased risk of malignancies, such as Helicobacter
pylori and gastric cancer and mucosal-associated lymphoid tissue lymphoma, human papilloma
virus and cervical cancer, and hepatitis viruses and liver cancer and, recently, lymphoma
382 . The attributable risk of forms of cancer stemming from these treatable and partly
vaccine-preventable infections has been estimated by the American Cancer Society to be
about 18% worldwide. The 5-year prevalence of cervical cancer in Germany is 23,800, with
1,600 deaths annually according to the Germany cancer registry 137 . The fraction of these
cancers truly attributable to infections, however, can only be validly estimated by using a
prospective study design. The National Cohort provides the suitable age distribution and
study design to address these questions, as a large variety of infections can be assessed
through seroconversion markers, while direct pathogen detection may also be possible in
level 3 studies.
Persistent infections, particularly by members of the herpesvirus family, have been associated
with increased overall mortality and with the pathogenesis of various chronic diseases
that often feature some degree of chronic inflammation 383, 384 . Human cytomegalovirus has
been linked to heart disease and other cerebrovascular diseases, including stroke 385 , autoimmune
diseases, certain cancers (e.g., glioblastoma multiforme), and to immune senescence.
With a baseline seroprevalence of 30% and a yearly seroconversion rate of
0.55% 386 , this virus is well suited for prospective investigations into effects of a specific
pathogen on the incidence of chronic diseases. There is epidemiologic evidence that infectious
agents contribute to the pathogenesis of neurodegenerative and neuroinflammatory
diseases, including Alzheimer’s disease and multiple sclerosis 387 . However, a single pathogen
has not been identified. By prospectively collecting information on chronic disease endpoints
and a variety of biomaterials from each participant, the etiology of these and other
chronic diseases can be investigated in the context of (1) complex infectious exposure both
cross-sectionally and longitudinally (sequential infections) and (2) currently unknown or unsuspected
infectious exposure.
Assessment of immunization and infection status:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire, immunization cards
Level 3: Seromarkers
Immune senescence, immune dysfunction and chronic disease risk
Immune senescence refers to the increased susceptibility to infections, poor vaccine responses,
and altered chronic inflammation that is observed in about 10–30% of individu-
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A.2