Aaron T. Curns

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

The Roles of Clostridium difficile and Norovirus Among Gastroenteritis-Associated Deaths in the United States, 1999–2007

3,918,

Reduction in Acute Gastroenteritis Hospitalizations among US Children After Introduction of Rotavirus Vaccine: Analysis of Hospital Discharge Data from 18 US States

435, and

Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006.

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

Infant Rotavirus Vaccination May Provide Indirect Protection to Older Children and Adults in the United States

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.).

Direct and Indirect Effects of Rotavirus Vaccination Upon Childhood Hospitalizations in 3 US Counties, 2006–2009

BACKGROUND Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus. METHODS Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths. RESULTS Gastroenteritis mortality averaged 39/1000000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥ 65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains. CONCLUSIONS Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.

Risk factors for bronchiolitis-associated deaths among infants in the United States

BACKGROUND In 2006, RotaTeq (RV5) was recommended for routine vaccination of United States (US) infants. We compared hospitalization rates for acute gastroenteritis among US children aged <5 years during pre-RV5 rotavirus seasons from 2000 through 2006 with those during the post-RV5 2007 and 2008 seasons. METHODS Using 100% hospital discharge data from 18 states, accounting for 49% of the US population, we calculated acute gastroenteritis hospitalization rates for children aged <5 years by rotavirus season, 8 age groups (0-2, 3-5, 6-11, 12-17, 18-23, 24-35, 36-47, and 48-59 months), and state. RESULTS Compared with the median rate for the 2000-2006 rotavirus seasons (101.1 hospitalizations per 10,000 children), the rates for 2007 and 2008 (85.5 and 55.5 hospitalizations per 10,000 children) were 16% and 45% lower, respectively. Children aged 0-2 months had a 28% reduction, those aged 6-23 months had a reduction of 50%, and children aged 3-5 months and 24-59 months had reductions ranging between 42% and 45% during the 2008 rotavirus season, compared with the median rate for 2000-2006 rotavirus seasons. CONCLUSIONS The introduction of the RV5 vaccine was associated with a dramatic reduction in hospitalizations for acute gastroenteritis among US children during the 2008 rotavirus season.

Active, Population-Based Surveillance for Severe Rotavirus Gastroenteritis in Children in the United States

Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in the United States during 1980 through 1996. In this study, we updated national estimates of RSV hospitalization rates among US children through 2006. Methods: We conducted a retrospective analysis of hospital discharges for lower respiratory tract illness (LRTI) in children <5 years old from the National Hospital Discharge Survey. LRTI hospitalizations were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RSV-coded hospitalizations were International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11, 480.1, and 079.6. RSV-associated hospitalizations were the sum of RSV-coded hospitalizations and a proportion of hospitalizations coded as bronchiolitis and pneumonia during the RSV season. Results: RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million LRTI hospitalizations among children <5 years of age during the 10 study years, 1997–2006. The RSV-coded hospitalization rate in infants <1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants <3 months old (48.9 per 1000), followed by infants 3 to 5 months old (28.4 per 1000), and lower among those >1 year old (1.8 per 1000). An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in children <5 years of age. Conclusion: RSV hospitalization rates remained steady during 1997 to 2006 and were a substantial burden in the United States, especially among infants and young children. A safe and effective RSV vaccine is needed.

Increasing Rates of Gastroenteritis Hospital Discharges in US Adults and the Contribution of Norovirus, 1996–2007

Following the introduction of rotavirus vaccination in the United States, rotavirus and cause-unspecified gastroenteritis discharges significantly decreased in 2008 in the 0-4, 5-14, and 15-24-year age groups, with significant reductions observed in March, the historic peak rotavirus month, in all age groups. We estimate that 15% of the total 66 000 averted hospitalizations and 20% of the

Rotavirus Vaccine and Health Care Utilization for Diarrhea in U.S. Children

204 million in averted direct medical costs attributable to the vaccination program were among unvaccinated 5-24 year-olds. This study demonstrates a previously unrecognized burden of severe rotavirus in the population >5 years and the primacy of very young children in the transmission of rotavirus.