Published online June 22, 2007
PEDIATRICS Vol. 119 No. 3 March 2007, pp. e587-e595 (doi:10.1542/peds.2006-1878)
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ARTICLE

Vaccine Effectiveness Against Medically Attended, Laboratory-Confirmed Influenza Among Children Aged 6 to 59 Months, 2003–2004

Carrie M. Shuler, DVM, MPHa,b, Martha Iwamoto, MD, MPHa, Carolyn Buxton Bridges, MDc, Mona Marin, MDa, Ruth Neeman, RN, BSNb, Paul Gargiullo, PhDc, Terrace A. Yoder, MDd, Harry L. Keyserling, MDe and Pauline D. Terebuh, MD, MPHb

a Epidemic Intelligence Service
c Centers for Disease Control and Prevention, Atlanta, Georgia
b Notifiable Diseases Section, Division of Public Health, Georgia Department of Human Resources, Atlanta, Georgia
d Children’s Medical Group, Atlanta, Georgia
e School of Medicine, Emory University, Atlanta, Georgia


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. Influenza is a leading cause of illness among children. Studies rarely have measured influenza vaccine effectiveness among young children, particularly when antigenic match between vaccine and circulating viruses is suboptimal. We assessed vaccine effectiveness against medically attended, laboratory-confirmed influenza for children who were aged 6 to 59 months during the 2003–2004 influenza season.

METHODS. In a case-control study that was conducted in a single pediatric practice, case patients who were aged 6 to 59 months and had laboratory-confirmed influenza were age matched 1:2 to eligible control subjects. Vaccination status was ascertained as of the date of the case patient’s symptom onset. Conditional logistic regression was used to calculate vaccine effectiveness, adjusting for underlying medical conditions and health care usage.

RESULTS. We identified 290 influenza case patients who were seen for medical care from November 1, 2003, to January 31, 2004. Vaccine effectiveness among fully vaccinated children, compared with unvaccinated children, was 49%. Partially vaccinated children who were aged 6 to 23 months had no significant reduction in influenza (vaccine effectiveness: –70%), but partially vaccinated children who were aged 24 to 59 months had a significant (65%) reduction in influenza, compared with unvaccinated children.

CONCLUSIONS. Full vaccination provided measurable protection against laboratory-confirmed influenza among children who were aged 6 to 59 months during a season with suboptimal vaccine match. No vaccine effectiveness was identified with partial vaccination among children who were aged 6 to 23 months, affirming that children need to be fully vaccinated to obtain protective effects. These results strengthen the evidence of the vaccine’s ability to reduce substantially the burden of disease in this age group.

Key Words: influenza • children • vaccine effectiveness

Abbreviations: ACIP—Advisory Committee on Immunization Practices • VE—vaccine effectiveness • ILI—influenza-like illness • RAD—reactive airway disease • OR—odds ratio • aOR—adjusted odds ratio • CI—confidence interval • P&I—pneumonia and influenza

Influenza is one of a limited number of viral respiratory diseases that are preventable by vaccination. It is common among young children, resulting in an estimated annual average of 50 to 95 outpatient visits and 6 to 27 emergency department visits per 1000 children, 9 hospitalizations per 10000 children, and an annual average of ~92 deaths among US children aged <5 years.1–4 Compared with older children, children who are aged <24 months have higher rates of acute otitis media, pneumonia and other lower respiratory tract disease, and hospitalization related to the influenza infection.1,5–8

For maximization of the immune response and protection against influenza, previously unvaccinated children who are aged <9 years and for whom vaccine is recommended should receive 2 doses of influenza vaccine at least 1 month apart.9 The short period between vaccine availability and the start of the influenza season, however, can make receipt of 2 doses before influenza exposure difficult and requires extra health care provider visits.10–12

Limited data have been published on the effectiveness of influenza vaccine among young children overall and particularly on the effectiveness of 1 vs 2 doses.13–17 Such data are especially important during years of influenza vaccine shortage or when the influenza season occurs early, because children might not have received their second dose of vaccine before being exposed.

