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List of abbreviations...7

Abstract...8

List of papers and contributions of the candidate...12

CHAPTER 1: GENERAL INTRODUCTION...14

Background...15

Geopolitical background information...17

Socio-demographic data...17

Organization of health services delivery system...17

Vaccine Preventable Diseases Program, Organization and functionality...20

Immunization coverage as per DHS 2010...21

CHAPTER 2: CURRENT STATE OF KNOWLEDGE AND OVERVIEW OF ROTAVIRUS DISEASE AND VACCINE...24

Current state of knowledge about rotavirus diseases and vaccines...25

Rotarix®...26

RotaTeq

®

...27

Progress for new live-attenuated, oral rotavirus licensed vaccines...27

Rotavac

®

...28

Lanzhou institute of biological products, China...28

Center for research and production of vaccines (PolyVac), Vietnam...30

Rotavirus vaccine and intussusception...30

Circulating rotavirus strains...32

CHAPTER 3: JUSTIFICATION, OBJECTIVE and PROCEDURES/METHODS...34

Context and justification...35

Research Question and objectives...36

Research question 1...36

Research question 2...36

Research question 3...36

Research question 4...36

Research question 5...36

Research objectives...37

General objective...37

Specific objectives...37

Procedures and methods...37

Design...37

Description and source of participants...39

Case definition and inclusion criteria...39

Case exclusion criteria...41

Justification of exclusion of any sub-segment of the population...41

Sampling, including sample size and statistical power...42

Methods...42

Trends in diarrhea hospitalizations...42

Trends in rotavirus-specific hospitalizations and changes in rotavirus epidemiology ...43

Enrollment...43

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Consent Process...44

Variables...44

Data Analysis Plan...45

Data entry, editing, and management...46

Statistical Analysis...46

Ethical review...47

References Background/Hypotheses/Objectives and Methods...48

CHAPTER 4 : RESULTS...53

Result 1: Can Routinely Collected National Data on Childhood Morbidity and Mortality from Diarrhea be Used to Monitor Health Impact of Rotavirus Vaccination in Africa? – Examination of Pre-Vaccine Baseline Data from Rwanda...54

Result 2: The economic burden attributable to a child’s inpatient admission for diarrheal disease in Rwanda...60

Result 3: A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda...76

Result 4: Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhea and rotavirus in children in Rwanda: a time-series analysis...84

Result 5: Rotavirus Strains Circulating in Rwanda Directly Before and After the Introduction of RotaTeq Vaccine: 2011 to 2013...93

CHAPTER 5: DISCUSSIONS, GENERAL CONCLUSION AND PERSPECTIVES...108

Discussions...109

Links between the five papers:...114

Conclusion, implications and recommendations...116

Perspectives...118

Perspectives for research...118

Perspectives for policy implication...119

References...120

GENERAL REFERENCES...123

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