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Objective. Respiratory syncytial virus (RSV), influenza virus, and parainfluenza viruses (PIV) cause significant morbidity in young children. Although only influenza virus infection and illness is currently vaccine-preventable, vaccines are under development for RSV and PIV. We established a prospective, active pop-ulation- based surveillance network to provide precise estimates of hospitalization rates for viral acute respira-tory illness (ARI) in young children and to measure the potential impact of enhanced vaccine usage on these rates. Methods. Prospective, active population-based sur-veillance was conducted in young children who were hospitalized for ARI from October 1, 2000, to September 30, 2001, in Monroe County, New York (Rochester area) and Davidson County, Tennessee (Nashville area). Eligi-ble children younger than 5 years were those who re-sided in surveillance counties and were hospitalized for febrile or acute respiratory illness. Viral culture and polymerase chain reaction identified viruses from nasal and throat samples obtained from all surveillance chil-dren. We measured population-based rates of hospital-ization for RSV, influenza virus, and PIV as well as demographic, clinical, and risk factor assessment for each virus. Results. Of 812 eligible hospital admissions, 592 (73%) children were enrolled. Of the enrolled children, RSV was identified in 20%, influenza in 3%, PIV in 7%, other respiratory viruses in 36%, and no detectable virus in 39%. Population-based rates of ARI hospitalizations in children younger than 5 years were 18 per 1000. Virus-positive hospitalization rates per 1000 children were 3.5 for RSV, 1.2 for PIV, and 0.6 for influenza virus. Younger age (particularly <1 year), black and Hispanic race/eth-nicity... [ABSTRACT FROM AUTHOR]

Recent studies have associated human metapneu-movirus (HMPV) infection in children with respiratory disease of similar severity as respiratory syncytial virus (RSV) infection. We studied 668 banked swab specimens (one per admission) collected from a population-based, prospective study of acute respiratory illness among inpatient children from two U.S. cities. Specimens were tested for HMPV, RSV, influenza, and parainfluenza viruses by reverse transcription-polymerase chain reaction assays. Twenty-six (3.9%) were positive for HMPV; 125 (18.7%) for RSV; 45 (6.7%) for parainfluenza 1, 2, or 3; and 23 (3.4%) for influenza. HMPV-positive children were significantly older than RSV-positive children. HMPV-positive children required medical intensive care and received supplemental oxygen in similar frequencies to RSV-positive children. Among children hospitalized with respiratory illness, the incidence of HMPV infection was less than RSV, but clinical disease severity mirrored that of RSV infection. Further investigations to better characterize HMPV infection and its clinical effect are needed. [ABSTRACT FROM AUTHOR]

We compared the rates of detection of respiratory viruses by reverse-transcription polymerase chain reaction (RT-PCR) and by conventional viral culture in 668 combined nasal and throat samples from a prospective, multicenter, population-based study of acute respiratory tract infections among hospitalized children aged <5 years. RT-PCR increased the yield of viral identification by 2-fold, compared with that of culture alone. The increased sensitivity of viral detection by RT-PCR will yield better estimates of the population burden of viral respiratory infections. [ABSTRACT FROM AUTHOR]

Abstract. The purpose of this study was to determine (1) whether preschool-age patients who utilize the emergency department (ED) are undervaccinated compared with patients having the same primary care provider and (2) whether reducing missed vaccination opportunities in the primary care office can potentially reduce the differences in undervaccination between the groups. This retrospective cohort study involved two groups: 583 ED patients, aged 4 to 48 months, who had primary care providers; and 583 control subjects randomly selected from primary care sites and matched according to date of birth and primary care site. The major outcome variable was the point prevalence of undervaccination, defined as more than 60 days past due for a vaccine at the time of the ED visit, and for control subjects, at the time of their matched patient's ED visit. Demographic variables, vaccination history, presence of chronic illness, and office utilization history were abstracted from office charts. The mean age of all patients was 20.0 months. Emergency department patients were more likely to be boys (61% vs 50%) and had more chronic illness, but did not differ racially from those in the control group. Primary care sites included a hospital-based clinic (n = 137), neighborhood health centers (n = 172), and private practices (n = 274). The undervaccination rates by primary provider type were for (1) hospital clinic ED patients 21.1%, control subjects 19.7%; (2) neighborhood health center ED patients 29.1%, control subjects 22.7%; and (3) private practice ED patients 26.6%, control subjects 14.9%. Overall, the odds... INSET: DR. "HARDLY HUMAN" HENDREN. [ABSTRACT FROM AUTHOR]

