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

A.2
A.2. Scientific background and rationale for study elements
Hepatitis B and C virus infection, HIV infection, and tuberculosis will not be studied in the
National Cohort due to low and declining incidence.
Recurrent respiratory infections are diseases characterized by high frequency of occurrence
and high associated economic costs. An adult on average may suffer from two
symptomatic respiratory tract infections per year 131 . Risk factors for an increased frequency
of respiratory infections include sex 132 , older age 133 , occupational exposures 134 , animal contact,
number and type of social contacts, including children in the household 135 , or lifestyle
factors (smoking, physical inactivity) and nutritional status 136 . Genetic factors have been
identified in the context of the relatively rare, defined immunodeficiency syndromes of adulthood
(e.g., common variable immunodeficiency), but factors determining milder phenotypes
in the general population remain largely unknown. We will determine the frequency, type
(upper vs. lower respiratory tract), and severity (antibiotic use, work-related absenteeism,
physician visits, hospitalization, complications, and need for intensive care) of respiratory
infections (not of specific pathogens) and also include these endpoints in the models for
changes in immune and pulmonary function over time. A combination of these items will be
used to compute a respiratory infection risk score. By applying the score at each follow-up
we can prospectively assess susceptibility to respiratory infections. Endpoints will be assessed
through a combination of interview and active surveillance with modern communication
methods. In the interview, respiratory infections will be defined according to symptombased,
validated measurement instruments.
Assessment of recurrent respiratory infections:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire; respiratory infection risk score
Level 3: Active surveillance
Recurrent gastrointestinal infections: A wide range of bacterial (e.g., Campylobacter, Salmonella,
Yersinia enterocolitica), viral (e.g., norovirus, rotavirus), and parasitic (e.g., Giardiasia)
pathogens cause acute gastrointestinal infections. These infections are still very common
in Germany. For example, about 235,000 cases of acute gastrointestinal infections due
to Campylobacter, Salmonella, rotavirus and norovirus were reported to the Robert Koch
Institute in 2009 137 , and these notified cases represent a minor portion of the true disease
burden as demonstrated in the Netherlands 138 , the UK 139 , and Denmark 140 . Specifically, in a
Dutch cohort study, the ratio of cases observed by active follow-up as compared to notifications
to a national surveillance system was 3:1 for Salmonella, 8:1 for Campylobacter, 35:1 for
rotavirus, and 1500:1 for norovirus 138 . Known risk factors for acute gastrointestinal infections
include sex, age, urban/rural place of residence, SES, and behavioral factors such as dietary
habits or contact with animals. However, factors that determine the course and severity of
acute gastrointestinal infections are still largely unknown. There is evidence that genetic host
factors determine susceptibility for norovirus infection 141 . Definitions for syndromic screening
questions for acute gastrointestinal infections are well established 142 and will be combined
with modern communications tools (e.g., text message recall) for further follow-up. At Level 3
of the cohort, those who report episodes of acute gastrointestinal infections by modern communication
tools will be asked to return stool samples by mail. This method has been used
successfully in prospective studies in Germany 143 , the UK 142 , and the Netherlands 138 .
Assessment of recurrent gastrointestinal infections:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire
Level 3: Active surveillance; collection of stool samples during acute
infection
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