PEDIATRICS Vol. 119 No. 4 April 2007, pp. 740-748 (doi:10.1542/peds.2006-2679)
ARTICLE |
Incidence, Complications, and Risk Factors for Prolonged Stay in Children Hospitalized With Community-Acquired Influenza
f Divisions of General Pediatrics
a Infectious Diseases
e Department of Anatomic Pathology and Clinical Laboratories, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
d Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
c Department of Public Health
b National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVES. Few studies have examined the characteristics and clinical course of children hospitalized with laboratory-confirmed influenza. We sought to (1) estimate the age-specific incidence of influenza-related hospitalizations, (2) describe the characteristics and clinical course of children hospitalized with influenza, and (3) identify risk factors for prolonged hospitalization.
PATIENTS AND METHODS. Children 
21 years of age hospitalized with community-acquired laboratory-confirmed influenza at a large urban children's hospital were identified through review of laboratory records and administrative data sources. A neighborhood cohort embedded within our study population was used to estimate the incidence of community-acquired laboratory-confirmed influenza hospitalizations among children <18 years old. Risk factors for prolonged hospitalization (>6 days) were determined by using logistic regression.
RESULTS. We identified 745 children hospitalized with community-acquired laboratory-confirmed influenza during the 4-year study period. In this urban cohort, the incidence of community-acquired laboratory-confirmed influenza hospitalization was 7 per 10000 child-years of observation. The median age was 1.8 years; 25% were infants <6 months old, and 77% were children <5 years old. Many children (49%) had a medical condition associated with an increased risk of influenza-related complications. The incidence of influenza-related complications was higher among children with a preexisting high-risk condition than for previously healthy children (29% vs 21%). However, only cardiac and neurologic/neuromuscular diseases were found to be independent risk factors for prolonged hospitalization.
CONCLUSIONS. Influenza is a common cause of hospitalization among both healthy and chronically ill children. Children with cardiac or neurologic/neuromuscular disease are at increased risk of prolonged hospitalization; therefore, children with these conditions and their contacts should be a high priority to receive vaccine. The impact on pediatric hospitalization of the new recommendation to vaccinate all children 6 months to <5 years old should be assessed.
Key Words: influenza • child • epidemiology
Abbreviations: LCI—laboratory-confirmed influenza • CA—community-acquired • CHOP—Children's Hospital of Philadelphia • ICD-9—International Classification of Diseases, Ninth Revision • SPIA—solid-phase immunoassay • DFA—direct fluorescent antibody assay • ACIP—Advisory Committee on Immunization Practices • NNMD—neurologic or neuromuscular disease • CDC—Centers for Disease Control and Prevention • LOS—length of stay • CI—confidence interval • OR—odds ratio
Influenza is a common cause of illness in children. Although the burden of disease in children is incompletely understood, studies suggest that children with selected underlying medical conditions are at increased risk of hospitalization or complications associated with influenza virus infection.1–6 Over the past 4 years, public health officials have expanded the groups of children recommended to receive annual influenza immunization. Children now recommended to receive influenza vaccine include preschool-aged children ages 6 months to 5 years and children with underlying neurologic/neuromuscular disease.7,8 Debate continues about the need for and logistic impediments associated with extending influenza vaccination recommendations to all children.9,10
Although influenza is a relatively common cause of hospitalization among children during the winter months, few studies have described the characteristics of a large cohort of children with laboratory-confirmed influenza who require hospitalization. Previous studies of influenza-related hospitalizations, complications, and deaths in children have relied primarily on administrative data and have not been based on cases of laboratory-confirmed influenza (LCI). In this study, we used hospital laboratory results to identify all children with LCI. Detailed clinical data were obtained from electronic hospital billing records and systematic chart review of children hospitalized with community-associated (CA) LCI. In this report we (1) determined the age-specific incidence of hospitalization attributable to influenza, (2) described the clinical characteristics and complications of children hospitalized with influenza, and (3) identified risk factors for prolonged hospitalization attributable to influenza.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Design, Setting, and Patients
We conducted a retrospective cohort study of children hospitalized with CA LCI during 4 consecutive seasons (July 2000 through June 2004) at the Children's Hospital of Philadelphia (CHOP). CHOP is an academic, tertiary-care hospital with 418 patient beds and