ABSTRACT. To determine the rate of childhood undervaccination, rate and types of missed opportunities (MOs) for vaccinations, and the contribution of MOs to the undervaccination of preschool-age children, the authors conducted a retrospective medical chart review in seven primary care settings in the Rochester, NY, area: a hospital clinic, a neighborhood health center, a group-model health maintenance organization, an urban group practice, a suburban group practice, a rural health center, and a rural private practice, The random sample included 1124 children having birth dates between March 15, 1988, and September 15, 1989. The main outcome measures were cumulative undervaccination rate, defined as the proportion of patients from each practice who were ever >60 days past-due :for a vaccination by 12, 18, or 24 months of age; undervaccination time, defined as the median number of months during which children were undervaccinated; number of MOs; visit types and conditions associated with the MOs; and the duration of undervaccination time attributable to MOs. The cumulative undervaccination rate by 12 months was at least 20% in each practice except for the suburban practice, where it was 4%, The frequency of MOs varied from a high of 1.8 MO per patient per year at the rural private practice to a low of 0.3 MO per patient per year at the suburban practice. More than one quarter of MOs occurred during either health supervision or follow-up visits in all practices. In 28% of visits during which an MO occurred, patients had no fever or acute illness. The impact of MOs was twice as great for children having Medicaid or no health insurance as for children covered by private insurance, Missed opportunities contributed 13% of the total undervaccination time in the suburban practice, 27% in the clinic, and more than 40% in the other practices. It is concluded that missed opportunities for vaccination occur frequently and contribute significantly to the undervaccination of pres [ABSTRACT FROM AUTHOR]

Background: The disease burden of influenza infection among children is not well established. We conducted a population-based surveillance of medical visits associated with laboratory-confirmed influenza. Methods: Eligible children were younger than five years of age, resided in three U.S. counties, and had a medical visit for an acute respiratory tract infection or fever. Nasal and throat swabs were tested for the influenza virus by viral culture and polymerase-chain-reaction assay. Epidemiologic data were collected from parental surveys and chart reviews. Children who were hospitalized were enrolled prospectively from 2000 through 2004. Population-based rates of hospitalizations associated with influenza were calculated. Children who were seen in selected pediatric clinics and emergency departments during two influenza seasons (2002–2003 and 2003–2004) were systematically enrolled. The rates of visits to clinics and emergency departments associated with influenza were estimated. Results: The average annual rate of hospitalization associated with influenza was 0.9 per 1000 children. The estimated burden of outpatient visits associated with influenza was 50 clinic visits and 6 emergency department visits per 1000 children during the 2002–2003 season and 95 clinic visits and 27 emergency department visits per 1000 children during the 2003–2004 season. Few children who had laboratory-confirmed influenza were given a diagnosis of influenza by the treating physician in the inpatient (28 percent) or outpatient (17 percent) settings. Conclusions: Among young children, outpatient visits associated with influenza were 10 to 250 times as common as hospitalizations. Few influenza infections were recognized clinically. N Engl J Med 2006;355:31-40. [ABSTRACT FROM AUTHOR]

Background: Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. Methods: We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or a low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. Results: There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. Conclusions: Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease. (N Engl J Med 1993;329:1524-30.) [ABSTRACT FROM AUTHOR]

Since its discovery in 1955, respiratory syncytial virus (RSV) has consistently been noted to be the single most important cause of lower respiratory tract illness in infants <1 year of age. RSV also causes repeat infections and significant disease throughout life. In addition to the young child, persons with compromised immune, pulmonary or cardiac systems, and the elderly have significant risk from infection. Though RSV causes the full spectrum of acute respiratory illnesses, it is most notably associated with signs and symptoms of increased airway resistance manifested as wheezing and, in the young child, diagnosed as bronchiolitis. In temperate climates, RSV occurs as yearly outbreaks usually between late fall and early spring lasting 3-4 months in a community. The timing of outbreaks varies between years and in the same year between regions and even between nearby communities. RSV can be a serious nosocomial pathogen in high risk individuals but nosocomial transmission that can often be prevented with meticulous attention to good infection control practices. High risk groups include the premature infants and persons of any age with compromised cardiac, pulmonary, or immune systems. Risk factors for infection include increased number of children in the household and day care center attendance. There are reasonable estimates of the sizable burden of RSV disease in infants and young children and the elderly but less data on disease in older children, the role of RSV in later reactive airway disease (see chapter by M.T. Lotz et al. , this volume), and RSV-associated mortality in developing countries. The available data on burden of disease suggests there are at least four potential target populations for a vaccine, the young infant, young children >4-6 months of age, pregnant women, and the elderly. A link between infection in the young infant and later reactive airway disease and mortality in developing countries is needed. Each target population has different vaccine safety and efficacy concerns and may warrant a different type of vaccine.

