Marika K. Iwane

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.

BACKGROUND: The disease burden of influenza infection among children is not well established. We conducted a population-based surveillance of medical visits associated with laboratory-confirmed influenza. METHODS: Eligible children were younger than five years of age, resided in three U.S. counties, and had a medical visit for an acute respiratory tract infection or fever. Nasal and throat swabs were tested for the influenza virus by viral culture and polymerase-chain-reaction assay. Epidemiologic data were collected from parental surveys and chart reviews. Children who were hospitalized were enrolled prospectively from 2000 through 2004. Population-based rates of hospitalizations associated with influenza were calculated. Children who were seen in selected pediatric clinics and emergency departments during two influenza seasons (2002-2003 and 2003-2004) were systematically enrolled. The rates of visits to clinics and emergency departments associated with influenza were estimated. RESULTS: The average annual rate of hospitalization associated with influenza was 0.9 per 1000 children. The estimated burden of outpatient visits associated with influenza was 50 clinic visits and 6 emergency department visits per 1000 children during the 2002-2003 season and 95 clinic visits and 27 emergency department visits per 1000 children during the 2003-2004 season. Few children who had laboratory-confirmed influenza were given a diagnosis of influenza by the treating physician in the inpatient (28 percent) or outpatient (17 percent) settings. CONCLUSIONS: Among young children, outpatient visits associated with influenza were 10 to 250 times as common as hospitalizations. Few influenza infections were recognized clinically.

BACKGROUND: Upper respiratory tract illnesses have been associated with an increased risk of ischemic heart disease and stroke. During two influenza seasons, we assessed the influence of vaccination against influenza on the risk of hospitalization for heart disease and stroke, hospitalization for pneumonia and influenza, and death from all causes. METHODS: Cohorts of community-dwelling members of three large managed-care organizations who were at least 65 years old were studied during the 1998-1999 and 1999-2000 influenza seasons. Administrative and clinical data were used to evaluate outcomes, with multivariable logistic regression to control for base-line demographic and health characteristics of the subjects. RESULTS: There were 140,055 subjects in the 1998-1999 cohort and 146,328 in the 1999-2000 cohort, of which 55.5 percent and 59.7 percent, respectively, were immunized. At base line, vaccinated subjects were on average sicker, having higher rates of most coexisting conditions, outpatient care, and prior hospitalization for pneumonia than unvaccinated subjects. Unvaccinated subjects, however, were more likely to have been given a prior diagnosis of dementia or stroke. Vaccination against influenza was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19 percent during both seasons [P<0.001]), cerebrovascular disease (reduction of 16 percent during the 1998-1999 season [P<0.018] and 23 percent during the 1999-2000 season [P<0.001]), and pneumonia or influenza (reduction of 32 percent during the 1998-1999 season [P<0.001] and 29 percent during the 1999-2000 season [P<0.001]) and a reduction in the risk of death from all causes (reduction of 48 percent during the 1998-1999 season [P<0.001] and 50 percent during the 1999-2000 season [P<0.001]). In analyses according to age, the presence or absence of major medical conditions at base line, and study site, the findings were consistent across all subgroups. CONCLUSIONS: In the elderly, vaccination against influenza is associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza as well as the risk of death from all causes during influenza seasons. These findings highlight the benefits of vaccination and support efforts to increase the rates of vaccination among the elderly.

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.

OBJECTIVE: Respiratory syncytial virus (RSV), influenza virus, and parainfluenza viruses (PIV) cause significant morbidity in young children. Although only influenza virus infection and illness is currently vaccine-preventable, vaccines are under development for RSV and PIV. We established a prospective, active population-based surveillance network to provide precise estimates of hospitalization rates for viral acute respiratory illness (ARI) in young children and to measure the potential impact of enhanced vaccine usage on these rates. METHODS: Prospective, active population-based surveillance was conducted in young children who were hospitalized for ARI from October 1, 2000, to September 30, 2001, in Monroe County, New York (Rochester area) and Davidson County, Tennessee (Nashville area). Eligible children younger than 5 years were those who resided in surveillance counties and were hospitalized for febrile or acute respiratory illness. Viral culture and polymerase chain reaction identified viruses from nasal and throat samples obtained from all surveillance children. We measured population-based rates of hospitalization for RSV, influenza virus, and PIV as well as demographic, clinical, and risk factor assessment for each virus. RESULTS: Of 812 eligible hospital admissions, 592 (73%) children were enrolled. Of the enrolled children, RSV was identified in 20%, influenza in 3%, PIV in 7%, other respiratory viruses in 36%, and no detectable virus in 39%. Population-based rates of ARI hospitalizations in children younger than 5 years were 18 per 1000. Virus-positive hospitalization rates per 1000 children were 3.5 for RSV, 1.2 for PIV, and 0.6 for influenza virus. Younger age (particularly <1 year), black and Hispanic race/ethnicity, male gender, and presence of chronic underlying illness were associated with higher hospitalization rates. CONCLUSIONS: This study confirms that children younger than 5 years and particularly children younger than 1 year have a high burden of hospitalization from RSV, influenza, and PIV. The enhanced use of influenza vaccine and the development of RSV and PIV vaccines have the potential to reduce markedly the pediatric morbidity from ARIs.