24000 hospital admissions each year. At CHOP, hospitalized patients with acute respiratory symptoms of unclear etiology routinely undergo testing for respiratory viral pathogens to facilitate the appropriate cohorting of patients and assignment of nursing staff for infection control purposes. We have described previously the methods used for identifying cases of CA LCI during the study period.11 Briefly, we identified cases using both clinical virology laboratory records and hospital administrative data (influenza-specific International Classification of Diseases, Ninth Revision [ICD-9] admission or discharge codes 487, 487.0, 487.1, and 487.8). Patients identified by ICD-9 codes required laboratory confirmation to be included as subjects in the study cohort. As part of routine care at CHOP, nasal aspirate specimens were collected from children with acute respiratory symptoms of unclear etiology and were initially tested by solid-phase immunoassay (SPIA) for respiratory syncytial virus (Binax NOW RSV; Binax; Portland, ME) and influenza (Binax NOW FluA and FluB). Direct fluorescent antibody (DFA) testing for adenovirus, influenza A and B, parainfluenza virus types 1, 2, and 3, and respiratory syncytial virus was performed on specimens that tested negative by SPIA for respiratory syncytial virus and influenza A and B. Finally, comprehensive viral culture was established for all specimens that were negative for respiratory viruses on DFA.
Study Definitions
CA LCI
A patient was determined to have a health care-associated infection if the first diagnostic specimen positive for influenza was obtained >72 hours after hospital admission or if the patient was rehospitalized with new-onset LCI within 72 hours of discharge from a previous hospitalization; patients with health care-associated influenza were excluded from the analysis.
Chronic Medical Conditions
To identify preexisting chronic medical conditions that might predispose a child to serious influenza infection, we performed a detailed chart review to provide us with information about the presence of Advisory Committee on Immunization Practices (ACIP)–designated, high-risk medical characteristics as previously described,12 such as asthma, chronic lung diseases, cardiac disease, immunosuppression, hemoglobinopathies, chronic renal dysfunction, diabetes mellitus, and inborn errors of metabolism, long-term salicylate therapy, neurologic/neuromuscular disease (NNMD), and pregnancy. Infants <12 months of age were defined as premature if their estimated gestational age at birth was <36 weeks. For patients with multiple hospitalizations during the 4-year study period, we included only the first hospitalization in the analysis.
Major Complications
Complications among patients hospitalized with CA LCI were identified by using data from discharge summaries, consultants' reports, and billing records. Respiratory failure was defined as the need for mechanical ventilation. We identified patients who had altered mental status for >24 hours as having encephalopathy, consistent with the definition of influenza-related encephalopathy developed by the Centers for Disease Control and Prevention (CDC).12 In addition, patients with new-onset or increased frequency of seizures were also categorized as having influenza-related seizures. We defined myocarditis as new abnormalities of cardiac electrical or contractile function documented by a cardiologist. Myositis was defined by a peak serum creatine kinase concentration twofold greater than normal for age. Suspected bacterial pneumonia was identified if an attending radiologist read a chest radiograph as having a focal infiltrate or opacity or pleural effusion. Radiographs with diffuse interstitial infiltrates were not included in this category. Influenza-related bacteremia was identified if a patient had evidence of a laboratory-confirmed bloodstream infection based on definitions from the CDC13 within 48 hours of hospitalization. Prolonged hospital stay was defined as hospitalization for longer than 6 consecutive days, which corresponded to 2 SDs beyond the median length of stay (LOS).
Data Collection
Clinical data were retrieved by systematic review of the medical charts using a structured data collection instrument. Demographic and cost data were abstracted from hospital billing records and administrative data sets and validated as previously described.11
Clinical Data
The physician admission and discharge notes, physician discharge summary, laboratory and radiology records were searched for the following clinical variables: hospital discharge within 72 hours of current admission; presence of chronic conditions; and laboratory results, chest radiograph, and neuroimaging results. Notes from subspecialty consultants were also reviewed to identify possible influenza-related complications. Race and ethnicity are self-reported at the time of hospital registration and recorded by registrars using 4 categories of race and 2 categories of ethnicity. We collected information about race/ethnicity to assess the generalizability of our findings and to determine whether the study sample was reflective of the CHOP inpatient population.
