To estimate the rates of hospitalization with seasonal influenza in children aged <18 years from a large, diverse surveillance area during 2003 to 2008.
Through the Emerging Infections Program Network, population-based surveillance for laboratoryconfirmed influenza was conducted in 10 states, including 5.3 million children. Hospitalized children were identified retrospectively; clinicians made influenza testing decisions. Data collected from the hospital record included demographics, medical history, and clinical course. Incidence rates were calculated with census data.
The highest hospitalization rates occurred in children aged <6 months (seasonal range, 9-30/10 000 children), and the lowest rates occurred in children aged 5 to 17 years (0.3-0.8/10 000). Overall, 4015 children were hospitalized, 58% of whom were identified with rapid diagnostic tests alone. Forty percent of the children who were hospitalized had underlying medical conditions; asthma (18%), prematurity (15% of children aged <2 years), and developmental delay (7%) were the most common. Severe outcomes included intensive care unit admission
(12%), respiratory failure (5%), bacterial coinfection (2%), and death (0.5%).
Influenza-associated hospitalization rates varied by season and age and likely underestimate true rates because many hospitalized children are not tested for influenza. The proportion of children with severe outcomes was substantial across seasons. Quantifying incidence of influenza hospitalization and severe outcomes is critical to defining disease burden.
(J Pediatr 2010;157:808-14) .
808
I nfluenza is a common cause of hospitalization in children in the United States, but estimates of seasonal influenza hospitalization rates have varied widely according to study methods and the influenza season. Previously, influenza in the pediatric population was estimated to result in influenza-associated hospitalization rates of 18 to 104 per 10 000 children aged <6
months,
1-3
9 to 30 per 10 000 children aged 6 to 23 months,
3-6
2 to 8 per 10 000 children aged 2 to 4 years,
3-5,7
and <1 to 2 per 10
000 children aged 5 to 17 years.
8,9
Some of these estimates were based on modeling techniques or indirect measures of influenza
because diagnostic testing for influenza was not widely available and use of rapid testing was limited or non-existent,
2,9-12
and other estimates were based on identification of children with laboratory-confirmed influenza during limited numbers of seasons or from a few sites.
1,3, 6-8,13,14
Because influenza disease burden can vary from season to season and across broad geographic areas, monitoring the incidence and clinical characteristics of influenza-related hospitalizations for multiple seasons and in multiple sites is critical to understanding the influenza disease burden in children, measuring the impact of current prevention programs, and guiding future prevention and treatment strategies. To our knowledge, no study to date has evaluated a large, multi-center, geographically diverse population of children aged through 17 years who were hospitalized with laboratory-confirmed seasonal influenza during multiple influenza seasons. With data from the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program (EIP) population-based surveillance for children hospitalized with laboratory-confirmed influenza collected during 5 consecutive influenza seasons in 10 US states, this analysis estimates rates of hospitalization with laboratory-confirmed seasonal influenza virus infection in children aged through 17 years and describes the demographic and clinical characteristics of this population.
CDC Centers for Disease Control and Prevention
From the Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA (F.D., A.F., L.K., A.B., L.F.);
California Emerging Infections Program, Oakland, CA
(A.R.); Colorado Department of Public Health and
Environment, Denver, CO (K.G.); Connecticut Emerging
Infections Program, Yale University, New Haven, CT
(J.M., J.H.); Georgia Emerging Infections Program,
Georgia Department of Human Resources, Division of
Public Health, Atlanta, GA (K.A.); Maryland Department of Health and Mental Hygiene, Baltimore, MD (P.R.);
Minnesota Department of Health, St. Paul, MN (R.L.,
C.M.); New Mexico Department of Health, Santa Fe, NM
(M.M., J.B.); Emerging Infections Program, New York
State Department of Health, Albany, NY (S.Z.);
Department of Medicine, University of Rochester School of Medicine and Dentistry and Monroe County
Department of Public Health, Rochester, NY (N.B.);
Oregon Public Health Division, Portland, Oregon (A.T.); and Department of Preventive Medicine, Vanderbilt
University School of Medicine, Nashville, TN (W.S., D.K.)
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. The authors declare no conflicts of interest.
EIP Emerging Infections Program 0022-3476/$ - see front matter. Copyright Ó 2010 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2010.05.012

Vol. 157, No. 5 November 2010
Influenza-associated hospitalization surveillance data were analyzed from 5 consecutive influenza seasons from 2003 to 2008. Surveillance was conducted through the CDC’s
EIP Network.
