Evaluation of the Indirect Effects of Rotavirus Vaccination Programs in World Health Organization Member States Open Access

Chaney, Danielle (Spring 2022)

Permanent URL: https://etd.library.emory.edu/concern/etds/707958983?locale=en%5D
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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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