Administrative Data
Demographic data collected included patient age and gender. The following clinical data were captured from administrative data sets: duration of hospitalization, need for admission to an ICU, mechanical ventilation, and radiographic and laboratory diagnostic testing.
To verify the accuracy of the administrative and billing data sources used to capture clinical variables, we conducted an audit of 10% of randomly selected records and compared data gathered from administrative sources with those obtained from chart review as previously described.11 Discrepant results were found in <3% of audited data points.
Estimation of Incidence of Pediatric Hospitalizations Because of Influenza
To estimate the incidence of pediatric hospitalizations attributable to CA LCI, a neighborhood cohort was defined. Administrative claims data from all acute care hospitals in Pennsylvania and New Jersey were queried (Solucient Corporation, New Orleans, LA) to identify zip-code areas with documented preferential admission to CHOP for acute asthma exacerbation (ICD-9 code 493.02 [extrinsic asthma, acute exacerbation]). Nine contiguous zip-code areas were identified from which >70% of all children <18 years of age who required hospitalization for asthma were admitted to the study hospital during the first 42 months of the 48-month study period. These zip-code areas with documented preferential admission to CHOP defined the neighborhood cohort (Table 1). Data from the US Census 2000 Factfinder were used to estimate the numbers of child-years of observation during the study period (July 2000 through June 2004). Age-specific estimates of child-years of observation were also obtained through the US Census Bureau Web site (www.census.gov).
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Statistical Methods
Descriptive Statistics
Descriptive analyses included calculating the means or medians with 95% confidence intervals (CIs) for continuous variables and the frequencies for categorical variables. Categorical variables were compared by using
2 or the Fisher's exact test, whereas continuous variables were compared by using the Wilcoxon rank-sum test. For categorical variables, odds ratios (ORs) and corresponding 95% CIs were derived. We used univariate logistic regression to estimate ORs and corresponding 95% CIs for the association between the independent and dependent variables.
Predictors of Prolonged Length of Hospital Stay
To identify additional risk factors associated with serious influenza infection, we examined the association between prolonged hospitalization and various demographic and clinical characteristics using multivariable logistic regression. We defined prolonged hospitalization as >6 days, which corresponded approximately to the median plus 2 SDs when we examined the distribution of LOS. To identify additional factors associated with serious influenza infection, we examined the association between prolonged hospitalization and various demographic and clinical characteristics. We performed a multivariate analysis using a logistic regression model to determine factors associated with prolonged LOS. Variables statistically significant at the .05 level on univariate analysis were included in the model. Effect modification between age and several chronic conditions was also considered. Unadjusted and adjusted ORs and corresponding 95% CIs were derived. All statistical calculations were performed by using SAS 9.1 (SAS Institute, Cary, NC) and Stata 8 (Stata Corp, College Station, TX). A 2-tailed P value of <.05 was considered significant for all statistical tests.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Estimated Incidence of Influenza-Related Hospitalization Among Children
Among a total of 745 case-patients identified with CA LCI, 231 (31%) resided in the neighborhood cohort. The demographic and clinical characteristics of children hospitalized with CA LCI from the neighborhood cohort were comparable to that of the entire study cohort with the following exceptions: hospitalized children in the neighborhood cohort were more likely to be black (90% vs 55%) or have asthma (31% vs 24%) (Table 2). However, the neighborhood case-patients were of similar race/ethnicity distribution as the overall neighborhood cohort. Information on asthma prevalence in the neighborhood cohort was not available for comparison.
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Most study subjects from the neighborhood (222 [96%] of 231) had either a chronic medical condition or were <5 years of age (data not shown), similar to the prevalence noted in the entire study cohort. On the basis of calculated 340540 child-years of observation, we estimated that the total incidence of influenza-related hospitalization in this cohort was 7 per 10000 child-years. To assess the impact of referral bias, we calculated the incidence of influenza-related hospitalization for a subgroup of children who lived in the 6 zip-code areas with
90% referral to the study hospital; the incidence of influenza-related hospitalization in this cohort was 8 per 10000 child-years (data not shown). We also calculated the age-specific incidence of hospitalization attributable to influenza in the 9–zip-code neighborhood cohort (Table 3). We found that children 0 to 23 months of age had the highest risk of hospitalization attributable to influenza (41.6 per 10000 child-years). Among premature infants, the incidence of influenza-related hospitalization was 19 per 10000 child-years (data not shown).
