Population-Based Surveillance for Hospitalizations Associated With Respiratory Syncytial Virus, Influenza Virus, and Parainfluenza Viruses Among Young Children

Study Design

Population-based rates of hospitalizations associated with laboratory-confirmed acute respiratory viral illness in children who were younger than 5 years and residing in Monroe County, New York, and Davidson County, Tennessee, were determined. Influenza virus, RSV, and PIV were the focus of this report given their known contribution to serious respiratory illness in children and because of the NVSN focus on infections for which vaccines are available or under development. The study of human metapneumovirus has been presented elsewhere.^13,14 Surveillance was conducted from October 1, 2000, through September 30, 2001, in 2 hospitals in Monroe County and 3 hospitals in Davidson County, which admitted >95% of the hospitalized children who reside in those counties (see below). The hospitals are located in the cities of Rochester, New York, and Nashville, Tennessee, which are the urban centers of the counties. Children in the surrounding suburban and rural areas in each county are also admitted to these hospitals; children from outlying counties were excluded because a greater proportion were hospitalized elsewhere. Institutional Review Boards of the 2 study sites, the participating surveillance hospitals, and the CDC approved the study.

Study nurses identified children who were hospitalized between 7 am on Sunday and 7 am on Thursday at each surveillance hospital each week. Children were considered for enrollment when they were younger than 5 years, resided in Monroe or Davidson counties, were admitted within 48 hours of an enrollment period, and had an admitting diagnosis (as reported by the admitting physician) suggestive of an ARI or ARI-related condition (acute respiratory illness, apnea, asthma, bronchiolitis, croup, cystic fibrosis exacerbation, febrile neonate, febrile seizure, fever without localizing signs, hypothermia, influenza, otitis media, other respiratory infection, paroxysmal cough, pharyngitis, pneumonia, respiratory distress, RSV, rule-out sepsis, sinusitis, group A β-hemolytic streptococcal pharyngitis, tonsillitis, upper respiratory illness, wheezing). Furthermore, children were excluded when they had a known nonrespiratory cause for hospitalization, had respiratory symptom duration >14 days, were transferred from another surveillance hospital where they would have been already enrolled, were discharged from a hospital in the previous 4 days, or were newborns who had never left the hospital. When eligibility was unclear to study nurses, they referred the case to a study investigator, who made the final determination on the basis of information available at admission. Informed written consent was obtained from each child’s parent or guardian before enrollment.

Nasal and throat swabs were obtained from each enrolled child, combined into a tube of veal-infusion broth transport medium, and delivered at ambient temperature within 1 to 2 hours to the research virology laboratory at each site. Viral cultures were processed immediately. For reverse transcription-PCR (RT-PCR) testing, sample aliquots were collected in lysis buffer and frozen at −70°C until shipped in batches to the CDC for RNA extraction and RT-PCR. The details of the laboratory methods have been described previously.^11,12 RSV, influenza virus types A and B, and PIV types 1 to 3 were the primary virus types targeted for detection by tissue culture methods at research laboratories in Rochester and Nashville. Aliquots of each specimen were inoculated onto conventional viral cell cultures using primary rhesus monkey kidney, HEp-2, and NCI-H292 cells and incubated at 35°C. Viruses were initially identified by cytopathic effect and hemadsorption. Cultures without cytopathic effect or hemadsorption at 10 days were screened further by immunofluorescent assay. The CDC laboratory performed RT-PCR to detect RSV, influenza virus types A and B, PIV types 1 to 3, human metapneumovirus, and picornaviruses (not further characterized as enterovirus or rhinovirus). RT-PCR assays were designed using fluorescence-labeled primers and automated capillary electrophoresis and GeneScan DNA fragment analysis for amplicon detection. Specimens were designated PCR positive when the same amplification product was found in a second independent RT-PCR using a duplicate specimen aliquot. As previously described,¹¹ the RT-PCR procedures were highly reproducible, sensitive, and specific. A specimen was defined as virus positive when 1 viral culture or 2 independent RT-PCR tests were positive.