15
The EIP influenza surveillance catchment area expanded during the 6-year period. During the 2003 to 2004 influenza season, surveillance was conducted in these surveillance areas in 9 states: 5 Denver-area counties in Colorado; 11 towns in New Haven County, Connecticut; 8 counties in the metropolitan Atlanta area, Georgia; Baltimore
City and 5 surrounding counties, Maryland; 7 counties in the
Minneapolis area, Minnesota; 15 counties in the Rochester and Albany areas, New York; 3 counties in the Portland area, Oregon; 8 counties in the Nashville area, Tennessee; and Northern California Kaiser members in 3 San
Francisco-area counties. During the 2004 to 2005 season, surveillance was expanded to 10 states by including 1
Albuquerque-area county in New Mexico, and the surveillance area in Connecticut was expanded to all of New Haven.
During the 2005 to 2006 season, surveillance in California was expanded to all children aged <2 years in 3 San
Francisco-area counties in addition to all Kaiser members aged <18 years in those counties. During the 2006 to 2007 season, surveillance in California was expanded to all pediatric residents of the 3 San Francisco-area counties. During the
2007 to 2008 season, 1 Roswell-area county and 1 Santa
Fe-area county were added to the surveillance area in New
Mexico. The 2007 to 2008 surveillance area included approximately 5.3 million children aged <18 years (accounting for
7% of the United States population of children aged <18 years) and 149 hospitals serving almost all the pediatric population in the surveillance areas in 10 states.
A case was defined as a child aged <18 years residing in the surveillance area who was hospitalized in a surveillance area hospital with laboratory confirmation of influenza virus infection within 14 days of hospitalization from the 2003 to
2004 through 2007 to 2008 influenza seasons. Laboratory testing for influenza was ordered at the discretion of clinicians providing clinical care. Laboratory confirmation was defined as a positive result from viral culture, direct or indirect fluorescent antibody staining, rapid antigen test, or reverse transcriptase polymerase chain reaction.
Cases were identified prospectively through statemandated disease reporting systems or retrospectively through review of admission or discharge logs, hospital laboratory lists, and infection control logs from October 1 through April 30 of each influenza season. For each identified case, data were collected from the patient’s medical record.
Data collected included: demographic characteristics, medical history including underlying medical conditions, influenza immunization status, clinical course, and treatment with antiviral medications. When immunization status was not recorded in the medical record, this information was obtained from the patient’s parent/guardian, primary care provider, or state immunization registry.
Prematurity was considered a pre-existing medical condition when a child was born at <37 weeks gestation and aged
<2 years. A child was considered immunosuppressed when he/she had received immunosuppressive therapy in the 2 weeks before admission or had immunoglobulin deficiency, leukemia, lymphoma, or human immunodeficiency virus/acquired immunodeficiency syndrome. Treatment with steroids was considered to be an immunosuppressive therapy when a child received oral or injectable steroids for a minimum of 2 weeks before admission. Length of hospitalization was calculated by subtracting the admission date from the discharge date and adding 1 day, so that a patient who was admitted and discharged on the same date had a length of hospitalization of 1 day.
Data about bacterial co-infections were collected for each case. Bacterial co-infection was defined as growth of a bacterial pathogen from a normally sterile site (eg, blood, cerebrospinal fluid, pleural fluid, or tissue specimen) during the 2003 to 2006 seasons and was expanded to include non-sterile sites, namely, endotracheal aspirate, or sputum during the
2006 to 2008 seasons.
Staphylococcus epidermidis and Propioni bacterium species were considered pathogens only when isolated from a cerebrospinal fluid culture or from a specimen from a neonate aged <28 days or a child who was immunosuppressed. A case of influenza-associated pneumonia was defined as any hospitalized child with laboratory-confirmed influenza who had evidence of a new pneumonia (ie, a pneumonia not identified on chest radiograph before the current admission when earlier chest radiographs were obtained) on at least 1 chest radiograph obtained during the current admission or hospitalization. Children were included when they had evidence of pneumonia on a chest radiograph obtained during the current admission or hospitalization, but did not have an earlier chest radiograph for comparison.
The nature of this data collection has been determined by
CDC to be for routine public health surveillance purposes and is not subject to institutional review board approval for human research protections.