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Characteristics of Children Hospitalized With CA LCI
Over the 4-year study period we identified 826 patients who experienced 842 hospitalizations with LCI. Seventy patients with health care-associated LCI were excluded from all subsequent analyses. We excluded 8 patients who were >21 years of age from this analysis. Thirteen patients had > 1 hospitalization attributable to CA LCI; only the first hospitalization for each patient was included in this analysis (n = 745). Overall, 591 (79%) of the study subjects were infected with influenza A; the annual proportion of infections attributable to influenza A ranged from 33% to 98% (data not shown). Greater than 60% of children hospitalized with CA LCI were <24 months of age, and 18% were 2 to 4 years of age (Fig 1). Influenza virus infection was confirmed by SPIA (n = 529), DFA (n = 100), and viral culture (n = 104). Two patients underwent diagnostic testing at an outside hospital before admission to the study hospital, and the type of diagnostic assay used was unknown.
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The majority of children <2 years old (298 [68%] of 438), and many were 2 to 4 years of age (53 [39%] of 135) were previously healthy. Approximately half of the children (49%) hospitalized with CA LCI had an ACIP-recognized high-risk medical condition, including asthma (24%), NNMD (12%), immunosuppression (8%), and cardiac condition (7%) (Table 2). We identified 106 children (14%) with
2 medical high-risk conditions. Children with 1 medical high-risk conditions were older than otherwise healthy children hospitalized with CA LCI (median age: 3.1 vs 0.7 years; P < .001).
Hospital Course and Influenza-Related Complications
Five children died while hospitalized for CA LCI, including 2 children with congenital cardiac disease, 1 previously healthy child who was 14 months old, 1 patient with static encephalopathy attributable to severe birth trauma, and a 4-month-old former premature infant without active medical issues. There was no influenza season predominance in the distribution of these deaths. Among previously healthy children who required hospitalization for CA LCI, the case fatality rate was 2 per 382 (5.2 per 1000).
A total of 186 children experienced 1 influenza-related complication (Table 4). The incidence of influenza-related complications was higher among children who had a preexisting high-risk condition than for previously healthy children (29% vs 21%; OR: 1.6; 95% confidence interval [CI] 1.1–2.2). Among healthy children, infants <6 months had the lowest rate of complications (8%). The rates of complications in healthy children in other age groups were not statistically different: 6 to 23 months, 25%; 2 to 4 years, 40%; 5 to 11 years, 37%; 12 to17 years, 44%, and >17 years, 33%.
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Overall, suspected bacterial pneumonia was the most frequent complication and occurred in 110 children (15%). Children with high-risk medical conditions were more likely than healthy children to require intensive care (OR: 1.6; 95% CI: 1.2–2.5) or develop respiratory failure (OR: 2.8; 95% CI: 1.3–6.1). However, 56 children (15%) who lacked a high-risk medical condition were admitted to an ICU. During this 4-year study period, no child was diagnosed with influenza-related cardiomyopathy.
Predictors of Prolonged Length of Hospital Stay
The median duration of hospitalization for CA LCI was 2 days (interquartile range: 1–4 days), and 12% of our study population was hospitalized for >6 days, which was defined as prolonged LOS. On univariate analysis, there was no association between prolonged LOS and race/ethnicity, season, or influenza type. We performed multivariate analysis to identify independent factors associated with prolonged LOS. After adjusting for age, we found that specific preexisting conditions were independently associated with prolonged LOS, including cardiac disease (OR: 3.6; 95% CI: 1.8–7.1) and NNMD (OR: 5.7; 95% CI: 3.3–9.7).
