Katherine A. Poehling

The burden of respiratory syncytial virus infection in young children.

BACKGROUND The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. METHODS We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. RESULTS Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. CONCLUSIONS RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection.

National Impact of Universal Childhood Immunization With Pneumococcal Conjugate Vaccine on Outpatient Medical Care Visits in the United States

BACKGROUND. Since introduction of the heptavalent pneumococcal conjugate vaccine in the United States in 2000, rates of invasive pneumococcal disease have declined. However, the national impact of heptavalent pneumococcal conjugate vaccine on pneumonia and otitis media remains unknown. OBJECTIVES. We compared national rates of outpatient visits for pneumonia and otitis media in children before and after heptavalent pneumococcal conjugate vaccine introduction. METHODS. Rates of ambulatory visits for pneumococcal and nonspecific pneumonia, otitis media, and other acute respiratory infections were compared before (1994–1999) and after (2002–2003) heptavalent pneumococcal conjugate vaccine introduction using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. To evaluate vaccine effects while accounting for temporal variability, ratios of pneumococcal-related disease rates in children <2 years old (vaccine target population) and in children 3 to 6 years old (not routinely vaccinated) were evaluated using a Poisson regression analysis. For children <2 years old, the differences between observed and expected rates were the estimated vaccine effects. RESULTS. After the introduction of heptavalent pneumococcal conjugate vaccine, otitis media visit rates declined by 20% in children aged <2 years. This decline represented 246 fewer otitis media visits per 1000 children aged <2 years annually. There were no significant decreases in outpatient visit rates for pneumonia or other acute respiratory infections for children aged <2 years. CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, national rates of otitis media visits declined significantly in children <2 years old. Persistence of this trend will produce a significant reduction of the otitis media burden and further enhance the cost-effectiveness of heptavalent pneumococcal conjugate vaccine.

Respiratory Syncytial Virus–Associated Hospitalizations Among Children Less Than 24 Months of Age

BACKGROUND: Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. However, estimates of the RSV hospitalization burden have varied, and precision has been limited by the use of age strata grouped in blocks of 6 to ≥12 months. METHODS: We analyzed data from a 5-year, prospective, population-based surveillance for young children who were hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain reaction) RSV acute respiratory illness (ARI) during October through March 2000–2005. The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates. RESULTS: There were 559 (26%) RSV-infected children among the 2149 enrolled children hospitalized with ARI (85% of all eligible children with ARI). The average RSV hospitalization rate was 5.2 per 1000 children <24 months old. The highest age-specific rate was in infants 1 month old (25.9 per 1000 children). Infants ≤2 months of age, who comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9 per 1000 children. Most children (79%) were previously healthy. Very preterm infants (<30 weeks’ gestation) accounted for only 3% of RSV cases but had RSV hospitalization rates 3 times that of term infants. CONCLUSIONS: Young infants, especially those who were 1 month old, were at greatest risk of RSV hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy. To substantially reduce the burden of RSV hospitalizations, effective general preventive strategies will be required for all young infants, not just those with risk factors.

Impact of maternal immunization on influenza hospitalizations in infants

We sought to determine whether maternal vaccination during pregnancy was associated with a reduced risk of laboratory-confirmed influenza hospitalizations in infants <6 months old. Active population-based, laboratory-confirmed influenza surveillance was conducted in children hospitalized with fever and/or respiratory symptoms in 3 US counties from November through April during the 2002 through 2009 influenza seasons. The exposure, influenza vaccination during pregnancy, and the outcome, positive/negative influenza testing among their hospitalized infants, were compared using logistic regression analyses. Among 1510 hospitalized infants <6 months old, 151 (10%) had laboratory-confirmed influenza and 294 (19%) mothers reported receiving influenza vaccine during pregnancy. Eighteen (12%) mothers of influenza-positive infants and 276 (20%) mothers of influenza-negative infants were vaccinated (unadjusted odds ratio, 0.53; 95% confidence interval, 0.32-0.88 and adjusted odds ratio, 0.52; 95% confidence interval, 0.30-0.91). Infants of vaccinated mothers were 45-48% less likely to have influenza hospitalizations than infants of unvaccinated mothers. Our results support the current influenza vaccination recommendation for pregnant women.

Accuracy and interpretation of rapid influenza tests in children.