Statistical Analysis
Incidence rates were calculated for each influenza season with data from Northern California Kaiser annual membership for the surveillance areas in California and data from the
US Bureau of the Census and the National Center for Health
Statistics from the year in which the influenza season began for all other surveillance areas. Denominators used for incidence rate calculations reflect the population of the catchment areas for hospitals participating in the surveillance system each season and were adjusted as the surveillance area expanded during 2003 to 2008. Incidence for children aged <6 months was calculated by using denominators derived by dividing the population of children in the surveillance area who were aged <1 year in half. Statistical analyses were conducted with SAS software version 9.1 (SAS Institute,
Cary, North Carolina).
809

T
HE
J
OURNAL OF
P
EDIATRICS www.jpeds.com
Vol. 157, No. 5
Rates of Hospitalization
A total of 4015 laboratory-confirmed influenza hospitalizations in children aged <18 years were identified from 2003 to 2008.
Overall, rates of hospitalization for children ranged from 1 per 10 000 children during the 2006 to 2007 influenza season to 3 per 10 000 children during the 2003 to 2004 influenza sea-
son ( Figure
). The highest rates of hospitalization occurred in children aged <6 months (range, 9-30 per 10 000 children per year), and the lowest rates occurred in children aged 5 to
17 years (range, 0.3-0.8 per 10 000 children).
Demographic Characteristics and Pre-existing
Medical Conditions
On average, 40% of hospitalized children had $ 1 underlying medical condition that confer a higher risk for severe influenza, as currently defined by the Advisory Committee on Immunization Practices (
Table I ).
16
Underlying medical conditions were more common in children aged 5 to 17 years than children aged <5 years (63%-77% versus 33%-
37%, P < .01). In hospitalized children aged <5 years, asthma (12%) was the most common underlying medical condition, followed by a history of prematurity (11% of children aged <5 years; 15% of children aged <2 years), and developmental delay (6%). In hospitalized children aged $ 5 years, asthma (36%) was still the most common underlying medical condition, followed by developmental delay (12%), and neuromuscular disorders (9%).
Consistent with their higher rates of hospitalization, more than one-quarter of hospitalized children were aged <6 months (27%-29%), with most <5 years old (68%-80%;
Table II
). The median age of hospitalized children ranged from 1.5 years during the 2003 to 2004 season to 2.1 years during the 2004 to 2005 season.
Immunization status
Of hospitalized children who were aged $ 6 months, approximately one-third (29%-35%) had received at least 1 dose of influenza vaccine during the influenza season in which they were
hospitalized ( Table II ). Immunization with at least 1 dose of
influenza vaccine was more common in children aged 6 to
23 months (33%-41%) than in children aged 5 to 17 years
(23%-28%). Influenza immunization status was unknown for 10% to 17% of hospitalized children. Children aged 6 months to 8 years require 2 doses of influenza vaccine spaced at least 1 month apart during their first season of
influenza immunization to be considered fully immunized.
17
For children aged 6 months to 8 years, full immunization status was not determined because of incomplete data on the number of vaccine doses received during the current season.
Clinical Characteristics, Complications, and
Outcomes
Rapid influenza testing was the most common diagnostic test used as a means of diagnosing influenza virus infection
810
(62%-73%), followed by direct or indirect fluorescent antibody stain (14%-27%) and viral culture (10%-16%); reverse transcriptase polymerase chain reaction was used as a means of diagnosing influenza virus infection in only
1% to 5% of children. Influenza A (65%-82%) was the predominant influenza type identified during all 5 influenza seasons. The median length of hospitalization was 3 to 4 days. Bacterial co-infection was identified in 2% of hospitalized children.
Streptococcus pneumoniae was the most commonly identified pathogen during the 2003 to 2004 season, and Staphylococcus aureus was the most commonly identified bacterial pathogen during all subsequent seasons
( Table II ).
Seventy-five percent of children had a chest radiograph at some point during their hospitalization. Of children who underwent a chest radiograph, 32% to 38% had radiologic evidence of pneumonia. Between 11% and 14% of hospitalized children required intensive care unit admission, and 3% to
7% of children required mechanical ventilation. Less than
1% of children required extracorporeal membrane oxygenation during any influenza season. Encephalopathy was diagnosed in 2 to 8 children per season.
