Differences in Rotavirus Shedding by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh 2011-2014 Open Access

Abstract

Background: Oral rotavirus vaccines are less effective in low-income compared to high-income settings. In settings with lower vaccine efficacy, breakthrough rotavirus disease among vaccinated children is common. However, because few studies have examined the impact of rotavirus vaccination on fecal shedding and infectiousness, it is unknown how much these breakthrough cases contribute to transmission.

Methods: We used data from the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) randomized controlled trial to examine the relationship between Rotarix® (RV1) vaccination and quantity of rotavirus shed in stool during episodes of rotavirus gastroenteritis (RVGE). We used multivariable linear regression with robust standard error to analyze 184 episodes of rotavirus diarrhea testing positive by ELISA occurring in children 10 weeks to 1 year of age. The primary outcome of interest was quantity of rotavirus shed in stool by qPCR testing.

Results: Vaccinated children had significantly lower levels of fecal viral shedding compared to unvaccinated children after controlling for age, weight-for-age, height-for-age, exclusive breastfeeding at time of episode, and time in days since symptom onset (mean difference = -0.59 log copies per gram of stool, 95% CI: -0.99, -0.19). We found no evidence of interaction by child age or disease severity (modified Vesikari score). We also found no significant interaction by time when comparing effect estimates between children 10 to 19 weeks of age (after receipt of first dose) to children 19 weeks to one year of age (2 weeks after receipt of second dose).

Conclusions: These results suggest that RV1 vaccination reduces shedding burden among breakthrough cases of RVGE, in addition to preventing RVGE cases entirely. Our results also suggest that breakthrough cases among vaccinated children may have lower transmission potential than cases among unvaccinated children, though further study is needed. 

Table of Contents

Chapter I: Literature Review 1

Introduction 1

Global Burden of Disease 2

Immunity 2

Vaccines 3

Vaccine Impact & Effectiveness 4

Transmission 5

Fecal Shedding 6

Summary 7

Chapter II: Manuscript 9

Introduction 9

Methods 11

Results 13

Discussion 16

Conclusions & Future Research 18

References 19

Tables 25

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Keyword	vaccine effectivness shedding rotavirus
Committee Chair / Thesis Advisor	Lopman, Benjamin, Emory University Rogawski McQuade, Elizabeth, Emory University

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