For the 2003–2004 influenza season, the Advisory Committee on Immunization Practices (ACIP) encouraged vaccinating all children who are aged 6 to 23 months and household contacts of children aged <2 years and continued to strongly recommend the vaccination of children who are aged ≥6 months with medical conditions that place them at increased risk for influenza-related complications.18 In 2004, ACIP recommended annual vaccination for all children who are aged 6 to 23 months.19

Nationally, during the 2003–2004 influenza season, influenza viruses began circulating unusually early and influenza A (H3N2) viruses predominated.20 In Georgia, the first reported laboratory-confirmed patient had illness onset in October, and overall influenza activity peaked in late December.21 Only 25% of the circulating influenza viruses nationally and in Georgia were similar antigenically to the vaccine strain, and severe complications, including pediatric deaths, were reported.20,22 Because clinical illness that is caused by influenza virus is not distinguishable from other causes of respiratory illness, laboratory confirmation of influenza is essential to increase the accuracy of vaccine effectiveness (VE) estimates. Use of nonspecific outcomes for influenza diagnoses may lower VE estimates substantially.23 We evaluated the effectiveness of the trivalent inactivated influenza vaccine against medically attended, laboratory-confirmed influenza among children who were aged 6 to 59 months in Georgia during a season with a suboptimal antigenic match between the vaccine and circulating strains.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Population and Location
Children who were examined for 1 or more outpatient visits (either well-child or sick visits) at a private metropolitan Atlanta pediatric practice during February 1, 2003, to January 31, 2004, and who were born during October 1, 1998, to April 1, 2003 (ie, aged 6–59 months during the 2003–2004 influenza season), were eligible for the study. We identified 7139 children who met the inclusion criteria (study children). The study practice has 16 health care providers and serves ~400 patients a day. The physicians offered influenza vaccine to patients consistent with the 2003–2004 ACIP guidelines (children aged ≥6 months at high-risk, all children aged 6–23 months, and household contacts of children aged <2 years) and routinely performed in-house rapid influenza antigen testing on children with influenza-like illness (ILI). This assessment of influenza VE was initiated as a public health response; therefore, the Centers for Disease Control and Prevention and the Georgia Division of Public Health determined these activities as nonresearch and did not require review by an institutional review board. However, personal identifiers were removed and confidentiality was preserved in data collection and analysis.

Laboratory-Confirmed Influenza Outcome
The practice providers used the QuickVue Influenza test (Quidel Corp, San Diego, CA) to screen nasopharyngeal swab samples for influenza antigen. This rapid antigen test has a sensitivity of ~73% and specificity of ~96%.24 Because of a test kit shortage in the community, additional kits were provided to the practice on January 5, 2004, to allow for influenza testing at the practice without interruption. To determine the feasibility of conducting the retrospective observational study at the pediatric practice, a survey of the providers was conducted to evaluate potential diagnostic testing biases. The providers were asked how their patients’ vaccination status, age, underlying medical conditions, clinical symptoms, and insurance reimbursement affected their decision to test for influenza (more likely to test, less likely to test, or would not affect decision to test).

Case Patient Identification
Case patients were identified as those with laboratory-confirmed influenza during November 1, 2003, to January 31, 2004. We conducted case finding through review of the study practice’s laboratory logbooks. Case patient medical charts were reviewed by using a chart-abstraction tool. Chart abstractors were not blinded to the patient’s case status. Information was collected on illness symptoms, treatment with influenza antiviral medication, influenza complications, influenza vaccination, gender, chronic medical conditions, and child care or school participation.

Control Subject Selection
Two age-matched study children were randomly selected as control subjects for each case patient. The eligible control subjects for each case patient included study children who were born during the same month and year and had not become a case before the influenza illness onset date of the case patient. We excluded from the study non-Georgia residents and children with no vaccination history indicated in the medical chart. Case patients were eligible to serve as control subjects until the date of chart-documented, laboratory-confirmed influenza.25,26 Although limited in-and-out migration from the study population probably occurred, any child with a visit to the practice during the previous year was considered at risk during the influenza season and became unavailable for control section only on the date of becoming a case patient and thereafter.27 We did not exclude children who were examined at the practice with ILI, who were not tested for influenza. Selecting a child as a control subject more than once for case patients with different symptom onset dates did not necessarily lead to repeat exposure information, because vaccination status varied with time. The vaccination status of each set of case patients and control subjects was compared on the date of illness onset of the case patient.