Seventeen deaths in children hospitalized with influenza occurred during the 5 influenza seasons. Of these, 3 children
(18%) were aged <6 months, 1 child (6%) was aged 6 to 23 months, 3 children (18%) were aged 2 to 4 years, and 10 children (59%) were aged 5 to 17 years. Nine children who died (53%) had an underlying medical condition, and 10 children who died (59%) had pneumonia diagnosed with an infiltrate on chest radiograph. Two children who died had evidence of bacterial co-infection (1 with S aureus and 1 with Enterococcus faecalis ). Of the 14 children who died who were eligible to receive influenza vaccine (ie, were aged 6 months or older), data were available on influenza immunization status and the number of influenza vaccine doses received during the current season for all 14 children. Only 3 of these children (21%) had received any influenza vaccine during the current season, and only 2 of the children (14%) were considered fully immunized (ie, had received 2 doses when in the first season of immunization), including a 9-month-old child with a history of prematurity, developmental delay, and neurologic disorder and a 15-year-old child with cerebral palsy.
Treatment with Antiviral Medications
Of children aged $ 1 year who had positive results on an influenza diagnostic test within 48 hours of symptom onset, fewer than half were treated with antiviral medications during their hospital stay (37%-48%). The proportion of children treated with adamantanes decreased in the 5 influenza seasons from 28% during the 2003 to 2004 influenza season to 1% during the 2007 to 2008 season. Among children aged
$ 1 year with underlying medical condition conferring higher risk for severe influenza and with positive results on at least one influenza diagnostic test within 48 hours of symptom onset, only 33% to 55% received antiviral treatment during their hospitalization.
Dawood et al

November 2010
Figure.
Rates of influenza-associated hospitalization by season, 2003-2008.
In this analysis, a population-based surveillance system identified >4000 children hospitalized with laboratory-confirmed influenza from geographically diverse areas of the United
States. This analysis provides a current estimate of the burden of influenza in children across multiple influenza seasons, identifies children at risk for influenza-associated hospitalization, describes testing and treatment practices for hospitalized children, and establishes a baseline for estimating the impact of prevention programs.
Rates of influenza-associated hospitalization in children varied as much as 3-fold from season to season, illustrating the need for multi-season surveillance. Of the 5 influenza seasons in this analysis, the 2003 to 2004 season has been regarded as the most severe season, during which influenza
A (H3N2) viruses similar to the drifted variant A/Fujian/
411/2002 predominated in the United States, physician office visits for influenza-like illness in adults were much higher than subsequent seasons, deaths attributed to pneumonia and influenza peaked at 10.3% of all adult deaths, and an unprecedented number of influenza-associated pediatric deaths were reported to the CDC.
18,19
In contrast, the 2006 to 2007 season has been regarded as the least severe, during which influenza A (H1N1) viruses similar to the 2006 to 2007 influenza A (H1N1) vaccine component A/New Caledonia/20/
99 predominated in the United States, physician office visits for influenza-like illness were relatively low, and deaths
Table I.
Underlying medical conditions among children hospitalized with laboratory-confirmed influenza, 2003 to 2008,
(N = 4015)
2003-04 2004-05 2005-06 2006-07 2007-08 All seasons
Total cases, n
One or more underlying medical conditions, n (%)
Asthma
Cardiovascular disease
Chronic lung disease
Chronic metabolic disease
Cystic fibrosis
Developmental delay
Febrile seizures
Hemoglobinopathy
Immunosuppressive condition
Neuromuscular disorder
Prematurity
†
Renal disease
Seizure disorder
1306
559 (43%)
231 (18%)
27 (2%)
29 (2%)
14 (1%)
6 (<1%)
*
*
44 (3%)
25 (2%)
*
*
6 (<1%)
55 (4%)
615
280 (46%)
117 (19%)
23 (4%)
17 (3%)
11 (2%)
8 (1%)
52 (8%)
13 (2%)
22 (4%)
28 (5%)
30 (5%)
42 (7%)
11 (2%)
33 (5%)
712
325 (46%)
132 (19%)
20 (3%)
27 (4%)
20 (3%)
2 (<1%)
55 (8%)
8 (1%)
19 (3%)
33 (5%)
38 (5%)
77 (11%)
17 (2%)
31 (4%)
523
223 (43%)
81 (16%)
20 (4%)
31 (6%)
25 (5%)
1 (<1%)
35 (7%)
6 (1%)
17 (3%)
25 (5%)
26 (5%)
52 (10%)
10 (2%)
22 (4%)
859
507 (59%)
165 (19%)
28 (3%)
19 (2%)
23 (3%)
3 (<1%)
49 (6%)
12 (1%)
28 (3%)
41 (5%)
18 (2%)
48 (6%)
13 (2%)
39 (5%)
4015
1894 (47%)
726 (18%)
118 (3%)
123 (3%)
93 (2%)
20 (<1%)
191 (7%)
39 (1%)
130 (3%)
152 (4%)
112 (4%)
219 (8%)
57 (1%)
180 (4%)
*Not evaluated during season.
