Mary Allen Staat

The burden of respiratory syncytial virus infection in young children.

BACKGROUND The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. METHODS We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. RESULTS Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. CONCLUSIONS RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection.

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

Respiratory Syncytial Virus–Associated Hospitalizations Among Children Less Than 24 Months of Age

3,918,

Impact of maternal immunization on influenza hospitalizations in infants

435, and

Burden of Human Metapneumovirus Infection in Young Children

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

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

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.).

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

BACKGROUND: Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. However, estimates of the RSV hospitalization burden have varied, and precision has been limited by the use of age strata grouped in blocks of 6 to ≥12 months. METHODS: We analyzed data from a 5-year, prospective, population-based surveillance for young children who were hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain reaction) RSV acute respiratory illness (ARI) during October through March 2000–2005. The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates. RESULTS: There were 559 (26%) RSV-infected children among the 2149 enrolled children hospitalized with ARI (85% of all eligible children with ARI). The average RSV hospitalization rate was 5.2 per 1000 children <24 months old. The highest age-specific rate was in infants 1 month old (25.9 per 1000 children). Infants ≤2 months of age, who comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9 per 1000 children. Most children (79%) were previously healthy. Very preterm infants (<30 weeks’ gestation) accounted for only 3% of RSV cases but had RSV hospitalization rates 3 times that of term infants. CONCLUSIONS: Young infants, especially those who were 1 month old, were at greatest risk of RSV hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy. To substantially reduce the burden of RSV hospitalizations, effective general preventive strategies will be required for all young infants, not just those with risk factors.

Human Rhinovirus Species Associated With Hospitalizations for Acute Respiratory Illness in Young US Children

We sought to determine whether maternal vaccination during pregnancy was associated with a reduced risk of laboratory-confirmed influenza hospitalizations in infants <6 months old. Active population-based, laboratory-confirmed influenza surveillance was conducted in children hospitalized with fever and/or respiratory symptoms in 3 US counties from November through April during the 2002 through 2009 influenza seasons. The exposure, influenza vaccination during pregnancy, and the outcome, positive/negative influenza testing among their hospitalized infants, were compared using logistic regression analyses. Among 1510 hospitalized infants <6 months old, 151 (10%) had laboratory-confirmed influenza and 294 (19%) mothers reported receiving influenza vaccine during pregnancy. Eighteen (12%) mothers of influenza-positive infants and 276 (20%) mothers of influenza-negative infants were vaccinated (unadjusted odds ratio, 0.53; 95% confidence interval, 0.32-0.88 and adjusted odds ratio, 0.52; 95% confidence interval, 0.30-0.91). Infants of vaccinated mothers were 45-48% less likely to have influenza hospitalizations than infants of unvaccinated mothers. Our results support the current influenza vaccination recommendation for pregnant women.

Parainfluenza Virus Infection of Young Children: Estimates of the Population-Based Burden of Hospitalization

BACKGROUND The inpatient and outpatient burden of human metapneumovirus (HMPV) infection among young children has not been well established. METHODS We conducted prospective, population-based surveillance for acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three U.S. counties from 2003 through 2009. Clinical and demographic data were obtained from parents and medical records, HMPV was detected by means of a reverse-transcriptase polymerase-chain-reaction assay, and population-based rates of hospitalization and estimated rates of outpatient visits associated with HMPV infection were determined. RESULTS HMPV was detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Overall annual rates of hospitalization associated with HMPV infection were 1 per 1000 children less than 5 years of age, 3 per 1000 infants less than 6 months of age, and 2 per 1000 children 6 to 11 months of age. Children hospitalized with HMPV infection, as compared with those hospitalized without HMPV infection, were older and more likely to receive a diagnosis of pneumonia or asthma, to require supplemental oxygen, and to have a longer stay in the intensive care unit. The estimated annual burden of outpatient visits associated with HMPV infection was 55 clinic visits and 13 emergency department visits per 1000 children. The majority of HMPV-positive inpatient and outpatient children had no underlying medical conditions, although premature birth and asthma were more frequent among hospitalized children with HMPV infection than among those without HMPV infection. CONCLUSIONS HMPV infection is associated with a substantial burden of hospitalizations and outpatient visits among children throughout the first 5 years of life, especially during the first year. Most children with HMPV infection were previously healthy. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).

Clinical presentations of rotavirus infection among hospitalized children.

BACKGROUND Routine rotavirus vaccination of US infants began in 2006. We conducted active, population-based surveillance for rotavirus gastroenteritis hospitalizations in 3 US counties to assess vaccine impact. METHODS Children <36 months old hospitalized with diarrhea and/or vomiting were enrolled from January through June each year during the period 2006-2009 and tested for rotavirus. Age-stratified rates of hospitalization for rotavirus infection were compared with corresponding vaccination coverage among a control group of children with acute respiratory illness. To assess direct and indirect benefits, vaccination coverage rates in the control group were multiplied by vaccine effectiveness estimates to calculate expected reductions in the rate of hospitalization for rotavirus infection. Rotavirus serotypes were compared across years. RESULTS Compared with 2006, a significant reduction in rates of hospitalization for rotavirus infection (P < .001) was observed in 2008 among all age groups. There was an 87% reduction in the 6-11-month-old age group (coverage, 77%), a 96% reduction in the 12-23-months-old age group (coverage, 46%), and a 92% reduction in the 24-35-month-old age group (coverage, 1%), which exceeded reductions expected on the basis of coverage and vaccine effectiveness estimates. Age-specific rate reductions were nearly equivalent to those expected on the basis of age-specific vaccine coverage in 2009. Predominant strains varied annually: G1P[8] (91%) in 2006; G1P[8] (45%) and G12P[8] (36%) in 2007; G1P[8] (89%) in 2008; and G3P[8] (43%), G2P[4] (34%), and G9P[8] (27%) in 2009. CONCLUSIONS Rotavirus vaccination has dramatically decreased rates of hospitalization for rotavirus infection among children in these US counties. In 2008, reductions were prominent among both vaccine-eligible age groups and older, largely unvaccinated children; the latter likely resulted from indirect protection. Although rates among age groups eligible for vaccination remained low in 2009, indirect benefits disappeared.