Invasive Haemophilus influenzae type b disease in German children [Elektronische Ressource] : epidemiology and vaccine effectiveness in the era of hexavalent vaccines / vorgelegt von Helen Kalies

Helen Kalies

Sujets

• Gesundheit

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2007
• Nombre de lectures: 41
• Langue: Deutsch

Extrait

Aus der Abteilung für Epidemiologie im Kindes- und Jugendalter,
Schwerpunkt Gesundheitsforschung
Abteilungsleiter: Prof. Dr. Rüdiger von Kries, MSc

Institut für soziale Pädiatrie und Jugendmedizin
Vorstand: Prof. Dr. Dr. Hubertus von Voss

der Ludwig-Maximilians-Universität München






Invasive Haemophilus influenzae type b
disease in German children:

Epidemiology and vaccine effectiveness in
the era of hexavalent vaccines







Dissertation
zum Erwerb des Doktorgrades der Humanbiologie
an der Medizinischen Fakultät der
Ludwig-Maximilians-Universität zu München


vorgelegt von


Dipl. biol. Helen Kalies, M.P.H.

aus London


2007











Mit Genehmigung der Medizinischen Fakultät
der Universität München










Berichterstatter: Prof. Dr. R. von Kries, MSc
2. Berichterstatter Priv. Doz. Dr. U. Wintergerst

Mitberichterstatter: Prof. Dr. J. Haas
Prof. Dr. Heesemann


Dekan: Prof. Dr. med. D. Reinhardt


Tag der mündlichen Prüfung: 05.02.2007



CONTENTS

1 SUMMARY (ENGLISH)............................................................................................1
2 SUMMARY (GERMAN)3
3 INTRODUCTION ......................................................................................................5
4 OBJECTIVES OF THE STUDY ...............................................................................7
5 STRUCTURE OF THE DOCUMENT........................................................................8
6 MATERIAL AND METHODS ...................................................................................9
6.1 DEFINITIONS...............................................................................................................9
6.1.1 Recommended Hib vaccination schedule........................................................9
6.1.2 Categories of vaccination status......................................................................9
6.1.3 Vaccine failures .............................................................................................10
6.2 H. INFLUENZAE CASES IN GERMANY ..........................................................................11
6.2.1 Case definition ...............................................................................................11
6.2.2 ‚Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland’
(ESPED).........................................................................................................11
6.2.2.1 Clinical ESPED ...........................................................................................12
6.2.2.2 Laboratory ESPED .....................................................................................12
6.2.2.3 Matching of the two sources and identification of the duplicates................13
6.2.2.4 Serotyping and final classification...............................................................14
6.3 NATIONAL IMMUNISATION SURVEY .............................................................................14
6.4 DATA ANALYSIS ........................................................................................................18
6.4.1 Incidence rates ..............................................................................................18
6.4.2 Survival analysis for uptake and timing of immunisations .............................18
6.4.3 Adjustments for underreporting and proportion serotyped ............................19
6.4.3.1 Adjustment for underreporting of Hi cases through the reporting
systems.......................................................................................................19
6.4.3.2 Adjustment for differences in the proportion of typed cases over time .......20
6.4.4 Vaccine effectiveness ....................................................................................20
6.4.4.1 Theory.........................................................................................................21
6.4.4.2 Hib vaccine effectiveness ...........................................................................22
6.4.4.3 Sensitivity analysis......................................................................................26
7 RESULTS...............................................................................................................27
7.1 DATA QUALITY..........................................................................................................27
7.1.1 ESPED surveillance system ..........................................................................27
7.1.1.1 Response rates...........................................................................................27
7.1.1.2 Completeness of case reporting .................................................................28
7.1.1.3 Proportion of cases typed29
7.1.1.4 Serotyping: concordance between local and reference laboratories ..........30
7.1.2 National immunisation survey........................................................................31
7.1.2.1 Response rates and data validity................................................................31
7.1.2.2 Representativeness ....................................................................................31
7.2 GENERAL DESCRIPTION OF THE DATA35
7.2.1 H. influenzae cases 2001-2004 .....................................................................35
7.2.1.1 Seasonal distribution ..................................................................................35
7.2.1.2 Distribution by age, sex and nationality ......................................................35
7.2.1.3 Clinical description......................................................................................36
7.2.1.4 Serotypes....................................................................................................37
7.2.1.5 Vaccination status.......................................................................................38
7.2.2 Immunisation status of children in the German population............................39
7.2.2.1 Hib vaccine coverage .................................................................................39
7.2.2.2 Use of hexavalent vaccines ........................................................................43
7.2.2.3 Timeliness of hexavalent vaccine uptake ...................................................43
7.3 ANNUAL NUMBERS OF HIB CASES AND VACCINE FAILURES BEFORE AND AFTER
LICENSURE OF HEXAVALENT VACCINES (OBJECTIVE 1)...............................................45
7.3.1 Annual numbers of Hib cases45
7.3.2 Vaccine failures .............................................................................................47
7.4 ANNUAL INCIDENCE RATES OF H. INFLUENZAE CASES BEFORE AND AFTER
LICENSURE OF HEXAVALENT VACCINES (OBJECTIVE 2)50
7.4.1 H. influenzae..................................................................................................50
7.4.2 e type b .......................................................................................50
7.4.3 Non-type b H. influenzae ...............................................................................51
7.4.4 Adjusted incidence rates................................................................................52
7.5 EFFECTIVENESS OF HEXAVALENT VACCINES AGAINST INVASIVE HIB DISEASE
(OBJECTIVE 3)..........................................................................................................54
7.5.1 Cases and subcohort members contributing to effectiveness calculations....54
7.5.1.1 Cases54
7.5.1.2 Subcohort ...................................................................................................55
7.5.2 Estimates of hexavalent Hib vaccine effectiveness .......................................57
7.5.2.1 Vaccine effectiveness for completeness of the vaccination schedule ........57
7.5.2.2 r age-eligibility of the vaccination..........57
7.5.3 Sensitivity analyses .......................................................................................58
8 DISCUSSION .........................................................................................................59
8.1 H. INFLUENZAE TYPE B DISEASE BEFORE AND AFTER THE INTRODUCTION OF
HEXAVALENT COMBINATION VACCINES.......................................................................59
8.1.1 Cases and incidences....................................................................................59
8.1.2 Vaccine failures .............................................................................................60
8.1.3 Possible biases..............................................................................................60
8.2 EFFECTIVENESS OF HEXAVALENT VACCINES AGAINST INVASIVE HIB DISEASE ..............62
8.2.1 Superiority of case-cohort design ..................................................................63
8.2.2 Possible biases64
8.2.3 Causes for differing vaccine effectiveness estimates between UK and
Germany