Figure 2 illustrates the predicted probability of prolonged LOS for the variables in our final multivariate model: age, cardiac disease, and NNMD. Nonpremature infants 0 to 5 months old without cardiac disease or NNMD who were hospitalized with CA LCI had a 4% probability of a prolonged hospitalization. In contrast, premature infants 0 to 5 months old without cardiac disease or NNMD had a 22% probability of a prolonged hospitalization. The probability of a prolonged hospitalization was 8% for patients either 6 months to 4 years or 5 years of age. Patients with cardiac disease or those with a NNMD had an increased probability of a prolonged LOS (23% and 33%, respectively). Patients with both cardiac disease and a NNMD had a markedly increased probability of a prolonged LOS to 68%, regardless of the age of the child (Fig 2).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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In this report, we describe the largest US cohort study of children hospitalized with CA LCI and provide important new clinical and epidemiologic information about children hospitalized with influenza. First, we found that 7 of 10000 inner-city children <18 years of age were hospitalized each year attributable influenza in this cohort, and many of these children, particularly those <5 years of age, were otherwise healthy. This study also provides strong supporting evidence for the prevention of influenza among children with NNMD, a group newly recommended to receive annual influenza vaccination.7 Finally, we identified groups of chronically ill children at highest risk of prolonged hospitalization attributable to influenza, in particular, children with NNMD and cardiac disease.
Our data provide additional estimates of the incidence of influenza-related hospitalizations. By analyzing a subset of our study population who resided within an urban neighborhood cohort, we found that the incidence of hospitalization with laboratory-confirmed influenza for children <18 years of age was 7 per 10000 child-years. This estimate is similar to that calculated by Neuzil and others14–17 and provides support for previous analyses that relied on large administrative data sets to calculate the rates of influenza-attributable hospitalizations. In a prospective multisite study of laboratory-confirmed infections, the CDC-supported New Vaccine Surveillance Network estimated the influenza-hospitalization rate to be 9.0 per 10000 children for children <5 years of age.17 They also noted that children of black race/ethnicity or with chronic underlying illnesses had higher rates of influenza hospitalization. Surveillance for laboratory-confirmed influenza-associated hospitalizations in children was performed by the CDC-supported Emerging Infections Program, which noted an overall incidence of 3.6 per 10000 children.18 Rates of hospitalization found in our study might be somewhat higher than those observed by the Emerging Infections Program because of differences in use of viral diagnostic testing. In addition, we hypothesize that a higher prevalence of certain chronic medical conditions in our neighborhood cohort than in the general population might have led to increased rates of hospitalization for children in our inner-city cohort. For example, asthma and sickle cell disease are 2 diseases that are associated with influenza complications and were more prevalent in this population. In addition, over three quarters of the children residing in our neighborhood cohort were black, a racial group that has been previously found to be at higher risk of pediatric influenza-related hospitalizations compared with white children.16 Interestingly, 90% of hospitalized children from our neighborhood cohort were black although data from the 2000 US Census estimated that 77% of children living in this geographic area were black. We have identified several possible reasons for the apparent excess rate of hospitalization among black children in our neighborhood cohort. First, the prevalences of diseases such as hemoglobinopathies and asthma are higher among black than nonblack children and are likely to have contributed to an increased rate of hospitalization among the black children in our cohort. The proportion of children from this community who were immunized against influenza might vary on the basis of race as has been noted by other investigators.19 In addition, misclassification bias might have contributed to the apparent racial discrepancy in influenza hospitalizations. Although racial data from both hospital administrative data sets and the US Census are self-reported, different categories of race are used. For example, the 2000 US Census offered respondents to report "two or more races" but the hospital admission form did not. Finally, differential referral might have led black children to be admitted to the study hospital more frequently than nonblack children. Future population-based studies are needed to examine the association between race and need for influenza hospitalization.
We found that one quarter of all pediatric hospitalizations attributable to influenza occurred in infants <6 months of age, a group for whom neither influenza vaccines nor antiviral medications are currently licensed. Other investigators also noted that influenza leads to a substantial burden of disease among young infants.16,20–23 Current recommendations to prevent influenza infection of young infants include vaccination of pregnant women, members of households that include young infants, and childcare providers.7 However, recent data suggest that these groups of individuals often do not receive influenza vaccine as recommended.24 Given the substantial burden of disease among young infants, more aggressive campaigns to vaccinate healthy individuals who surround these children are needed. In addition, future studies of active immunization of young infants will address these issues.