†Gestational age <37 weeks at birth for patients aged<2 years.
Burden of Seasonal Influenza Hospitalization in Children, United States, 2003 to 2008 811

T
HE
J
OURNAL OF
P
EDIATRICS www.jpeds.com
Vol. 157, No. 5
Table II.
Demographic and clinical characteristics of children hospitalized with laboratory-confirmed influenza, 2003 to
2008, (N = 4015)
Characteristic 2003-04 2004-05 2005-06 2006-07 2007-08 All seasons
Total cases, n
Male sex, n (%)
Age, n (%)
<6 months
6-23 months
2-4 years
5-17 years
Race/Ethnicity, n (%)
Caucasian
African-American
Asian
Hispanic
Other
Unknown
Vaccination status, n (%)
At least 1 dose influenza vaccine *
Unknown
Flu subtype, n (%)
A
B
Unknown
Bacerial co-infection, n (%)
†
Streptococcus pneumoniae
Group A Streptococcus
Haemophilus influenzae
Staphyloccocus aureus
Other z
Chest radiograph, n (%)
Pneumonia, n (%) x
ICU hospitalization, n (%)
Mechanical ventilation, n (%)
Death, n (%)
Antiviral class, n (%)
{
Adamantane
Neuraminidase inhibitor
1306
748 (57%)
357 (27%)
413 (32%)
276 (21%)
260 (20%)
510 (39%)
355 (27%)
31 (2%)
246 (19%)
25 (2%)
179 (14%)
278 (29%)
159 (17%)
995 (76%)
5 (<1%)
306 (23%)
25 (2%)
4
0
3
2
16
975 (75%)
368 (38%)
148 (11%)
45 (3%)
5 (<1%)
174/362 (48%)
100 (28%)
74 (20%)
615
350 (57%)
166 (27%)
136 (22%)
119 (19%)
194 (32%)
247 (40%)
154 (25%)
23 (4%)
125 (20%)
2 (<1%)
73 (12%)
158 (35%)
55 (12%)
401 (65%)
157 (26%)
57 (9%)
15 (2%)
1
5
7
2
0
428 (70%)
135 (32%)
76 (12%)
34 (6%)
4 (1%)
95/205 (46%)
27 (13%)
68 (33%)
712
399 (56%)
205 (29%)
198 (28%)
122 (17%)
187 (26%)
282 (40%)
167 (23%)
27 (4%)
156 (22%)
7 (1%)
113 (16%)
151 (30%)
88 (17%)
552 (78%)
130 (18%)
30 (4%)
13 (2%)
2
5
4
2
0
544 (76%)
196 (36%)
96 (13%)
47 (7%)
5 (1%)
106/226 (46%)
5 (2%)
100 (44%)
523
316 (60%)
141 (27%)
150 (29%)
102 (19%)
130 (25%)
212 (41%)
118 (23%)
14 (3%)
151 (29%)
2 (<1%)
57 (11%)
130 (34%)
42 (11%)
428 (82%)
72 (14%)
23 (4%)
5 (1%)
0
2
3
0
0
420 (80%)
161 (38%)
71 (14%)
35 (7%)
2 (<1%)
67/178 (38%)
1 (1%)
66 (37%)
859
475 (55%)
252 (29%)
220 (26%)
166 (19%)
221 (26%)
364 (42%)
214 (25%)
45 (5%)
192 (22%)
12 (1%)
75 (9%)
197 (32%)
62 (10%)
604 (70%)
181 (21%)
74 (9%)
18 (2%)
4
2
0
10
2
626 (73%)
212 (34%)
95 (11%)
47 (5%)
1 (<1%)
110/297 (37%)
1 (1%)
109 (36%)
4015
2288 (57%)
1121 (28%)
1117 (28%)
785 (19%)
992 (25%)
1615 (40%)
1008 (25%)
140 (3%)
870 (22%)
48 (1%)
497 (12%)
914 (32%)
406 (14%)
2980 (74%)
545 (14%)
490 (12%)
76 (2%)
11
6
3
24
32
2993 (75%)
1072 (36%)
486 (12%)
208 (5%)
17 (<1%)
552/1268 (44%)
134 (11%)
417 (33%)
*Of children aged $ 6 months eligible to receive influenza vaccine.