Objective: To determine the vaccine effectiveness (VE) of complete and partial vaccination with the pentavalent rotavirus vaccine (RV5) in the prevention of rotavirus acute gastroenteritis (AGE) hospitalizations and emergency department visits during the first 3 rotavirus seasons after vaccine introduction., Methods: Active, prospective population-based surveillance for AGE and acute respiratory infection (ARIs) in inpatient and emergency department settings provided subjects for a case-control evaluation of VE in 3 US counties from January 2006 through June 2009. Children with laboratory-confirmed rotavirus AGE (cases) were matched according to date of birth and onset of illness to 2 sets of controls: children with rotavirus-negative AGE and children with ARI. The main outcome measure was VE with complete (3 doses) or partial (1 or 2 doses) RV5 vaccination., Results: Of age-eligible children enrolled, 18% of cases, 54% of AGE controls, and 54% of ARI controls received ≥1 dose of RV5. The VE of RV5 for 1, 2, and 3 doses against all rotavirus genotypes with the use of rotavirus-negative AGE controls was 74% (95% confidence interval [CI]: 37%-90%), 88% (95% CI: 66%-96%), and 87% (95% CI: 71%-94%), respectively, and with the use of ARI controls was 73% (95% CI: 43%-88%), 88% (95% CI: 68%-95%), and 85% (95% CI: 72%-91%), respectively. The overall VE estimates were comparable during the first and second years of life and against AGE caused by different rotavirus strains., Conclusion: RV5 was highly effective in preventing severe rotavirus disease, even after a partial series, with protection persisting throughout the second year of life.

Objectives: To determine, among a commercially-insured population of late-preterm infants, utilization of healthcare resources and costs during the 1 year following a diagnosis of respiratory syncytial virus lower respiratory infection (RSV LRI)., Methods: Administrative claims for non-capitated, commercially-insured infants <1 year old were used to identify infants diagnosed with RSV LRI and unspecified bronchiolitis/pneumonia (UBP). Infants were stratified by the setting of diagnosis. Infants without evidence of RSV LRI or UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting and logged ordinary least squares models were used to examine the relationship between RSV and costs (adjusted to 2006 USD) incurred within 1 year of RSV LRI., Results: The majority of infants were 3 months or older at the time of RSV LRI or UBP diagnosis. The rate of wheezing was significantly greater for infants in the RSV LRI and UBP cohorts relative to the comparison group (p < 0.001). Infantile asthma rates were 6-9 times higher among RSV LRI and UBP infants than the comparison group. RSV LRI and UBP infants also had significantly more emergency department visits and outpatient visits than the comparison group. The marginal healthcare costs were significantly higher for RSV LRI inpatients ($24,027) and outpatients ($2703) infants than for the comparison group (all p < 0.001)., Conclusion: Commercially insured late-preterm infants with RSV infection are at high risk for recurrent wheezing and infantile asthma during the 1-year period after the initial episode and impose a significant economic burden to the healthcare system.

