Evaluation of the Indirect Effects of Rotavirus Vaccination Programs in World Health Organization Member States Público
Chaney, Danielle (Spring 2022)
Abstract
Rotavirus is a leading cause of diarrhea-related deaths in children under 5 years old, most of which occur in low-to-middle income countries (LMICs). Licensed rotavirus vaccines provide high levels of direct protection, but their indirect effect – the protection provided to unvaccinated individuals within a mixed-vaccinated population – is not fully understood. We aimed to quantify the population-level effects of rotavirus vaccination and identify factors that drive indirect protection. We used a transmission model to estimate the indirect effects of vaccination on rotavirus deaths in 112 LMICs. Indirect effects were estimated by quantifying the difference between predicted impacts if vaccination did (overall effects) or did not (direct effects) change the force of infection, and both scenarios were compared with a no vaccine scenario. We performed a linear regression analysis on model outputs to identify predictors of indirect effect magnitude. We also used logistic regression to understand predictors of negative indirect effects. Indirect effect sizes 8-years post-vaccine introduction ranged from 16.9% in the WHO European region to 0.97% in the Western Pacific region. Under-5 mortality rate and vaccine coverage were positively associated with indirect effect magnitude. Birth rate was negatively correlated. Of the 112 countries analyzed, 18 (16%) had at least one year with a predicted negative indirect effect. Negative indirect effects were more common in countries with higher birth rate and were less common in countries with higher under-5 mortality and higher vaccine coverage. These results suggest that the rotavirus vaccine provides indirect benefits to unvaccinated individuals within a partially-vaccinated population. The strength of this effect varies by country and depends on country-specific birth rate, under-5 mortality rate, and vaccine coverage. Rotavirus vaccination may have a larger impact than would be expected from direct effects alone.
Table of Contents
CHAPTER 1: INTRODUCTION 1
INTRODUCTION AND RATIONALE 1
PROBLEM STATEMENT 1
RESEARCH AIMS 2
SIGNIFICANCE STATEMENT 2
CHAPTER 2: LITERATURE REVIEW 3
THEORY OF DIRECT AND INDIRECT VACCINE EFFECTS 3
OVERVIEW OF ROTAVIRUS BIOLOGY AND EPIDEMIOLOGY 5
DIRECT AND INDIRECT EFFECTS OF ROTAVIRUS VACCINES 6
CHAPTER 3: MANUSCRIPT 10
ABSTRACT 11
INTRODUCTION 12
METHODS 13
Demographic Factors of World Health Organization (WHO) Geographic Regions 13
Emory Rotavirus Model 15
Vaccine Effect Estimates 16
Predictors of the Magnitude of Indirect Effects 16
Predictors of the Negative of Indirect Effects 17
Ethical Considerations 17
RESULTS 17
Estimation of Vaccine Effects by WHO Geographic Region 17
Predictors of Indirect Effect Magnitude 18
Predictors of Negative Indirect Effect 19
DISCUSSION 20
Summary of Key Findings 20
Indirect Vaccine Effects Trends by Geographic Region 21
Predictors of Indirect Effect Magnitude 21
Predictors of Negative Indirect Effect 23
Study Limitations 24
CONCLUSION 25
TABLES AND FIGURES 26
CHAPTER 4: CONCLUSIONS AND IMPLICATIONS 35
REFERENCES 36
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