We found that many of the previously healthy children hospitalized with influenza were 2 to 4 years of age and that the rate of hospitalization among preschool-aged children was second only to that of children <2 years of age. These findings support the recent recommendation by the ACIP that children 2 to 4 years of age should receive influenza vaccination each year.25 We observed a higher rate of hospitalization among children of this age group than previously estimated by Izurieta and colleagues.15 In a study of children enrolled in 2 large managed care organizations, these investigators calculated the rate of excess hospitalizations attributable to influenza to be 1.8 to 4.4 per 10000 child-years. The lower rates observed in these studies might be related to difficulties estimating the rate of influenza hospitalizations during periods when other respiratory viruses are circulating, differences in the race/ethnicity or economic background of the populations of the study populations, or differences in the regional burden of disease during the seasons of study.
We observed a relatively high rate of complications among children hospitalized with influenza. Pneumonia was the most common complication and occurred in 15% of hospitalized children. Although high-risk children were at greater risk of developing an influenza-related complication, 1 in 5 previously healthy children also experienced an influenza-related complication. These findings provide additional support for the vaccination of healthy children.
Most children hospitalized with influenza had a short hospital stay with a median LOS of 2 days; however, 15% of high-risk children and 7% of other children were hospitalized for >6 days. Prolonged hospital stay was significantly associated with cardiac disease or NNMD. The presence of both disease categories further increased the likelihood of prolonged hospitalization. This study confirmed the findings of other recent studies regarding NNMD as a risk factor for serious influenza infection11,26,27 and supports the addition of this group of chronically ill children to other populations recommended to receive annual influenza vaccination. These data can guide clinicians and public health officials on the optimal use of vaccine during times of vaccine shortage. In addition, health care organizations that provide care to chronically ill children might use this knowledge to enhance vaccination rates among their patients at highest risk of prolonged hospitalization.
We recognize several limitations of this study. First, ascertainment bias might have reduced the number of mild or atypical cases of influenza detected among children admitted to our hospital. Although a highly sensitive algorithm for the detection of influenza infection is routinely used to diagnose children hospitalized with respiratory symptoms during the winter, it is possible that patients with minimal respiratory symptoms might not have undergone diagnostic testing for influenza. In addition, it is possible that either false-positive or false-negative viral assay determinations might have contributed to ascertainment bias. However, we believe our algorithm is highly specific on the basis of the absence of positive determinations during months when influenza virus is not in circulation. The racial and economic composition of the population-based cohort from which we derived our estimated rates of influenza-associated hospitalization limits the ability to generalize these findings to other populations. Finally, we were unable to capture accurate influenza immunization data for the children in our cohort and thus could not assess how vaccination might have influenced the risk of prolonged hospitalization.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Most children hospitalized with influenza were in groups either currently recommended to receive influenza vaccination or were <6 months of age. In addition, the presence of NNMD, a condition recently added to the ACIP list of high-risk conditions in 2005, was found to be an important risk factor for prolonged hospitalization. Current efforts should be made to vaccinate eligible high-risk children and their close contacts. Additional data are needed to define the relative benefits of influenza vaccination of high-risk children as compared with healthy school-aged children and the benefit of vaccinating all children
6 months.
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ACKNOWLEDGMENTS |
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This work was supported by CDC grant H23/CCH32253-02.
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FOOTNOTES |
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Accepted Nov 14, 2006.
Address correspondence to Susan E. Coffin, MD, MPH, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail: coffin{at}email.chop.edu
Dr Rosenquist's current affiliation is Department of Pediatrics, Children's Hospital, Boston, MA.
Dr Herrera's current affiliation is Wyeth-Lederle, Inc, Madison, NJ.
The authors have indicated they have no financial relationships relevant to this article to disclose.
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L. Finelli, A. Fiore, R. Dhara, L. Brammer, D. K. Shay, L. Kamimoto, A. Fry, J. Hageman, R. Gorwitz, J. Bresee, et al. Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection Pediatrics, October 1, 2008; 122(4): 805 - 811. [Abstract] [Full Text] [PDF]
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Committee on Infectious Diseases Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008 Pediatrics, April 1, 2008; 121(4): e1016 - e1031. [Abstract] [Full Text] [PDF]
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