†Sputum and endotracheal aspirate cultures included in 2006 to 2008 data only.
z Other than Streptoccocus pneumoniae, Group A Streptococcus, Haemophilus influenzae, and Staphylococcus aureus.
x Of those who underwent chest radiography.
{ Of children aged $ 1 year with symptom onset within 48 hours of positive results on influenza diagnostic test.
attributed to pneumonia and influenza peaked at 7.7% of all
adult deaths.
20
In this analysis, annual rates of pediatric influenza-associated hospitalization were consistent with the overall severity of the season. However, even during the mildest season of 2006 to 2007, the incidence of influenzaassociated complications in hospitalized children remained consistently high, with 38% of all children who had a chest radiography during admission having radiologically defined pneumonia, 14% requiring intensive care unit admission, and 7% developing respiratory failure requiring mechanical ventilation.
Despite seasonal variation in influenza severity, certain groups of children were consistently at higher risk for influenza-associated hospitalization. Children aged <6 months had the highest rates of hospitalization across all sea-
sons, consistent with the findings of earlier studies.
1-3,6
Because influenza vaccine is not approved for children aged
<6 months, influenza immunization of household contacts, out- of-home caregivers of children in this age group, and pregnant women remains the primary way to reduce the risk of influenza in young infants. Immunization of women
812 who are or will become pregnant during influenza season has been endorsed by the American College of Obstetricians
and Gynecologists since 2004.
21
Additionally, a recent randomized controlled trial in Bangladesh demonstrated a significant decrease in laboratory-confirmed influenza during the first 6 months of life in infants born to women immunized
against influenza during pregnancy.
22
Children with at least one pre-existing high risk medical condition constituted approximately half the hospitalized children in this analysis; asthma (18%), prematurity (8%), and developmental delay (7%) were the most common conditions. In comparison, estimates of the prevalence of chronic conditions in children in the United States indicate that 10% of children have asthma
23
and 3% of children have developmental delay.
24
These findings provide additional evidence that many children with chronic medical conditions are at higher risk for severe influenza. However, despite long-standing recommendations for vaccinating children with chronic medical conditions, immunization coverage remains low and largely unchanged.
25,26
As of the 2008 to 2009 influenza season, the Advisory Committee on Immunization
Dawood et al

November 2010
Practices now recommends that all children aged 6 months through 18 years receive influenza immunization, removing the need for pediatric healthcare providers to screen pediat-
ric patients to determine eligibility for influenza vaccine.
17
Although further studies on the effectiveness of antiviral treatment in preventing complications of influenza are needed, existing studies demonstrate that treatment with oseltamivir in previously healthy individuals may reduce illness duration, severity of symptoms, and risk for pneumonia when initiated within 48 hours of illness onset,
27-29
and treatment of children with asthma may reduce the duration of illness and improve pulmonary function during the illness period.
30
Severely ill children may also benefit from antiviral treatment even when >48 hours have elapsed since illness onset.
31
Since 2007, the American Academy of Pediatrics has recommended antiviral treatment of influenza in children with high-risk medical conditions and any child with moderate-to-severe influenza who may benefit from a reduction in illness duration.
32
Antiviral medications have been licensed for use in children aged $ 1 year for many years, and in April 2009, in response to the 2009 influenza pandemic, the Food and Drug Administration issued an Emergency-
Use Authorization ( http://www.cdc.gov/h1n1flu/eua/tamiflu.
htm ) approving the use of oseltamivir in children aged <1 year. In the EIP surveillance areas, during 2003 to 2008, most children who were hospitalized with a positive influenza diagnostic test within 48 hours of illness onset did not receive antiviral medications. Treatment rates did not increase with time despite data on the benefits of early treatment with antiviral medications. These findings indicate that additional education might increase clinicians’ awareness of evidence for antiviral effectiveness and current influenza treatment recommendations.
