Acquired immunity to enteric viruses in an Indian birth cohort Open Access

Kates, Israel (Spring 2021)

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Diarrheal disease causes widespread morbidity and mortality among children under 5 globally; enteric viruses contribute to this burden. Acquired immunity due to initial infection has been shown to protect against re-infection by some enteric viruses, but the extent and duration of such immunity remains to be fully explored. We obtained a dataset of 373 children and 1,831 diarrheal episodes from an Indian birth cohort and examined natural immunity for astrovirus, sapovirus, norovirus GI and norovirus GII. We fit a Cox Proportional Hazards Model and obtained hazard ratios for virus-specific diarrheal episodes, comparing time to episode among children who had already experienced one virus-specific episode and those who had not yet experienced one. We also analyzed protection against overall diarrheal episodes (not virus-specific) as well as cross-protection between viruses, and lastly fit a frailty model to adjust our results for differential baseline risk. We found that a prior episode did not confer substantial protection against subsequent episodes associated with the same virus. Compared to those without a previous episode of astrovirus, children who had already experienced one had a slightly lower hazard of subsequent episodes of astrovirus (HR=0.83, 95% CI: 0.55, 1.25). Children who had already experienced an episode of norovirus GI had a 65% higher hazard of subsequent episodes involving norovirus GI (HR=1.65, 95% CI: 0.64, 4.25), although this effect was mitigated in the frailty analysis (HR=1.28, 95% CI: 0.53, 3.07). Sapovirus (HR=1.03, 95% CI: 0.77, 1.38) and norovirus GII (HR=1.08, 95% CI: 0.79, 1.48) did not show substantial protection. Children who experienced one diarrheal episode (regardless of pathogen presence) had a 30% higher hazard of subsequent episodes (HR=1.30, 95% CI: 1.10, 1.52); however, this was reduced in the frailty analysis (HR=0.86, 95% CI: 0.73, 1.02). Limited evidence of immunity may result from our episode-centered study design and small sample size. Results indicate host-specific factors that impact an individual’s risk may affect acquisition of natural immunity. Further research, including longitudinal seroprevalence and multi-site cohort studies, is needed to disentangle the extent and duration of acquired immunity to enteric viruses.

Table of Contents

Chapter 1: Literature Review

Chapter 2: Manuscript

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