BACKGROUND. Influenza rapid antigen detection (rapid tests) can provide timely identification of infection and aid in clinical decision-making. Although the interpretation of test results depends on test characteristics and influenza prevalence, this information is limited in routine clinical practice. OBJECTIVE. We sought to assess the times at which rapid tests are most predictive of influenza infection. METHODS. The New Vaccine Surveillance Network enrolled children aged <5 years who were hospitalized with respiratory symptoms or fever from October 2000 through September 2004. Nasal and throat swabs were obtained, and influenza virus was detected by culture and reverse-transcription polymerase chain reaction. Provider-ordered rapid influenza tests were compared with the criterion standard (culture and reverse-transcription polymerase chain reaction) to determine their sensitivity and specificity. The New Vaccine Surveillance Network also enrolled children in outpatient settings during the 2002–2003 and 2003–2004 influenza seasons and determined the weekly influenza prevalence among symptomatic children. Trends in weekly predictive values of the rapid tests were estimated over the influenza seasons. RESULTS. Rapid influenza tests had an overall sensitivity of 63% and specificity of 97%. In 2002–2003, the prevalence of influenza in symptomatic outpatient children peaked at 21% and stayed above 10% for ∼4 weeks. In contrast, in 2003–2004, influenza prevalence peaked at 60% and remained above 20% for ∼6 weeks. The positive predictive value of the rapid tests approached 80% when influenza prevalence was ≥15% but decreased to <70% when influenza prevalence was <10%. CONCLUSIONS. Influenza prevalence varies between and within seasons. On the basis of our estimates, rapid tests are of limited use when prevalence is <10%. The appropriate interpretation of rapid influenza tests requires local influenza surveillance and timely communication of this information to the practitioners.

Influenza Burden for Children With Asthma

OBJECTIVE. The goal was to estimate the influenza disease burden among children with asthma and among healthy children by using active, laboratory-confirmed, population-based surveillance. METHODS. Children 6 to 59 months of age residing in 3 US counties who were hospitalized with acute respiratory illnesses or fever were enrolled prospectively from 2000 through 2004. Similar children who presented to clinics and emergency departments during 2 of the influenza seasons (2002–2004) were enrolled. Rates of influenza-attributable outpatient visits and hospitalizations for children with asthma and for healthy children were estimated. History of asthma and receipt of influenza vaccine for the study children were determined through parental report. The prevalence of asthma in the surveillance population was assumed to be 6.2% for children 6 to 23 months of age and 12.3% for children 24 to 59 months of age. RESULTS. Of 81 children 6 to 59 months of age with influenza-confirmed hospitalizations in 2000 to 2004, 19 (23%) had asthma. Average annual influenza-attributable hospitalization rates were significantly higher among children with asthma than among healthy children 6 to 23 months of age (2.8 vs 0.6 cases per 1000 children) but not children 24 to 59 months of age (0.6 vs 0.2 case per 1000 children). Of 249 children 6 to 59 months of age with influenza-confirmed outpatient visits in 2002 to 2004, 38 (15%) had asthma. Estimated outpatient influenza-attributable visit rates were higher among children with asthma than among healthy children 6 to 23 months of age (316 vs 152 cases per 1000 children) and 24 to 59 months of age (188 vs 102 cases per 1000 children) in 2003 to 2004. Few parents reported that their children had been vaccinated, including <30% of children with asthma. CONCLUSION. Influenza-attributable health care utilization is high among children with asthma and is generally higher than among healthy children.

Vaccine Effectiveness Against Laboratory-Confirmed Influenza in Children 6 to 59 Months of Age During the 2003–2004 and 2004–2005 Influenza Seasons

OBJECTIVE. The goal was to estimate the effectiveness of influenza vaccination against laboratory-confirmed influenza during the 2003–2004 and 2004–2005 influenza seasons in children 6 to 59 months of age. METHODS. We conducted a case-control study with children with medically attended, acute respiratory infections who received care in an inpatient, emergency department, or outpatient clinic setting during 2 consecutive influenza seasons. All children residing in Monroe County, New York, Davidson County, Tennessee, or Hamilton County, Ohio, were enrolled prospectively at the time of acute illness and had nasal/throat swabs tested for influenza with cultures and/or polymerase chain reaction assays. Children with laboratory-confirmed influenza were case subjects and children who tested negative for influenza were control subjects. Child vaccination records from the parent and the childs physician were used to determine and to validate influenza vaccination status. Influenza vaccine effectiveness was calculated as (1 − adjusted odds ratio) × 100. RESULTS. We enrolled 288 case subjects and 744 control subjects during the 2003–2004 season and 197 case subjects and 1305 control subjects during the 2004–2005 season. Six percent and 19% of all study children were fully vaccinated according to immunization guidelines in the respective seasons. Full vaccination was associated with significantly fewer influenza-related inpatient, emergency department, or outpatient clinic visits in 2004–2005 (vaccine effectiveness: 57%) but not in 2003–2004 (vaccine effectiveness: 44%). Partial vaccination was not effective in either season. CONCLUSIONS. Receipt of all recommended doses of influenza vaccine was associated with halving of laboratory-confirmed influenza-related medical visits among children 6 to 59 months of age in 1 of 2 study years, despite suboptimal matches between the vaccine and circulating influenza strains in both years.