Demographic and Clinical Information

Demographic information, symptom duration, history of underlying medical conditions, exposure to tobacco smoke, number of children in the household, breastfeeding, child care attendance, influenza vaccination status, palivizumab administration, and antiviral medications were collected from parent/guardian interview. History of underlying medical conditions, health insurance status, admission diagnoses, microbiology and chest radiograph results, hospital course, and discharge diagnoses were obtained from medical chart review. A maximum of 10 International Classification of Diseases, Ninth Revision discharge diagnosis codes were recorded for each hospitalization, on the basis of diagnoses recorded and coded by nonstudy hospital coding staff. Medical conditions for which influenza vaccine is routinely recommended (heart disease, chronic pulmonary disease, kidney disease, cancer, diabetes, immunodeficiency, and sickle cell anemia) were included.

Data Analysis

Study Population

Rates of Hospitalization Associated With RSV, Influenza, and Parainfluenza Viruses

One third of enrolled children had 1 of the 3 targeted viral pathogens: 116 (20%) were positive for RSV, 20 (3%) were positive for influenza, and 40 (7%) were positive for PIV. Other viruses were identified in 36% (25 adenoviruses, 19 human metapneumoviruses, and 178 picornaviruses), and no viruses were detected in 39%. Several specimens were positive for >1 virus, but no enrolled child had multiple hospitalizations in which RSV, influenza virus, or PIV were detected. RSV- and influenza-associated hospitalizations overlapped, both peaking in January and February 2001. Influenza isolates were type A (H1N1) and type B, the predominant influenza types circulating in the United States.²¹ PIV hospitalizations were distributed throughout the year, consistent with other reports²² (Fig 1).

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Fig 1.

Number of enrolled hospitalizations for ARI by date of hospital admission, by virus cause. There were 18 cases of PIV-1 from February to September, 4 cases of PIV-2 from October to January, 17 cases of PIV-3 from October to August (71% occurred between February and May), and 1 case of PIV-4 in August.

Virus-positive hospitalization rates per 1000 children were 3.5 for RSV, 1.2 for PIV, and 0.6 for influenza virus (Table 2). Rates were not significantly different in the 2 counties (Fig 2), although overall ARI hospitalization rates in Davidson County were 50% higher than those in Monroe County as a result of higher rates of other viruses and virus-negative samples.

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Fig 2.

Population-based rates of hospitalization for ARI by age for the 2 counties, by virus cause. A, All ARI hospitalizations. B, Cause-specific hospitalizations.

Infants who were younger than 6 months accounted for more than half of the RSV hospitalizations and ∼40% of other hospitalizations. Of the targeted viral pathogens identified, 94% of RSV, 80% of influenza, and 85% of PIV were detected in children younger than 2 years (Fig 3). Rates of influenza- and PIV-associated hospitalizations were higher for non-Hispanic black and Hispanic children. In contrast, RSV-related hospitalizations did not differ by race or ethnicity. Non-Hispanic white children were significantly more likely to have private health insurance (60% vs 20%; P < .001), to have a sibling (81% vs 73%; P = .02), and to have a sibling older than 5 years (50% vs 33%; P < .001). Non-Hispanic white children were also less likely to have a high-risk condition (27% vs 36%; P = .03). Children with chronic underlying medical conditions were severalfold more likely to be hospitalized for 1 of the targeted viruses (Table 3), and overall hospitalization rates were higher for boys than for girls.

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Fig 3.

Age distribution of hospitalized children with ARI, by viral cause.

Clinical Findings in Children With RSV, Influenza Virus, and PIV

The most common admission diagnoses included fever, rule-out sepsis, or febrile seizure (39%); pneumonia (17%); asthma (17%); and bronchiolitis (16%). A significantly higher percentage of influenza-confirmed cases had an admission diagnoses of fever, rule-out sepsis, or febrile seizure compared with other viruses (65% vs 38%; P = .01). A significantly higher percentage of RSV-confirmed cases required supplemental oxygen compared with PIV or influenza cases (61% vs 27% and 30%, respectively; P < .001). The median length of stay for RSV-, PIV-, or influenza associated-hospitalizations was 2 days and did not differ among the viruses. Thirty-one children were admitted to the intensive care unit (5 RSV, 1 PIV, 0 influenza)

On the basis of discharge diagnoses, of the RSV cases, 79% had bronchiolitis and 27% had pneumonia, which were significantly higher than for other causes (P < .05). By comparison, 25% of PIV cases had bronchiolitis and 10% had pneumonia; 20% of influenza cases had bronchiolitis and 5% pneumonia.