Comparison of infection and illness between two Norwalk virus inocula (8FIIa and 8FIIb) translation missing: es.hyrax.visibility.files_restricted.text

Rahman, Mumu (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/np193b18d?locale=es
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Abstract

Noroviruses (NoVs) are a leading cause of epidemic gastroenteritis. Human challenge studies have been used to examine the infectivity, pathogenicity, and host immune response to NoV. Several human challenge studies have been performed using Norwalk virus (a prototype Genogroup I NoV) inocula purified from the stools of infected individuals. Surprisingly little is known about differences in infection and illness in human volunteers challenged with different preparations of Norwalk virus (NV) inocula. The goal of this study was to compare the response among study subjects who received a secondary NV inoculum (8FIIb), compared to subjects who received its precursor, the 8FIIa. We investigated a total of 160 subjects: 76 subjects were experimentally challenged with NV inoculum 8FIIa, and 84 subjects were challenged with 8FIIb. We compared the difference in infection, illness, mean severity score, blood types, and duration of viral shedding between two groups of subjects. We also examined the demographic characteristics and secretor status of 8FIIa- and 8FIIb-inoculated subjects. There were no statistically significant differences in overall infection and illness rates between subjects inoculated with 8FIIa and 8FIIb. However, subjects challenged with 8FIIA dose above the ID50 had significantly more illness (94.1%) compared to subjects who were challenged with high doses of 8FIIb (47.1%), P=0.0. Comparison of mean severity score between the two groups of inoculated subjects did not show any significant difference. We observed that infection with 8FIIb was significantly associated with longer duration of viral shedding (P=0.02), and there was a significant difference in duration of viral shedding by dose for both inocula (P=0.00). The results from this study contribute to our understanding and knowledge about NoV infections, pathogenesis, and viral shedding. This information can guide future NoV human challenge studies to test candidate NoV vaccines and treatment efficacy.

Table of Contents

Chapter I: Background/Literature Review………………………………………………2

1. Introduction………………………………………………………………………………..3

2. Structure of NoVs and Classification……………………………………………......4

3. Modes of Transmission and Risk factors…………………………………………..6

4. Clinical features of Norovirus infection and treatment……………………… 7

5. Pathogenesis and host susceptibility………………………………………………. 10

6. Immunity and vaccine……………………………………………………………………12

7. 8FIIa and 8FIIb inoculum………………………………………………………………14

8. Human Challenge studies……………………………………………………………….15

9. Diagnostic and detection methods……………………………………………………17

10. Prevention and control………………………………………………………………….19

Chapter II: Manuscript………………………………………………………22

1. Abstract…………………………………………………………………………………………23

2. Introduction………………………………………………………………………………….24

3. Material and methods…………………………………………………………………….26

4. Laboratory Tests …………………………………………………………………….29

5. Definitions……………………………………………………………………………………30

6. Statistical Analysis…………………………………………………………………………31

7. Results…………………………………………………………………………….……………32

8. Discussion………………………………………………………………………….…………37

9. Tables………………………………………………………………………………………….40

10. References …………………………………………………………………………………49

Chapter III: Conclusions/Public Health Implications/Future Directions

1. Conclusions……………………………………………………………………………………63

2. Public health implications………………………………………………………………63

3. Future directions……………………………………………………………………………63

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