Vaccination Status
By using the date of symptom onset as the anchor date, vaccination status and other covariates for case patients and their age-matched control subjects were categorized. We considered children who had received 2 doses of influenza vaccine at least 1 month apart and ≥14 days before the anchor date as fully vaccinated. Children who were vaccinated during a previous season needed only 1 dose of vaccine during the 2003–2004 season ≥14 days before the anchor date to be fully vaccinated. We categorized children with the following 2 situations as partially vaccinated: (1) children who were not vaccinated in a previous season and had received 2 doses of influenza vaccine since September 2003 with an anchor date <14 days after the second dose and (2) children who were not vaccinated in a previous season and received only 1 dose of vaccine since September 2003 ≥14 days before the anchor date. We considered children who had received no doses of influenza vaccine during the 2003–2004 season on or before the anchor date and children who had received 1 dose since September 2003 <14 days before the anchor date as unvaccinated, even if they had received vaccine during a previous season.

Presence of Underlying Medical Conditions
ACIP recommendations for multiple years have targeted children with certain medical conditions to be at increased risk for complications related to influenza virus infection.5,9 We sought documentation of high-risk conditions in the medical chart and included conditions that were designated by the ACIP during the 2003–2004 season: reactive airway disease (RAD) or asthma (listed explicitly on at least 2 occasions), chronic lung disease, chronic metabolic disease, cardiovascular disease, renal disease, hemoglobinopathy, cancer, other immunosuppressive conditions, long-term aspirin therapy, or residence in a long-term care facility.18

Child Care or School Status
We ascertained child care or school participation to adjust for the possible increase in influenza virus exposure; priming from previous influenza infections has been reported to be associated with higher immune response after vaccination.12,16,28–30 The practice physicians collected on a standardized form information on child care or school attendance during health care visits. When no notation had been made in the medical chart during our study period or the section on the medical chart had been left blank, we recorded the child’s out-of-home care status as unknown.

Health Care Usage
We used the number of office visits billed for each child during the year before the beginning of the 2003–2004 influenza season (November 1, 2002, to November 1, 2003) as an indicator of health care usage. When the number of visits was more than the median value for the child’s corresponding age category, the child was classified as a high health care user.

Statistical Analysis
We modeled the association between influenza vaccination and medically attended, laboratory-confirmed influenza with conditional logistic regression. A matched analysis was used to estimate an odds ratio (OR) for disease in which each matched set (1 case patient and 2 control subjects) was treated as a unique stratum. We included high-risk status and health care usage in the final models.31 We analyzed vaccination status as a categorical exposure measure with unvaccinated as referent. Fully vaccinated children were compared with unvaccinated children. Partially vaccinated children were compared with unvaccinated children who might have become partially vaccinated during the 2003–2004 influenza season (ie, children who were categorized as unvaccinated and were not vaccinated during a previous season). We also calculated separate VE estimates for children who were aged 6 to 23 months and 24 to 59 months. The adjusted OR (aOR) was used to estimate VE by using the formula VE = (1 – aOR) x 100.13,23


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Provider Testing Practices
Of the 16 providers, 8 completed the survey. One provider reported that patients’ vaccination status affected the decision to test for influenza (more likely to test unvaccinated patients and less likely to test vaccinated patients). The other respondents reported that patients’ vaccination status did not affect their decision to test. Many of the 8 practitioner-respondents identified other clinical factors that would make them more likely to test a patient for influenza: patient high-risk condition (n = 7), household contact at increased risk for an influenza-related complication (n = 8), fever >104°F (n = 6), illness duration <2 days (n = 4), and decision to prescribe antiviral medications (n = 8). A fever <101°F was identified by 5 respondents as a patient factor that would make them less likely to test.

Description of Case Patients
A total of 293 children who were aged 6 to 59 months and had laboratory-confirmed influenza during November 1 to January 31, 2004, were identified from the practice’s records. Three children did not have complete vaccination records and were excluded from the analysis (N = 290; Fig 1). The majority of case patients who were identified early in the season were unvaccinated. The epidemiologic curve of case patients who were identified in the practice was similar to the curve that was identified through Georgia’s influenza surveillance.


