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For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix® vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2–11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.

Background Acute gastroenteritis (AGE) is a major cause of morbidity in children. Viral pathogens are the most common infectious agents. Differences in illness characteristics of AGE with and without virus detection are poorly defined. We compared AGE illness characteristics between children with and without any-virus detected, and with single vs. multiple viruses detected. Methods Children between 15 days and 17 years with AGE defined as diarrhea (>3 loose stools/24 hours) or any vomiting within 10 days duration were enrolled in Vanderbilt Children’s Hospital inpatient, ED, and outpatient settings from December 2012 to November 2015. Stool specimens were tested by RT-qPCR for norovirus, sapovirus, and astrovirus and by ELISA (VP6 antigen [Rotaclone®]) for rotavirus. Results Of 3,705 children enrolled, 2,892 (78%) specimens were collected. A single virus was detected in 1,109 (38%) stools [51% norovirus, 20% rotavirus, 21% sapovirus, and 8% astrovirus], viral co-detections were found in 115 (4%) stools, and 1,665 (58%) had no detected viruses. Table 1 compares children with and without any-virus detected. Children with a single-virus detected were older than those with >1 virus detected (1.8 vs. 1.5 years [P < 0.05]) with no other significant differences. Conclusion Children with any-virus detected had more severe symptoms, higher MVS, and more frequently reported sick contacts compared with no-virus detected. Children with no-virus detected were more likely to present with fever and higher temperatures, which may be due to bacterial organisms. These data highlight the importance of infection-prevention precautions in the community and the need for additional testing to define the etiologic spectrum of AGE in children. Disclosures N. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.

Background International Classification of Diseases (ICD) diagnostic codes from acute gastroenteritis (AGE)-associated medical encounters are used for AGE disease burden estimates, yet the validity of AGE-related ICD codes in both pediatric and adult populations is unknown. We estimated the validity of AGE-related diagnostic codes in these populations using two different multi-regional AGE active surveillance platforms. Methods Diagnostic codes, demographic and clinical characteristics, and stool pathogen results from AGE-associated medical encounters were obtained for enrolled children

We report an increase in the proportion of genotype GI.6 norovirus outbreaks in the United States from 1.4% in 2010 to 7.7% in 2012 (p

Background Acute gastroenteritis (AGE) is a frequent sequela in children undergoing hematopoietic cell transplant (HCT). Although rotavirus and norovirus have been implicated as important causes of AGE, the frequency of other pathogens is unknown. Little data exist on longitudinal prevalence of infectious AGE in HCT. Methods From February 2015 to May 2016, subjects Results Thirty-one patients were enrolled at four sites (Seattle: 13, Kansas City: 8, Oakland: 6, Nashville: (4) with median age 5 (IQR 3–10) years. Two hundred sixteen samples were obtained with median 7 samples/subject. During the first 100 days, 29 (94%) subjects met the AGE definition. Thirty-six single pathogen detections occurred in 16 (52%) subjects. Clostridium difficile was the most frequent pathogen (Figure 1), with 14 detections in nine patients, all ≥3 years; 50% of detections were asymptomatic. Seven (50%) detections occurred at HCT onset and none received targeted C. difficile therapy. Sapovirus was detected nine times in four patients, with seven (78%) detections associated with AGE symptoms. Rotavirus was detected nine times, during five symptomatic episodes, in three patients. Adenovirus was detected four times in three patients and all were symptomatic. Conclusion We longitudinally characterized the etiology of infectious AGE in children undergoing HCT. Despite the majority of patients meeting the definition for AGE, only half had a pathogen detected, suggesting that differentiating infectious vs. noninfectious AGE (e.g., medication induced) in this population is difficult. Although all subjects with adenovirus and most with sapovirus were symptomatic, asymptomatic C. difficile detection was common. Interestingly, norovirus was not detected. Further investigation of AGE is warranted in this population. Disclosures All authors: No reported disclosures.

Background Norovirus is a leading cause of acute gastroenteritis (AGE) in all age groups. Although at least 28 different genotypes infecting humans have been reported, most outbreaks over the last 15 years have been caused by genogroup II (GII) viruses, of which GII.4 viruses have caused more than 50%. Since clinical differences between different genotypes are poorly understood, we sought to compare clinical characteristics in children infected with GII.4 and non-GII.4 viruses. Methods Children between 15 days and 17 years who presented with AGE defined as diarrhea (≥3 loose stools in a 24 hour period) or vomiting (≥1 episodes in a 24 hour period) within 10 days duration were recruited in outpatient, emergency, and inpatient settings in Nashville, TN, during 2012–2015. Stool specimens were tested by RT-qPCR for GI and GII norovirus. Norovirus-positive specimens were genotyped by sequencing of a partial region of the capsid gene. In this study, we excluded children infected with GI, mixed GI/GII and non-typeable GII viruses. Results Of 3,705 AGE subjects enrolled, 2,892 (78%) specimens were collected, 637 (22%) tested norovirus-positive (567 [89%] GII, 62 [10%] GI, and 8 [1%] mixed GI/GII). Of the 567 GII viruses, 461 (81%) were able to be genotyped and of those 238/461 (51.6%) were typed as GII.4 and 223/461 (48.3%) were typed as other GII genotypes (non-GII.4, primarily GII.3 [65/ 461, 14.1%], GII.6 [48/461, 10.4%] and GII.7 [36/461, 7.8%]). Over three AGE seasons, GII.4 represented 64/117 (54%), 79/178 (44%), and 71/166 (57%), of the GII infections, respectively. Compared with non-GII.4 subjects, GII.4 subjects were more likely to be younger (15.5 vs. 21.3 months, P < 0.01), and less likely to attend daycare (23% vs. 39%, P < 0.01). GII.4 subjects also were more likely to present with diarrhea (75% vs. 57%, P < 0.01) and had higher median modified Vesikari score (7 vs. 6, P < 0.01). Conclusion Children infected with GII.4 viruses were younger, less likely to attend child care, more likely to present with diarrhea, and had a more severe illness compared with those with non-GII.4 infections. These data provide important information on the genotype distribution of norovirus in children with AGE in Tennessee and highlight GII.4 as the most prevalent strain. Disclosures N. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.