This analysis had several limitations. First, through EIP surveillance, cases of laboratory-confirmed influenza diagnosed by healthcare provider-initiated diagnostic testing are identified, but prospective routine testing of all children hospitalized with respiratory illness does not occur. Fifty-eight percent of cases in this analysis were identified only by rapid influenza diagnostic tests that have variable sensitivity ranging from
50% to 70%,
33
and overall age-adjusted rates of influenzaassociated hospitalization varied substantially across EIP states. Variability in hospitalization rates derived from EIP surveillance has been shown to correlate with influenza testing
practices in emergency department clinicians in a given area.
34
In addition, an evaluation of EIP surveillance in children aged
<5 years hospitalized with laboratory-confirmed influenza during the 2004 and 2005 season determined that the sensitivity of the EIP system for detecting influenza in hospitalized patients was 39%, and that a substantial number of cases were missed because of a lack of testing or false-negative test results.
5
Thus, the estimated rates of influenza-associated hospitalization presented in this analysis are likely lower than actual rates, and EIP surveillance may be more likely to identify children with more severe illness because such children may be more likely to be tested for influenza. Increased use of molecular diagnostic techniques such as reverse transcriptase-polymerase chain reaction for influenza diagnostic testing would increase the sensitivity of surveillance systems designed to capture influenza disease burden in the future. Second, EIP surveillance likely underestimates the incidence of bacterial co-infection because it relies on providerinitiated bacterial cultures and includes only children with invasive bacterial infections or children in whom a bacterial pathogen was isolated from endotracheal tube aspirate or sputum culture. Third, full immunization status could not be determined for children aged 6 months to 8 years of age in this analysis because data on the number of influenza vaccine doses received during the current season and influenza immunization during earlier seasons were incomplete. Lastly, lack of immunization coverage data-specific to the EIP surveillance area, changes in annual immunization recommendations during the analysis period, and seasonal variation in vaccine match to circulating influenza strains and influenza vaccine effectiveness make it difficult to attribute variation in influenzaassociated hospitalization rates to changes in influenza immunization coverage in this analysis.
n
The authors would like to thank Monica Farley, Kyle Openo, Magan
Pearson, Suzanne Segler.
Submitted for publication Dec 9, 2009; last revision received Mar 22, 2010; accepted May 5, 2010.
Reprint requests: Fatimah S. Dawood, Epidemic Intelligence Service Officer assigned to the Influenza Division, Centers for Disease Control and Prevention,
1600 Clifton Rd MS A-32, Atlanta, GA 30333. E-mail: fdawood@cdc.gov
.
1.
Griffin M, Walker F, Iwane M, Weinberg G, Staat MA, Erdman D.
Epidemiology of respiratory infections in young children: insights from the new vaccine surveillance network. Pediatr Infect Dis J
2004;23:188-92.
2.
Neuzil K, Mellen B, Wright P, Mitchel E, Griffin M. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342:225-31.
3.
Poehling K, Edwards K, Weinberg G, Szilagyi P, Staat MA, Iwane M, et al. The underrecognized burden of influenza in young children. N
Engl J Med 2006;355:31-40.
4.
Grijalva C. Estimating influenza hospitalizations among children. Emerg
Infect Dis 2006;12:103-9.
5.
Grijalva C, Weinberg G, Bennett NM, Staat MA, Craig AS. Estimating the undetected burden of influenza hospitalizations in children. Epidemiol Infect 2007;135:951-8.
6.
Schrag S, Shay D, Gershman K, Thomas A, Craig A, Schaffner W, et al.
Multistate surveillance for laboratory-confirmed, influenza-associated hospitalizations in children, 2003-2004. Pediatr Infect Dis J 2006;25:
395-400.
7.
Coffin S, Zaoutis T, Rosenquist A, Heydon K, Herrera G, Bridges C, et al.
Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics 2007;119:
740-8.
8.
Ampofo K, Gesteland P, Bender J, Mills M, Daly J, Samore M, et al.
Epidemiology, complications, and cost of hospitalization in children with laboratory-confirmed influenza infection. Pediatrics 2006;118:
2409-17.
9.
Izurieta H, Thompson W, Kramarz P, Shay D, Davis R, DeStefano F, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-9.
Burden of Seasonal Influenza Hospitalization in Children, United States, 2003 to 2008 813

T
HE
J
OURNAL OF
P
EDIATRICS www.jpeds.com
Vol. 157, No. 5
10.
Neuzil K, Wright P, Mitchel E, Griffin M. The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr
2000;137:856-64.
11.
O’Brien M, Uyeki T, Shay D, Thompson W, Kleinman K, McAdam A.
