Norovirus and medically attended gastroenteritis in U.S. children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established. METHODS: From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged <5 years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing. RESULTS: Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P < .001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P < .001). CONCLUSIONS: FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.

Genotypic and epidemiologic trends of norovirus outbreaks in the United States, 2009 to 2013.

Noroviruses are the leading cause of epidemic acute gastroenteritis in the United States. From September 2009 through August 2013, 3,960 norovirus outbreaks were reported to CaliciNet. Of the 2,895 outbreaks with a known transmission route, person-to-person and food-borne transmissions were reported for 2,425 (83.7%) and 465 (16.1%) of the outbreaks, respectively. A total of 2,475 outbreaks (62.5%) occurred in long-term care facilities (LTCF), 389 (9.8%) in restaurants, and 227 (5.7%) in schools. A total of 435 outbreaks (11%) were typed as genogroup I (GI) and 3,525 (89%) as GII noroviruses. GII.4 viruses caused 2,853 (72%) of all outbreaks, of which 94% typed as either GII.4 New Orleans or GII.4 Sydney. In addition, three non-GII.4 viruses, i.e., GII.12, GII.1, and GI.6, caused 528 (13%) of all outbreaks. Several non-GII.4 genotypes (GI.3, GI.6, GI.7, GII.3, GII.6, and GII.12) were significantly more associated with food-borne transmission (odds ratio, 1.9 to 7.1; P < 0.05). Patients in LTCF and people ≥65 years of age were at higher risk for GII.4 infections than those in other settings and with other genotypes (P < 0.05). Phylogeographic analysis identified three major dispersions from two geographic locations that were responsible for the GI.6 outbreaks from 2011 to 2013. In conclusion, our data demonstrate the cyclic emergence of new (non-GII.4) norovirus strains, and several genotypes are more often associated with food-borne outbreaks. These surveillance data can be used to improve viral food-borne surveillance and to help guide studies to develop and evaluate targeted prevention methods such as norovirus vaccines, antivirals, and environmental decontamination methods.

Etiology of viral gastroenteritis in children <5 years of age in the United States, 2008-2009.

BACKGROUND: Although rotavirus and norovirus cause nearly 40% of severe endemic acute gastroenteritis (AGE) in children <5 years of age in the United States, there are limited data on the etiologic role of other enteric viruses in this age group. METHODS: We conducted active population-based surveillance in children presenting with AGE to hospitals, emergency departments, and primary care clinics in 3 US counties. Stool specimens from these children and from age-matched healthy controls collected between October 2008 and September 2009 were tested for enteric adenovirus, astrovirus, sapovirus, parechovirus, bocavirus, and aichivirus. Typing was performed by sequencing and phylogenetic analysis. RESULTS: Adenovirus, astrovirus, sapovirus, parechovirus, bocavirus, and aichivirus were detected in the stool specimens of 11.8%, 4.9%, 5.4%, 4.8%, 1.4%, and 0.2% of patients with AGE and 1.8%, 3.0%, 4.2%, 4.4%, 2.4%, and 0% of healthy controls, respectively. Adenovirus (type 41), astrovirus (types 1, 2, 3, 4, and 8), sapovirus (genogroups I and II), parechovirus (types 1, 3, 4, and 5), and bocavirus (types 1, 2, and 3) were found cocirculating. CONCLUSIONS: Adenovirus, astrovirus, and sapovirus infections were detected in 22.1% of the specimens from children <5 years of age who had medical visits for AGE and tested negative for rotavirus and norovirus. No causal role for parechovirus and bocavirus was found.

Incidence of Medically-Attended Norovirus-Associated Acute Gastroenteritis in Four Veteran's Affairs Medical Center Populations in the United States, 2011-2012.

An estimated 179 million acute gastroenteritis (AGE) illnesses occur annually in the United States. The role of noroviruses in hospital-related AGE has not been well-documented in the U. S. We estimated the population incidence of community- acquired outpatient and inpatient norovirus AGE encounters, as well as hospital-acquired inpatient norovirus AGE among inpatients at four Veterans Affairs (VA) Medical Centers (VAMCs). Fifty (4%) of 1,160 stool specimens collected ≤7 days from symptom onset tested positive for norovirus. During a one year period, the estimated incidence of outpatient, community- and hospital-acquired inpatient norovirus AGE was 188 cases, 11 cases, and 54 cases/ 100,000 patients, respectively. This study demonstrates the incidence of outpatient and community- and hospital-acquired inpatient norovirus AGE among the VA population seeking care at these four VAMCs.