Downloaded from http://journals.lww.com/jpgn by BhDMf5ePHKbH4TTImqenVAC0cwDRZApUPs17Rxy9JdyeufP9nt89Oxxw6Uf7NUXB on 12/18/2018 Copyright © ESPGHAN and NASPGHAN. All rights reserved. Genetic Diversity of Norovirus Infections, Coinfections, and Undernutrition in Children From Brazilian Semiarid Region  Rafhaella D.G. Gondim,  Rafaela C. Pankov,  Mara M.G. Prata,  Pedro H.Q.S. Medeiros,  Herlice N. Veras,  Ana K.S. Santos,  Lyvia M.C. Magalha ˜es,  Alexandre Havt, y Tulio M. Fumian, y Marize P. Miagostovich, y Jose ´ P.G. Leite, and  Aldo A.M. Lima ABSTRACT Background and Objective: Norovirus (NoV) infections are known to have high-morbidity and mortality rates and are a major health problem globally. The impact of NoV on child development is, however, poorly understood. We evaluated the distribution of NoV genotypes in children from a low-income Brazilian semiarid region, in relation with their clinical symptoms, nutritional status, and co-pathogens. Methods: The test population included children aged 2 to 36 months from 6 cities of the Brazilian semiarid region. Fecal samples were collected from each child, along with the information regarding their socioeconomic/clinical conditions using a standardized questionnaire. Detection and quantification of NoV were performed by reverse-transcription quantitative polymerase chain reaction, followed by molecular and phylogenetic analyses. Results: The NoV detection rate was 45.2%. Presence of NoV was associated with lower z scores for weight-for-age (P ¼ 0.03), weight-for-height (P ¼ 0.03), and body mass index-for-age (P ¼ 0.03). NoV infection was associated with more frequent respiratory illnesses (P < 0.01). GII.P7 (polymerase) and GII.3 (capsid) were the most frequent NoV genotypes. Analysis of the open reading frame (ORF)1-2 junction identified recombinant NoV strains in 80% of the sequenced samples. Enteroaggregative Escherichia coli coinfection was the major predictor for diarrhea in NoV-positive samples (P < 0.02). Moreover, Shigella spp was also associated with NoV-positive diagnosis (P ¼ 0.02). Conclusions: This study highlights the genetic variability of NoV and, associated co-infections and undernutrition in infants from low-income Brazilian semiarid region. Key Words: diarrhea, northeastern Brazil, pediatrics (JPGN 2018;67: e117–e122) I nfectious diarrhea is the second most common cause of death in children under 5 years of age in developing countries (1). Norovirus (NoV) is estimated to account for approximately 90% of viral outbreaks of gastroenteritis and 50% of outbreaks of gastroenteritis of all causes worldwide (2,3). NoV is a representative genus of the Caliciviridae family. It has a positive single-stranded RNA genome of approximately 7.5 kb, which is organized into 3 open reading frames (ORFs). ORF1 encodes non-structural proteins, while ORF2 and ORF3 encode the major capsid VP1 protein and the minor structural VP2 protein, respectively. Based on the sequence homologies of VP1, NoV strains are classified into 7 genogroups (GI-GVII) and over 40 genotypes. Strains belonging to the GI, GII, and GIV genogroups are known to infect humans (4–6). It is evident that NoV is constantly evolving, through point mutations (antigenic drift) and genetic recombination. High recombination frequencies among different genotypes have been reported in previous studies, most commonly near the ORF1-2 junction. Therefore, it has been recommended that both regions (polymerase and major capsid) need to be genotyped (6,7). Non-severe episodes of diarrhea in the community are of great public health concern, because they are associated with poor What Is Known  Noroviruses are constantly evolving as suggested by their high recombination frequencies among differ- ent genotypes.  Noroviruse infection has been associated with fre- quent diarrhea episodes.  Noroviruse has been consistently associated with the outbreaks of traveler’s diarrhea. What Is New  Noroviruse circulating strains presents high genetic diversity in children from the low-income Brazilian semiarid region.  Noroviruse infection is frequent in subclinical infec- tion in children from Brazil semiarid region.  Noroviruse infections show high rates of entero- pathogen co-infections associated with children from Brazil semiarid region. Received March 2, 2018; accepted June 15, 2018. From the  National Institute of Science and Technology & Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara ´, Fortaleza, and the y Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Address correspondence and reprint requests to Rafhaella D.G. Gondim, MD, R. Cel. Nunes de Melo, 1315, Rodolfo Teo ´filo, Fortaleza, CEP 60.430-270, CE, Brazil, Institute of Biomedicine, Faculty of Medicine, Federal University of Ceara ´, Fortaleza, CE, Brazil (e-mail: rafha_ndg@hotmail.com). Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jpgn.org). This work was supported by the National Fund for Scientific and Technologi- cal Development (FNDCT; Finep no. 0460.08), the Excellence Program of Research (PROEP-CNPq/IOC), and the General Coordination of Labora- tories/Secretary of Health Surveillance, Ministry of Health. The authors report no conflicts of interest. Copyright # 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000002085 ORIGINAL ARTICLE:GASTROENTEROLOGY JPGN  Volume 67, Number 6, December 2018 e117