Incidence of outpatient visits and hospitalizations related to influenza in infants and young children. Pediatrics 2004;113:585-93.
12.
Schanzer D, Langley J, Tam T. Hospitalization attributable to influenza and other viral respiratory illnesses in Canadian children. Pediatr Infect
Dis J 2006;25:795-800.
13.
Griffin M, Coffey C, Neuzil K, Mitchel E, Wright P, Edwards K. Influenza- and respiratory-syncytial virus-related morbidity in chronic lung disease. Arch Int Med 2002;162:1229-36.
14.
Iwane M, Edwards K, Szilagyi P, Walker F, Griffin M, Weinberg G, et al.
Population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children. Pediatrics 2004;113:1758-64.
15.
Pinner RW, Rebmann CA, Schuchat A, Hughes JM. Disease surveillance and the academic, clinical, and public health communities. Emerg Infect
Dis 2003;9:781-7.
16.
Fiore A, Shay D, Penina H, Iskander J. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization
Practices (ACIP), 2007. Mor Mortal Wkly Rep 2007;56:1-54.
17.
Fiore A, Shay D, Broder K, Iskander J, Uyeki T, Mootrey G, et al. Influenza prevention and control: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mor Mortal Wkly Rep
2008;57:1-60.
18.
Update: influenza activity—United States, 2003-04 season. Mor Mortal
Wkly Rep 2004;53:284-7.
19.
Bhat N, Wright J, Broder K, Murray E, Greenberg M, Glover M, et al. Influenza-associated deaths among children in the United States, 2003-
2004. N Engl J Med 2005;353:2559-66.
20.
Update: influenza activity—United States and worldwide, 2006-07 season, and composition of the 2007-08 influenza vaccine. Mor Mortal
Wkly Rep 2007;56:789-94.
21.
American College of Obstetrics and Gynecology. Influenza vaccination and treatment during pregnancy. Obstet Gynecol 2004;104:1125-6.
22.
Zaman K, Roy E, Arifeen S, Rahman M, Raqib R. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008;
359:1555-64.
23.
Bloom B, Cohen RA, Freeman G. Summary health statistics for US children: National Health Interview Survey, 2008. Vial Health Stat 10 2009;
244:1-81.
24.
Simpson G, Colpe L, Greenspan S. Measuring functional developmental delay in infants and young children: prevalence rates from the NHIS-D.
Paediatr Perinat Epidemiol 2003;17:68-80.
25.
Williams L, Fiore A, White K. Influenza vaccination coverage among children aged 6-59 months—eight Immunization Information System sentinel sites, United States, 2007-08 influenza season. Mor Mortal
Wkly Rep 2008;57:1043-6.
26.
Ligon C, Rudd R, Callahan D, Euler G. Influenza vaccination coverage among persons with asthma–United States, 2005-06 influenza season.
Mor Mortal Wkly Rep 2008;57:653-7.
27.
Aoki F, McLeod M, Paggiaro P. Early Administration of oral oseltamivir increases the benefit of influenza treatment. J Antimicrob Chemother
2003;51:123-9.
28.
Barr C, Schulman K, Iacuzio D. Effect of oseltamivir on the risk of pneumonia and use of health care services in children with clinically diagnosed influenza. Curr Med Res Opin 2007;23:523-31.
29.
Whitley R, Hayden F, Reisinger K, Young N, Dutkowski R. Oral oseltamivir treatment of influenza in children. J Pediatr Infect Dis 2001;20:
127-33.
30.
Johnston S, Ferrero F, Garcia M. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma. J Pediatr Infect Dis 2005;24:225-32.
31.
Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season.
2009. Available at http://www.cdc.gov/H1N1flu/recommendations.
htm . Accessed Feb 14, 2010.
32.
American Academy of Pediatrics Committee on Infectious Diseases. Antiviral therapy and prophylaxis for influenza in children. Pediatrics 2007;
119:852-60.
33.
Rapid diagnostic testing for influenza. Available at http://www.cdc.gov/ flu/professionals/diagnosis/rapidlab.htm
. Accessed Mar 9, 2010.
34.
Mueller M, Baumbach J, Daily Kirley P, Aragon K, Gershman J. Influenza testing practices in the emergency department: correlation with laboratory-confirmed influenza hospitalization rates, emerging infections program, 2006-2007 influenza season. In: International Conference on Emerging Infectious Diseases, Atlanta, GA; 2008.
814 Dawood et al