Citation: Vielot, N.A.; Zepeda, O.; Reyes, Y.; González, F.; Vinjé, J.; Becker-Dreps, S.; Bucardo, F. Household Surveillance for Norovirus Gastroenteritis in a Nicaraguan Birth Cohort: A Nested Case—Control Analysis of Norovirus Risk Factors. Pathogens 2023, 12, 505. https://doi.org/10.3390/ pathogens12030505 Academic Editors: Benjamin Lee, Jessica Crothers and James Church Received: 9 February 2023 Revised: 16 March 2023 Accepted: 20 March 2023 Published: 22 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pathogens Article Household Surveillance for Norovirus Gastroenteritis in a Nicaraguan Birth Cohort: A Nested Case—Control Analysis of Norovirus Risk Factors Nadja Alexandra Vielot 1, * ,† , Omar Zepeda 2,† , Yaoska Reyes 2 , Fredman González 2 , Jan Vinjé 3 , Sylvia Becker-Dreps 1,4,† and Filemón Bucardo 2,† 1 Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; sbd@email.unc.edu 2 Department of Microbiology, National Autonomous University of Nicaragua, Leon 21000, Nicaragua 3 Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA 4 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA * Correspondence: nadjavielot@unc.edu † These authors contributed equally to this work. Abstract: Norovirus causes a large proportion of pediatric acute gastroenteritis (AGE) worldwide, and no vaccines are currently available. To inform public health measures against norovirus gastroenteritis, we assessed risk factors in a case–control study nested in a birth cohort study in Nicaragua. Between June 2017 and January 2022, we followed children weekly for AGE episodes, and collected stool specimens from symptomatic children. Risk factors for AGE were collected during routine weekly visits. Norovirus was detected in stools using real-time reverse transcriptase polymerase chain reaction and positive specimens were genotyped using Sanger sequencing. We included 40 norovirus- positive AGE children matched 1:2 to controls and conducted bivariate and multivariable analyses of norovirus AGE risk factors. Among typeable norovirus infections, GII.4 were more severe than non- GII.4 (four/twenty-one vs. one/nine) and accounted for all emergency visits and hospitalizations. Adjusted conditional logistic regression found that female sex and higher length-for-age Z score were protective against norovirus AGE; a dirt floor in the home, sharing cups or bottles, and recent contact with someone with AGE symptoms were associated with norovirus AGE, though estimates were highly imprecise. Reducing contact with symptomatic persons and with saliva or other bodily fluids on cups or floors could reduce infant norovirus incidence. Keywords: norovirus; acute gastroenteritis; infants; Nicaragua 1. Introduction Globally, norovirus is detected in an estimated 18% of cases of acute gastroenteritis (AGE) [1] and causes approximately 214,000 deaths each year [2]. While norovirus affects all age groups, children and older adults bear the highest burden of disease. In Nicaragua, as in many other settings where rotavirus vaccines have been introduced, norovirus replaced rotavirus as the most common enteric pathogen detected in children with AGE [3,4]. Pediatric norovirus vaccines are currently in development, though efforts are ham- pered by the wide genetic diversity of noroviruses and apparent lack of cross-protection across genotypes [5]. Several vaccine candidates have been evaluated in clinical trials, but absent licensed norovirus vaccines, prevention of norovirus transmission includes common-sense measures, such as hand hygiene, environmental disinfection, and limiting contact with infected persons. As norovirus can be transmitted through contaminated food and water [6,7], improved food safety would also likely decrease norovirus burden. Except for these general measures recommended for the prevention of all fecal–oral pathogens, there is limited scientific evidence on specific modifiable risk factors for norovirus to guide Pathogens 2023, 12, 505. https://doi.org/10.3390/pathogens12030505 https://www.mdpi.com/journal/pathogens