Group A Rotaviruses (RVA) are double stranded RNA viruses that are a significant cause of acute pediatric gastroenteritis. Beginning in 2006 and 2008, respectively, two vaccines, Rotarix™ and RotaTeq®, have been approved for use in the USA for prevention of RVA disease. The effects of possible vaccine pressure on currently circulating strains in the USA and their genome constellations are still under investigation. In this study we report 33 complete RVA genomes (ORF regions) collected in multiple cities across USA during 2006 – 2009, including 8 collected from children with verified receipt of 3 doses of rotavirus vaccine. The strains included 16 G1P[8], 10 G3P[8], and 7 G9P[8]. All 33 strains had a Wa like backbone with the consensus genotype constellation of G(1/3/9)-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. From maximum likelihood based phylogenetic analyses, we identified 3 to7 allelic constellations grouped mostly by respective G types, suggesting a possible allelic segregation based on the VP7 gene of RVA primarily for the G3 and G9 strains. The vaccine failure strains showed similar grouping for all genes in G9 strains and most genes of G3 strains suggesting that these constellations were necessary to evade vaccine-derived immune protection. Substitutions in the antigenic region of VP7 and VP4 genes were also observed for the vaccine failure strains which could possibly explain how these strains escape vaccine induced immune response. This study helps elucidate how RVA strains are currently evolving in the population post vaccine introduction and supports the need for continued RVA surveillance.

BACKGROUND Parainfluenza virus (PIV) is the second leading cause of hospitalization for respiratory illness in young children in the United States. Infection can result in a full range of respiratory illness, including bronchiolitis, croup, and pneumonia. The recognized human subtypes of PIV are numbered 1-4. This study calculates estimates of PIV-associated hospitalizations among U.S. children younger than 5 years using the latest available data. METHODS Data from the National Respiratory and Enteric Virus Surveillance System were used to characterize seasonal PIV trends from July 2004 through June 2010. To estimate the number of PIV-associated hospitalizations that occurred annually among U.S. children aged

To the Editor: Group A rotaviruses (RVAs) are a leading cause of acute gastroenteritis-associated deaths among children

Cases of rotavirus-associated acute gastroenteritis have declined since the introduction of rotavirus vaccines, but the burden of norovirus-associated acute gastroenteritis in children remains to be assessed.We conducted active surveillance for laboratory-confirmed cases of norovirus among children younger than 5 years of age with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings. The children resided in one of three U.S. counties during the years 2009 and 2010. Fecal specimens were tested for norovirus and rotavirus. We calculated population-based rates of norovirus-associated acute gastroenteritis and reviewed billing records to determine medical costs; these data were extrapolated to the U.S. population of children younger than 5 years of age.Norovirus was detected in 21% of young children (278 of 1295) seeking medical attention for acute gastroenteritis in 2009 and 2010, with norovirus detected in 22% (165 of 742) in 2009 and 20% (113 of 553) in 2010 (P=0.43). The virus was also detected in 4% of healthy controls (19 of 493) in 2009. Rotavirus was identified in 12% of children with acute gastroenteritis (152 of 1295) in 2009 and 2010. The respective rates of hospitalization, emergency department visits, and outpatient visits for the norovirus were 8.6, 146.7, and 367.7 per 10,000 children younger than 5 years of age in 2009 and 5.8, 134.3, and 260.1 per 10,000 in 2010, with an estimated cost per episode of $3,918, $435, and $151, respectively, in 2009. Nationally, we estimate that the average numbers of annual hospitalizations, emergency department visits, and outpatient visits due to norovirus infection in 2009 and 2010 among U.S. children in this age group exceeded 14,000, 281,000, and 627,000, respectively, with more than $273 million in treatment costs each year.Since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute gastroenteritis in U.S. children and is associated with nearly 1 million health care visits annually. (Funded by the Centers for Disease Control and Prevention.).

We report molecular evidence for the presence of spotted fever group rickettsiae (SFGR) in ticks collected from roe deer, addax, red foxes, and wild boars in Israel. Rickettsia aeschlimannii was detected in Hyalomma marginatum and Hyalomma detritum while Rickettsia massiliae was present in Rhipicephalus turanicus ticks. Furthermore, a novel uncultured SFGR was detected in Haemaphysalis adleri and Haemaphysalis parva ticks from golden jackals. The pathogenicity of the novel SFGR for humans is unknown; however, the presence of multiple SFGR agents should be considered when serological surveillance data from Israel are interpreted because of significant antigenic cross-reactivity among Rickettsia. The epidemiology and ecology of SFGR in Israel appear to be more complicated than was previously believed. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.