Figure 1
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  		FIGURE 1 Laboratory-confirmed influenza cases (n = 290) according to date of influenza onset and vaccination status in the Georgia pediatric practice, 2003–2004.

 
The case patients’ clinical course and treatment are described in Table 1 by age category (6–23 months and 24–59 months). Fever, cough, and rhinorrhea were listed as symptoms for 97%, 89%, and 83% of all case patients, respectively. The physicians prescribed oseltamivir for 133 (46%) of the influenza case patients, and 1 patient was prescribed amantadine. Influenza-related complications were identified within 3 weeks of their influenza illness onset among 32% of children who were aged 6 to 23 months and 22% of children who were aged 24 to 59 months (Table 1). Only 2 children were hospitalized as a result of their influenza infection: a child who was aged 16 months and had a history of RAD/asthma and a child who was aged 9 months and was not at high risk. Both children were fully vaccinated for influenza at the time of illness onset.


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  		TABLE 1 Symptoms, Treatment, and Complications of Influenza Case Patients (N = 290) According to Age Category

 
A comparison of influenza case patient symptoms before and after the receipt of supplemental test kits to the practice found that children who were aged 6 to 23 months and tested positive for influenza were less likely to present with a cough, and children who were aged 24 to 59 months were less likely to present with vomiting after the test kits were provided compared with before. Otherwise, there was no difference in the presenting symptoms of influenza-positive patients before and after the test kits were provided to the practice.

Characteristics of Case Patients and Age-Matched Control Subjects
Table 2 describes the vaccination status, gender, medical conditions, child care participation, and health care usage of the case patients and their age-matched control subjects. A higher proportion of children who were aged 6 to 23 months (42.7% of the case patients and 56.8% of control subjects) compared with older children were considered fully vaccinated at the time of their respective anchor dates. Among children who were aged 24 to 59 months, 22.3% of case patients and 30.5% of control subjects were fully vaccinated. Gender was evenly distributed between the age categories and between the case patients and control subjects.


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  		TABLE 2 Characteristics of Influenza Case Patients and Age-Matched Control Subjects According to Age Category (N = 870)

 
RAD/asthma was the most prevalent underlying medical condition, with 19.8% of case patients and 14.9% of control patients who were aged 6 to 23 months having documentation in the medical chart during the study period; among children who were aged 24 to 59 months, 18.4% of case patients and 17.9% of control subjects had RAD or asthma. A total of 52.5% of case patients and 39.2% of control subjects who were aged 6 to 23 months participated in child care or school, compared with 77.7% of case patients and 74.9% of control subjects who were aged 24 to 59 months. Younger children had higher health care usage rates than older children, with a median of 11 office visits for case patients and 9 visits for control subjects during the year before the 2003–2004 influenza season. The overall 6- to 23-month age category median number of office visits was 10. Case patients who were aged 24 to 59 months had a median of 5 office visits, and control subjects had a median of 4 visits, with an overall age category median number of 4 office visits.

VE Estimates
Vaccination status, health care usage, and child care participation were associated significantly with influenza in the univariate model. However, in the multivariate model, only vaccination status and health care usage were associated independently with laboratory-confirmed influenza. VE estimates were adjusted for health care usage, an important confounder, and high-risk status for comparability with previously reported VE estimates (Table 3). In the multivariate model, child care status did not affect the relationship between vaccination and having influenza and was not included in the final model. For children who were aged 6 to 59 months, fully vaccinated children had a significant reduction in influenza when compared with unvaccinated children, with a VE estimate of 49% (95% confidence interval [CI]: 30%–60%). Partially vaccinated children who were aged 6 to 59 months did not have a significant reduction in influenza (aOR: 0.76; 95% CI: 0.5–1.2).