Limited research exists on the economic impact of respiratory syncytial virus lower respiratory infection (RSV LRI) among vulnerable infant populations. This study evaluated healthcare costs of full-term and late-preterm Medicaid infants with RSV LRI within 1 year of infection. Medicaid administrative claims were used to conduct a retrospective study of infants born 2003-2005. Full-term and late-preterm infants <1 year old were assigned to groups based on RSV LRI and unspecified bronchiolitis/pneumonia (UBP) diagnosis codes and stratified by setting of diagnosis. Infants without evidence of RSV LRI/UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting, and logged ordinary least squares models were used to examine relationship between RSV and costs incurred within 1 year of infection. RSV LRI and UBP infants, regardless of gestational age or healthcare setting, were more likely to experience respiratory diagnoses of wheezing and infantile asthma versus comparisons. Adjusted and weighted healthcare costs were significantly higher for all groups of RSV LRI and UBP infants relative to comparison infants (P < 0.001). Among late-preterm infants with inpatient and outpatient RSV, marginal costs compared with controls were $17,465 and $2,158, respectively. Costs for RSV LRI and UBP Medicaid infants are substantial. While much of the costs result from initial RSV episodes, higher post-episode costs and rates of respiratory events, procedures, and medications in RSV and UBP infants versus comparisons indicate long-term economic impact from infection and the impact is greater among late-preterm compared to full-term infants., (Copyright 2010 Wiley-Liss, Inc.)

Objective: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab., Methods: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged

There is only limited knowledge on the burden of disease due to both new (HCoV-NL63 and HKU-1) and previously discovered coronaviruses (OC43 and 229E) in children. Respiratory specimens and clinical data were prospectively collected in an active, population-based surveillance study over a 2-year period from children aged <5 years hospitalized with acute respiratory symptoms or fever. These samples were retrospectively tested by real-time RT-PCR for HCoV-NL63, HKU1, OC43, and 229E. Human coronaviruses (HCoVs) were identified in 2.2% of study children <2 years of age. Rates of HCoV-associated hospitalization per 10,000 were 10.2 (95% CI 4.3, 17.6), 4.2 (95% CI 1.9, 6.9), and 0 (95% CI 0, 3.7) in children aged <6 months, 6-23 months, and 24-59 months, respectively. Coronaviruses were identified in a modest number of hospitalized children., (Copyright 2009 Wiley-Liss, Inc.)

Objective: To determine the population-based inpatient disease burden of parainfluenza virus in children <5 years of age., Study Design: The New Vaccine Surveillance Network (NVSN) enrolled children <5 years of age who were hospitalized with febrile or acute respiratory illnesses. Surveillance hospitals admitted >95% of all hospitalized children from each county. Combined nasal turbinate/throat swabs were tested for parainfluenza virus (PIV), respiratory syncytial virus, and influenza virus with culture and reverse-transcription-polymerase chain reaction. Both parental interviews and medical chart reviews were conducted. Age-specific population-based hospitalization rates were calculated., Results: From October 2000 through September 2004, 2798 children were enrolled. A total of 191 PIVs were identified from 189 children (6.8% of enrolled: 73 PIV type 1, 23 PIV type 2, and 95 PIV type 3), compared with 521 respiratory syncytial viruses and 159 influenza viruses. Mean PIV hospitalization rates were 3.01, 1.73, 1.53, 0.39, and 1.02 per 1000 children per year for ages 0 to 5 months, 6 to 11 months, 12 to 23 months, 24 to 59 months, and 0 to 59 months, respectively., Conclusions: PIV accounted for 6.8% of all hospitalizations for fever, acute respiratory illnesses, or both in children <5 years of age. The pediatric PIV inpatient burden is substantial and highlights the need to find an effective vaccine candidate.

Background: Late-preterm infants are known to have greater morbidity and costs compared with term infants during the neonatal period, but less is known about whether these differences continue beyond this period., Objective: The purpose of this study was to examine the most common causes and costs of rehospitalization and other health care use among late-preterm and term infants throughout the first year of life., Methods: We conducted a retrospective cohort study of late-preterm (33-36 weeks' gestation) and term infants born in 2004 with > or =1 year of enrollment in a large national US database of commercially insured members. All of the reported health care services and costs were examined from the birth hospitalization through the first year of life., Results: We evaluated 1683 late-preterm and 33 745 term infants. The average length of stay of the birth hospitalization for term infants was 2.2 days, and the average cost was $2061. Late-preterm infants had a substantially longer average stay of 8.8 days and average cost of $26 054. Total first-year costs after birth discharge were, on average, 3 times as high among late-preterm infants ($12 247) compared with term infants ($4069). Late-preterm infants were rehospitalized more often than term infants (15.2% vs 7.9%). A subset of late-preterm infants that were discharged late from their birth hospitalization had the highest rates of rehospitalization and total health care costs. Higher costs during rehospitalization of late-preterm infants, especially those with a late discharge, indicate their propensity to have more severe illness., Conclusions: Late-preterm infants have greater morbidity and total health care costs than term infants, and these differences persist throughout the first year of life. Management strategies and guidelines to reduce morbidity and costs in late-preterm infants should be investigated.