Population-Based Impact of Pneumococcal Conjugate Vaccine in Young Children

Objective. To determine the population impact of pneumococcal conjugate vaccine (PCV) on pneumococcal-related diseases, including pneumonia and otitis media. Methods. Using administrative data from Tennessee Medicaid and 3 commercial insurance plans in upstate New York, we measured annual rates of medical visits for pneumococcal-related diseases (pneumococcal and nonspecific pneumonia and invasive disease; otitis media) and pneumococcal-unrelated diseases (other acute respiratory illnesses). Disease rates before (1995–2000 in Tennessee; 1998–2000 in New York) and after (2000–2002) PCV licensure were calculated for children aged <2 years (eligible for PCV) and those 3 to 5 years (not routinely given PCV). Because annual variations should affect both age groups similarly and vaccine-related outcomes should preferentially decline in younger children, ratios (<2:3–5 years) of disease rates before and after PCV licensure were compared. Expected disease rates were calculated for children aged <2 years in each postvaccine year. The difference between observed and expected disease rates was the estimated vaccine effect. Results. In 2001–2002, there were 67 380 and 9485 child-years of observation for Tennessee and New York children aged <2 years, respectively. We observed fewer visits for pneumonia and invasive disease per 1000 children than expected in both regions: 20 fewer emergency department or outpatient visits in Tennessee and 33 fewer outpatient visits in New York. Otitis media visits declined by 118 and 430 per 1000 children in Tennessee and New York, respectively. Conclusions. Adding PCV to the childhood immunization schedule was associated with a 10-fold greater reduction in pneumonia and a 100-fold greater reduction in otitis media than the previously reported reduction in culture-confirmed invasive pneumococcal diseases of 1.3 episodes per 1000 children aged <2 years. Although additional studies are needed to confirm the impact of routine immunization with PCV on pneumococcal-related disease, these results suggest that its impact is substantially greater than the effects on invasive disease alone.

The Burden of Influenza in Young Children, 2004–2009

OBJECTIVE: To characterize the health care burden of influenza from 2004 through 2009, years when influenza vaccine recommendations were expanded to all children aged ≥6 months. METHODS: Population-based surveillance for laboratory-confirmed influenza was performed among children aged <5 years presenting with fever and/or acute respiratory illness to inpatient and outpatient settings during 5 influenza seasons in 3 US counties. Enrolled children had nasal/throat swabs tested for influenza by reverse transcriptase-polymerase chain reaction and their medical records reviewed. Rates of influenza hospitalizations per 1000 population and proportions of outpatients (emergency department and clinic) with influenza were computed. RESULTS: The study population comprised 2970, 2698, and 2920 children from inpatient, emergency department, and clinic settings, respectively. The single-season influenza hospitalization rates were 0.4 to 1.0 per 1000 children aged <5 years and highest for infants <6 months. The proportion of outpatient children with influenza ranged from 10% to 25% annually. Among children hospitalized with influenza, 58% had physician-ordered influenza testing, 35% had discharge diagnoses of influenza, and 2% received antiviral medication. Among outpatients with influenza, 7% were tested for influenza, 7% were diagnosed with influenza, and <1% had antiviral treatment. Throughout the 5 study seasons, <45% of influenza-negative children ≥6 months were fully vaccinated against influenza. CONCLUSIONS: Despite expanded vaccination recommendations, many children are insufficiently vaccinated, and substantial influenza burden remains. Antiviral use was low. Future studies need to evaluate trends in use of vaccine and antiviral agents and their impact on disease burden and identify strategies to prevent influenza in young infants.

Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage

BackgroundGroup A Streptococcus (GAS) causes acute tonsillopharyngitis in children, and approximately 20% of this population are chronic carriers of GAS. Antibacterial therapy has previously been shown to be insufficient at clearing GAS carriage. Bacterial biofilms are a surface-attached bacterial community that is encased in a matrix of extracellular polymeric substances. Biofilms have been shown to provide a protective niche against the immune response and antibiotic treatments, and are often associated with recurrent or chronic bacterial infections. The objective of this study was to test the hypothesis that GAS is present within tonsil tissue at the time of tonsillectomy.MethodsBlinded immunofluorescent and histological methods were employed to evaluate palatine tonsils from children undergoing routine tonsillectomy for adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis.ResultsImmunofluorescence analysis using anti-GAS antibody was positive in 11/30 (37%) children who had tonsillectomy for adenotonsillar hypertrophy and in 10/30 (33%) children who had tonsillectomy for recurrent GAS pharyngitis. Fluorescent microscopy with anti-GAS and anti-cytokeratin 8 & 18 antibodies revealed GAS was localized to the tonsillar reticulated crypts. Scanning electron microscopy identified 3-dimensional communities of cocci similar in size and morphology to GAS. The characteristics of these communities are similar to GAS biofilms from in vivo animal models.ConclusionOur study revealed the presence of GAS within the tonsillar reticulated crypts of approximately one-third of children who underwent tonsillectomy for either adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis at the Wake Forest School of Medicine.Trial RegistrationThe tissue collected was normally discarded tissue and no patient identifiers were collected. Thus, no subjects were formally enrolled.