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  		TABLE 3 Multivariate Conditional Logistic Regression Analysis of Laboratory-Confirmed Influenza by Vaccination Status, Adjusting for High-Risk Status and Health Care Usage According to Age Category (N = 870)

 
Fully vaccinated children who were aged 6 to 23 months had a significant (52%) reduction in influenza, compared with unvaccinated children (95% CI: 20%–70%). Children who were aged 6 to 23 months and were partially vaccinated did not have a significant reduction in influenza, compared with unvaccinated children who were not vaccinated in a previous season (aOR: 1.70; 95% CI: 0.9–3.8). A significant (45%) reduction in influenza for children who were aged 24 to 59 months was identified when fully vaccinated children were compared with unvaccinated children (95% CI: 10%–70%). Partially vaccinated children who were aged 24 to 59 months had a significant (65%) reduction in influenza when compared with unvaccinated children who had not been vaccinated during a previous season (95% CI: 30%–80%).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Fully vaccinated children who were aged 6 to 59 months and partially vaccinated children who were aged 24 to 59 months had significant reductions in medically attended, laboratory-confirmed influenza, compared with respective unvaccinated children, even during a year with a suboptimal match between the vaccine and circulating strains. However, we identified no VE with partial vaccination among children who were aged 6 to 23 months. These results support recommendations for annual influenza vaccination of children and highlight the importance of achieving full vaccination before the start of the influenza season.

Comparison With Other Studies
Our results are consistent with other studies that have evaluated either the efficacy or the effectiveness of the influenza vaccine among children through randomized, controlled trials (efficacy) and observational studies (effectiveness).12–15,17 VE estimates can vary widely, depending on the study population (age, immune health, previous exposure to influenza, and access to vaccine), specificity of the outcome (laboratory-confirmed influenza through serology, culture, or rapid antigen tests or such symptoms as ILI), and the influenza season (how the vaccine strains relate to the circulating strains and relative contribution of influenza to the burden of ILI).

In a study by Ritzwoller et al13 during the 2003–2004 influenza season, VE against ILI (not laboratory confirmed) for fully vaccinated children who were aged 6 months to 8 years was 23% and 51% for pneumonia and influenza (P&I). For fully vaccinated children who were aged 6 to 23 months, VE was 25% against ILI and 49% against P&I.13 VE against P&I yielded a similar VE to the laboratory-confirmed influenza outcome in our study. Unlike the study by Ritzwoller et al, our study identified a protective effect for partial vaccination among children who were aged 24 to 59 months. This difference might be caused by our population’s having had more previous exposures to influenza, or the more specific outcome of laboratory-confirmed influenza allowed for the detection of this benefit. Similar to Ritzwoller et al, our study provides reassurance that vaccination of young children provides benefit, even in a year with a suboptimal match.

A limited number of studies have been published on the effectiveness or efficacy of the influenza vaccine among children aged who are <5 years.13–15,17,28,32 In a Cochrane review of studies that were conducted among healthy children, published in early 2005, only 1 study of children who were aged ≤2 years by Hoberman et al14 was included. In that 2-year randomized, placebo-controlled study, vaccine efficacy against culture-confirmed influenza was 66% during a year when the attack rate was 16% among unvaccinated children and –7% during a second year, when only 3% of children had influenza. A limited number of children during the second-year study cohort were influenza culture positive, substantially reducing the ability to detect a difference between the vaccine groups. The decreased sensitivity and specificity of the rapid antigen test that was used in our study compared with culture and the less optimal antigenic match between the vaccine and circulating strains might explain the lower VE that was identified during our study.

Our study was unique in that the study population was highly vaccinated: 77% of study participants who were aged 6 to 23 months had ≥1 dose of influenza vaccine by the end of the season. In Georgia overall, only 19.5% (95% CI: 12.9–28.4) of children who were aged 6 to 23 months during the 2003–2004 influenza season had had ≥1 dose of influenza vaccine.33 Providers at the pediatric practice routinely tested patients with suspect illness for influenza. For young children who might experience numerous medically attended respiratory illnesses during the first years of life, our main outcome measure of medically attended, laboratory-confirmed influenza rather than ILI is a substantial advantage in providing an influenza-specific VE estimate. In addition, chart and billing record review of all case patients and control subjects permitted precise ascertainment of influenza vaccination dates, underlying medical conditions, health care usage, and child care or school attendance. These factors can influence a patient’s vaccination status (opportunity or health indication for vaccination) and also are related to diagnosis of laboratory-confirmed influenza. Adjusting for these variables allowed us to control for their potentially confounding effect in our assessment of influenza VE.31,34