Background: Although recent studies have identified new group C human rhinoviruses (HRVCs), their spectrum of pediatric disease is unknown., Objective: We sought to determine the presentation and burden of disease caused by HRVCs among young hospitalized children., Methods: We conducted prospective population-based surveillance in 2 US counties among children less than 5 years of age hospitalized with acute respiratory illness or fever from October 2001 through September 2003. Nasal/throat swabs were obtained and tested for HRVs, as determined by means of RT-PCR and then characterized by means of partial sequencing., Results: Of 1052 children enrolled and tested during the 2-year period, 167 (16%) had HRVs detected. Of 147 samples successfully sequenced, 64 were group A HRVs, 6 were group B HRVs, and 77 were HRVCs. Children with HRVCs were significantly more likely than those with group A HRVs to have underlying high-risk conditions, such as asthma (42% vs 23%, P = .023) and to have had a discharge diagnosis of asthma (55% vs 36%, P = .022)., Conclusions: Overall, HRVCs were detected in 7% of children hospitalized for fever or respiratory conditions and constituted almost half of all rhinovirus-associated hospitalizations, suggesting that this novel group causes a substantial burden of pediatric disease.

In June 2006, the Institute of Medicine (LoM), released a comprehensive study, Preterm Birth: Causes, Consequences, and Prevention. The report was a result of the IoM's efforts, in particular the Committee on Understanding Premature Birth and Assuring Healthy Outcomes, to better understand and prevent preterm birth and improve care for babies born prematurely. After its publication, a group of health care professionals came together in a roundtable session, "Preterm Infants: A Collaborative Approach to Specialized Care," to discuss the implications of the report. The following article captures the group's April 2007 discussion about the clinical and societal problems of preterm birth. It should be of interest to hospital administrators, pediatricians, third-party payers, policy makers, public health officials, academic researchers, funding agencies, allied health professionals, and others with a vested interest in curbing healthcare costs as well as what needs to be understood and done to safeguard the short- and long-term health of a most vulnerable population.

Objectives: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab., Design: Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection., Setting: A hypothetical community or university hospital., Participants: Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation., Interventions: Palivizumab prophylaxis vs no prophylaxis., Main Outcome Measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year., Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000., Conclusions: Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection.

Objective: To determine in healthy children after primary infection the persistence of human herpesvirus 6 (HHV6) DNA, the presence and frequency of HHV6 re-activation or re-infection, and the relationship of both to illness and the presence of human herpesvirus 7 (HHV7) infection., Study Design: Children 1 to 12 years of age with previous HHV6 infection were prospectively evaluated by HHV6 and HHV7 DNA polymerase chain reaction (PCR) and reverse transcription (RT)-PCR for HHV6. HHV6 plasma antibody titers were measured. Illnesses were recorded by diary, and physician records were reviewed., Results: HHV6 DNA was detected in >or=1 peripheral blood mononuclear cell (PBMC) samples in 89% of children. HHV6 reactivation and re-infection were detected by RT-PCR in 1.1% of samples. Detection of HHV6 DNA was intermittent in 76% of children and was not associated with cumulative rates of illness. Illness at a study visit was significantly associated with the absence of HHV6 and HHV7 DNA in PBMC samples and was not associated with HHV6 antibody titer or the presence of HHV6 DNA in saliva., Conclusions: HHV6 DNA persists in most children intermittently following primary infection and is unrelated to illness. Reactivation of HHV6 occurs in healthy children without apparent illness.

Premature infants and those with chronic lung disease or congenital heart disease are at high risk of severe respiratory syncytial virus (RSV) disease. Palivizumab (Synagis), a humanized anti-RSV monoclonal antibody, has been used extensively since 1998 to prevent severe RSV disease in high-risk infants. To monitor for possible palivizumab-resistant mutants, an immunofluorescence binding assay that predicts palivizumab neutralization of RSV was developed. RSV isolates were collected at 8 US sites from 458 infants hospitalized for RSV disease (1998-2002). Palivizumab bound to all 371 RSV isolates able to be evaluated, including 25 from active-palivizumab recipients. The palivizumab epitope appears to be highly conserved, even in infants receiving prophylaxis with palivizumab.