GI and GII Norovirus Shedding After Experimental Human Infection Open Access

Shi, Jing (2012)

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GI and GII Norovirus Shedding After Experimental Human Infection

Norovirus (NoV) infection is the main cause of epidemic, acute non-bacterial
gastroenteritis in United States and worldwide. However, little is yet known about the
duration and magnitude of NoV excretion. In addition, the factors that determine NoV
shedding patterns in stools remain unknown. In this study we investigated 51 subjects
who had been experimentally challenged with Norwalk virus (NV) and 15 subjects who
had been challenged with Snow Mountain virus (SMV). Stool specimens were examined
for NoV by quantitative real-time reverse transcription-PCR. We also examined the
relationship between covariates (age, gender, blood type, symptom severity, and pre-
challenge anti-NoV serum IgG) and outcome variables (median viral loads, peak
shedding titer, duration of shedding, cumulative virus shedding, and rate of increase and
decrease in fecal virus titer). A total of 15 (29%) subjects were infected with NV, and
nine (60%) subjects were infected with SMV. Among infected subjects, the median
duration of viral shedding was 20 and 6 days for subjects infected with NV and SMV,
respectively. NV had a similar median peak virus titer compared to SMV (3.03×107
genomic copies/g of stool vs. 1.06×107 genomic copies/g of stool). Peak virus titers were
most commonly found in stools collected after resolution of symptoms. Prolonged
duration of NoV shedding and the high virus titer in stools likely facilitate the
transmission of NoV from infected persons to susceptible hosts through the fecal-oral
route. Additionally, we found that subjects with asymptomatic infections had mean virus
titers in stool similar to those with symptomatic infections, which indicates that
individuals with asymptomatic NoV infections may play a significant role in virus
transmission. No statistically significant correlation was found between any of the
outcome variables and the co-variates. Further studies are needed to identify the factors
that determine the magnitude and duration of NoV shedding.

Table of Contents


Chapter I: Background/Literature Review...1

1. Introduction...2

2. Viral particle structure of NoVs...2

3. Classification...3

4. Transmission...4

5. Clinical features and treatment...5

6. Epidemiology...6

7. Diagnostic and detection methods...7

7.1. Electron Microscopy...7

7.2. Immuno Electron Microscopy...8

7.3. Reverse Transcriptase Polymerase Chain Reaction...8

7.4. Real-time RT-PCR...9

7.5. Enzyme-Linked ImmunoSorbent Assays (ELISA)...10

8. Human Challenge Studies...11

9. Host Susceptibility...12

10. Immunity and Vaccine...13

11. Prevention and Control...15

Chapter II: Manuscript...17

1. Abstract...18

2. Introduction...19

3. Material and methods...22

3.1. Study participants and sample collection...22

3.2. Laboratory Studies...23

3.3. Scoring System for Severity of Gastrointestinal Symptoms...24

3.4. Definitions...25

3.5. Data Collection and Statistical Analysis...25

4. Results...27

5. Discussion...31

6. Tables...36

7. Figures...40

8. References...44

Chapter III: Conclusions/Public Health Implications/Future Directions...52

1. Conclusions...53

2. Public health implications...53

3. Future directions...54

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