Targeting Enteric and Respiratory Viruses Across Scales: The Impact of Immunization, Exposure Control, and Environmental Change on Population Disease Dynamics Restricted; Files Only

Sajewski, Elizabeth (Summer 2022)

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Enteric and respiratory viruses represent the leading causes of infectious disease globally. Public health interventions including vaccination and exposure control can limit viral transmission while environmental changes drive disease dynamics across regions. In this dissertation, we consider (1) the impact of pediatric vaccination on population norovirus burden, (2) the effects of vaccination and exposure control in limiting SARS-CoV-2 transmission among essential food workers, and (3) the influence of urbanization on diarrheal disease seasonality.

Norovirus is the leading cause of acute gastroenteritis across age groups worldwide. In Aim 1, we compared the impact of pediatric norovirus vaccination by vaccination schedule on population norovirus burden. Using an age-structured deterministic compartmental model of norovirus transmission and vaccination, we simulated five pediatric vaccination schedules (0/2/4m, 2/4/6m, 6/12m, 12/24m, 48m). We found that the 2/4/6m vaccination schedule reduced norovirus cases in children (<5 years of age) by up to 43% and across the total population by 19%, with 38% of the total impact conferred by indirect effects.

The SARS-CoV-2 pandemic continues to pose a significant global health threat. In Aim 2, we developed a novel quantitative microbial risk assessment-infectious disease transmission model to evaluate the use of vaccination alone and in combination with non-pharmaceutical interventions (masking, physical distancing, testing) in limiting the transmission of SARS-CoV-2. Applying this model to a 50-person food manufacturing facility, we found that high efficacy masks (double masking or N95 masks), daily testing, or combined vaccination (60% coverage) and universal masking, was sufficient to effectively protect essential food workers.

Environmental change can also significantly impact transmission and shift disease ecology and etiology. In Aim 3, we evaluated the impact of urbanicity and urbanization on the seasonality of diarrheal disease in Sichuan, China, a setting with limited vaccination for enteric pathogens and rapid urbanization. In this context, we found that increasing urbanicity was associated with decreased diarrheal disease, with effect varying by month, and the relationship between urbanization and diarrheal disease was dependent on underlying urbanicity and month of the year.

Ultimately, the optimal interventions to control viral transmission depend on many factors across scales, from viral characteristics to environmental change. Using modeling methods such as those demonstrated in this dissertation can support better understanding of disease dynamics and the best-suited interventions to alter them. 

Table of Contents

1 Introduction 1

1.1 Aim 1: Pediatric Norovirus Vaccination 4

1.1.1 Norovirus Burden 4

1.1.2 Norovirus Transmission Pathways and Disease Progression 5

1.1.3 Norovirus Virology and Evolution 6

1.1.4 Norovirus Resistance and Immunity 6 Genetic Resistance 7 Acquired Immunity 8 Maternal Immunity 8

1.1.5 Norovirus Vaccines Under Development 9

1.1.6 Use of Infectious Disease Transmission Models in Investigating Vaccination 11

1.1.7 Aim 1 Rational and Overview 13

1.2 Aim 2: SARS-CoV-2 Vaccination and Non-Pharmaceutical Interventions 15

1.2.1 SARS-CoV-2 Burden, Transmission Pathways, and Epidemiological Characteristics 15

1.2.2 SARS-CoV-2 Interventions 17

1.2.3 Modeling of SARS-CoV-2 19

1.2.4 Quantitative Microbial Risk Assessment Models 20

1.2.5 Infectious Disease Transmission Models 21

1.2.6 Integrated Quantitative-Microbial Risk Assessment-Infectious Disease Transmission Model 22

1.2.7 Aim 2 Rational and Overview 23

1.3 Aim 3: Urbanization and Diarrheal Disease Seasonality in Sichuan, China 25

1.3.1 Seasonality of Infectious Disease 26

1.3.2 Changes in the Epidemiological Landscape 26

1.3.3 Burden of Diarrheal Disease in China 27

1.3.4 Diarrheal Diseases Interventions: Water, Sanitation, and Vaccination in China 28

1.3.5 Urbanization in China 30

1.3.6 Urbanization and Meteorological Factors 32

1.3.7 Study Setting: Sichuan Province 33

1.3.8 Shifting Seasonality of All-Cause Diarrhea in Sichuan 35

1.3.9 Aim 3 Rational and Overview 39

2 Manuscript for Aim 1: Pediatric Norovirus Vaccination 42

3 Manuscript for Aim 2: SARS-CoV-2 Vaccination and Non-Pharmaceutical Interventions 97

4 Manuscript for Aim 3: Urbanicity, Urbanization and Diarrheal Disease Seasonality 134

5 Discussion 172

5.1 Overview 172

5.2 Contribution of each specific aim 172

5.2.1 Aim 1: Pediatric norovirus vaccination 172

5.2.2 Aim 2: SARS-CoV-2 vaccination and non-pharmaceutical interventions 175

5.2.3 Aim 3: Urbanicity, urbanization, and diarrheal disease seasonality in Sichuan, China 179

5.3 Data, model choice, and the whirling vortex of analysis 183

5.4 Conclusion 186

6 References 188

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