The Etiological Roles of Astrovirus, Sapovirus, and Norovirus as a Cause of Diarrheal Episodes in a Birth Cohort of Indian Children: 2002 – 2006 Public

Abstract

BACKGROUND

Diarrheal diseases are a leading cause of global under-five mortality with nearly 500,000 deaths each year, nearly one-quarter of which occur in India. Following introduction of routine rotavirus vaccination in India in 2016, diarrheal etiology is likely to change. We studied the roles of astrovirus, sapovirus, and norovirus genotypes 1 and 2 as etiologic drivers of diarrhea in a birth cohort in South India prior to rotavirus vaccine introduction.

METHODS

We reanalyzed diarrheal and routine surveillance stool samples from a birth cohort study of children in Vellore, India between 2002 and 2003. Samples were tested for presence of astrovirus, sapovirus, and norovirus genotypes 1 and 2 using real time reverse transcriptase-polymerase chain reaction. We calculated unadjusted and age-adjusted pathogen-specific odds ratios (ORs) for diarrhea using logistic regression modeling.

RESULTS

We analyzed 1,122 diarrheal and 1,085 routine surveillance stool samples from 337 children. Overall, pathogen presence decreased with age in both diarrheal and routine samples. Norovirus genotype 2 was the most prevalent pathogen found among both diarrheal (14%) and routine samples (14%). Presence of sapovirus was higher among diarrheal (13%) versus routine samples (8%). Astrovirus was present in 7% of diarrheal and 3% of routine samples. After adjusting for age, only sapovirus was associated with increased odds of diarrhea (OR = 1.57, 95% confidence interval (CI): 1.19, 2.08). Though the null was within the 95% CI, astrovirus was associated with increased odds of diarrhea, when adjusted for age and sex (OR = 1.50, 95% CI: 0.88, 2.57). Increased odds of diarrhea were not seen in the adjusted models for norovirus genotype 1 (OR = 0.81, 95% CI: 0.54, 1.22) or norovirus genotype 2 (OR = 0.95, 95% CI: 0.74, 1.22), which may be accounted for by common norovirus reinfection and partial conferred immunity.

DISCUSSION

Sapovirus is important in diarrheal etiology among children under 12 months of age in South India. The presence of astrovirus and norovirus were not significant drivers of diarrheal episodes. Our findings suggest that interventions targeted at sapovirus infections in 0 to 12-month-old children have the potential to greatly reduce childhood diarrheal disease morbidity in South India.

Table of Contents

Introduction 1

Methods 4

Study Design, Participant Enrollment, and Follow-Up 4

Diarrheal Disease Surveillance 5

Statistical Analysis 6

Results 6

Baseline Characteristics 6

Viral Pathogen Detection 7

Regression Results 8

Astrovirus 8

Sapovirus 9

Norovirus 9

Discussion 9

References 14

Tables 17

Table 1. 17

Table 2. 18

Table 3. 19

Table 4. 20

Figures 21

Figure 1. 21

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Mot-clé	diarrheal etiology astrovirus diarrhea norovirus sapovirus
Committee Chair / Thesis Advisor	Benjamin Lopman, Emory University
Committee Members	Julia Baker, Emory University

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