Partially Vaccinated Children
We found a significant reduction in laboratory-confirmed influenza among partially vaccinated children who were aged 24 to 59 months. The VE estimate for partially vaccinated children who were aged 24 to 59 months was higher than that for fully vaccinated children, but the sample sizes were small and the CIs for the 2 estimates overlapped. Older children are less likely to be immunologically naïve and therefore can produce a protective response with a single dose of influenza vaccine.28 However, given the yearly variability in the circulation of influenza viruses from community to community, many children who are aged 24 months to 8 years are likely not to have been exposed to circulating influenza viruses.28,35 Therefore, previously unvaccinated children who are aged <9 years should continue to be provided 2 doses to offer maximum protection from circulating types and subtypes of influenza.

Limitations
Observational VE studies similar to our study have intrinsic limitations.23 Bias in selection of patients for vaccination or in the diagnosis of influenza cannot be excluded because of variability in patient health care–seeking behaviors. Providers were aware of the vaccination status of the children when deciding which patients to test for influenza. Preferentially vaccinating patients with an increased risk for exposure to influenza (eg, children who were enrolled in child care) might decrease the VE estimate, whereas preferentially testing unvaccinated patients might increase the VE estimate. We attempted to minimize these potentially confounding effects by evaluating the contribution of high-risk status and child care participation, by controlling for health care usage, and by choosing a pediatric practice study site that strongly supported the ACIP vaccination recommendations and routinely tested patients who had ILI for influenza. The provider survey indicated that most of the practitioners were not influenced by vaccination status when deciding to test for influenza; however, a standardized protocol for influenza testing did not exist, and testing was at the discretion of individual providers.

Although using influenza rapid testing for laboratory confirmation of medically attended influenza enhanced the precision of the influenza outcome measure, misclassification of case patients and control subjects still was possible. Patients with mild or atypical influenza symptoms might not have been tested for influenza, although we have no reason to believe that symptoms differed among vaccinated compared with unvaccinated children with influenza. Virus shedding is greatest during the first days of influenza infection; therefore, patients who were tested during the early phase of the illness were more likely to test positive. Because the influenza rapid test is ~73% sensitive, certain medically attended cases of influenza might not have been detected. With a rapid test specificity of 96%, certain patients might have falsely tested positive. Overall, the potential to misclassify case patients as control subjects was greater and might have decreased the VE estimate. Because the study population became more vaccinated as the season progressed and additional rapid test kits were made available to the practice, the impact of detecting milder cases later in the season on VE estimates is difficult to predict. It is unlikely to have been profound, because individual providers had established approaches to evaluating ILI and testing for influenza. Overall, most factors that could affect the VE estimate would result in an underestimation of the vaccine’s true effectiveness.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Influenza vaccination provided protection against medically attended, laboratory-confirmed influenza among children who were aged 6 to 23 months and 24 to 59 months during a season with a suboptimal match between vaccine and circulating strains. The benefit of the vaccine was measurable among children who were fully vaccinated in comparison with those who were unvaccinated and resulted in an estimated decreased risk for medically attended influenza of 52% and 45%, respectively. Older children, those who were aged 24 to 59 months, benefited from partial vaccination (≥14 days since receipt of 1 of 2 recommended doses), but we determined no VE with partial vaccination among younger children. These results support recommendations for influenza vaccination of children and strengthen the evidence of the vaccine’s ability to reduce substantially the burden of disease among this age group.


   ACKNOWLEDGMENTS
 
We thank Jim Alexander, Sharon Bloom, and Jane Seward for guidance with study design and data interpretation; Connie Knight for administrative support; and Erin Murray and Mona Heaven for assistance with statistical and data management.


   FOOTNOTES
 
Accepted Sep 26, 2006.

Address correspondence to Carrie M. Shuler, DVM, MPH, Georgia Division of Public Health, 2 Peachtree St, Suite 14-232, Atlanta, GA 30303. E-mail: cmshuler{at}dhr.state.ga.us

The authors have indicated they have no financial relationships relevant to this article to disclose.

This work was presented in part at the Infectious Diseases Society of America Conference; October 6–9, 2005; San Francisco, CA.

The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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