Burden of human metapneumovirus infection in young children.

BACKGROUND: The inpatient and outpatient burden of human metapneumovirus (HMPV) infection among young children has not been well established. METHODS: We conducted prospective, population-based surveillance for acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three U.S. counties from 2003 through 2009. Clinical and demographic data were obtained from parents and medical records, HMPV was detected by means of a reverse-transcriptase polymerase-chain-reaction assay, and population-based rates of hospitalization and estimated rates of outpatient visits associated with HMPV infection were determined. RESULTS: HMPV was detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Overall annual rates of hospitalization associated with HMPV infection were 1 per 1000 children less than 5 years of age, 3 per 1000 infants less than 6 months of age, and 2 per 1000 children 6 to 11 months of age. Children hospitalized with HMPV infection, as compared with those hospitalized without HMPV infection, were older and more likely to receive a diagnosis of pneumonia or asthma, to require supplemental oxygen, and to have a longer stay in the intensive care unit. The estimated annual burden of outpatient visits associated with HMPV infection was 55 clinic visits and 13 emergency department visits per 1000 children. The majority of HMPV-positive inpatient and outpatient children had no underlying medical conditions, although premature birth and asthma were more frequent among hospitalized children with HMPV infection than among those without HMPV infection. CONCLUSIONS: HMPV infection is associated with a substantial burden of hospitalizations and outpatient visits among children throughout the first 5 years of life, especially during the first year. Most children with HMPV infection were previously healthy. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).

Norovirus and medically attended gastroenteritis in U.S. children.

BACKGROUND: Cases of rotavirus-associated acute gastroenteritis have declined since the introduction of rotavirus vaccines, but the burden of norovirus-associated acute gastroenteritis in children remains to be assessed. METHODS: We conducted active surveillance for laboratory-confirmed cases of norovirus among children younger than 5 years of age with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings. The children resided in one of three U.S. counties during the years 2009 and 2010. Fecal specimens were tested for norovirus and rotavirus. We calculated population-based rates of norovirus-associated acute gastroenteritis and reviewed billing records to determine medical costs; these data were extrapolated to the U.S. population of children younger than 5 years of age. RESULTS: Norovirus was detected in 21% of young children (278 of 1295) seeking medical attention for acute gastroenteritis in 2009 and 2010, with norovirus detected in 22% (165 of 742) in 2009 and 20% (113 of 553) in 2010 (P=0.43). The virus was also detected in 4% of healthy controls (19 of 493) in 2009. Rotavirus was identified in 12% of children with acute gastroenteritis (152 of 1295) in 2009 and 2010. The respective rates of hospitalization, emergency department visits, and outpatient visits for the norovirus were 8.6, 146.7, and 367.7 per 10,000 children younger than 5 years of age in 2009 and 5.8, 134.3, and 260.1 per 10,000 in 2010, with an estimated cost per episode of $3,918, $435, and $151, respectively, in 2009. Nationally, we estimate that the average numbers of annual hospitalizations, emergency department visits, and outpatient visits due to norovirus infection in 2009 and 2010 among U.S. children in this age group exceeded 14,000, 281,000, and 627,000, respectively, with more than $273 million in treatment costs each year. CONCLUSIONS: Since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute gastroenteritis in U.S. children and is associated with nearly 1 million health care visits annually. (Funded by the Centers for Disease Control and Prevention.).

Clinical and epidemiologic features of respiratory syncytial virus.

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.

Comparison of 2 assays for diagnosing rotavirus and evaluating vaccine effectiveness in children with gastroenteritis.

We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%-91%]) in EIA-positive children but offered no significant protection (14% [95% CI -105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients.

Disparities between black and white children in hospitalizations associated with acute respiratory illness and laboratory-confirmed influenza and respiratory syncytial virus in 3 US counties--2002-2009.

Few US studies have assessed racial disparities in viral respiratory hospitalizations among children. This study enrolled black and white children under 5 years of age who were hospitalized for acute respiratory illness (ARI) in 3 US counties during October-May 2002-2009. Population-based rates of hospitalization were calculated by race for ARI and laboratory-confirmed influenza and respiratory syncytial virus (RSV), using US Census denominators. Relative rates of hospitalization between racial groups were estimated. Of 1,415 hospitalized black children and 1,824 hospitalized white children with ARI enrolled in the study, 108 (8%) black children and 111 (6%) white children had influenza and 230 (19%) black children and 441 (29%) white children had RSV. Hospitalization rates were higher among black children than among white children for ARI (relative rate (RR) = 1.7, 95% confidence interval (CI): 1.6, 1.8) and influenza (RR = 2.1, 95% CI: 1.6, 2.9). For RSV, rates were similar among black and white children under age 12 months but higher for black children aged 12 months or more (for ages 12-23 months, RR = 1.7, 95% CI: 1.1, 2.5; for ages 24-59 months, RR = 2.2, 95% CI: 1.3, 3.6). Black children versus white children were significantly more likely to have public insurance or no insurance (85% vs. 43%) and a history of asthma/wheezing (28% vs. 18%) but not more severe illness. The observed racial disparities require further study.

Chromosomally integrated human herpesvirus 6: questions and answers.

Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease.

Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children.

BACKGROUND: The contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear. OBJECTIVE: To assess the association between HRV species detection and ARI hospitalizations. METHODS: Children <5 years old hospitalized for ARI were prospectively enrolled between December 2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled between December 2003 and March 2004 and between October 2004 and April 2005 in clinics. Nasal and throat swab samples were tested for HRV and other viruses (ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, and influenza virus) by reverse-transcription-polymerase chain reaction, and genetic sequencing identified HRV species and types. HRV species detection was compared between controls and patients hospitalized during months in which controls were enrolled. RESULTS: A total of 1867 children with 1947 ARI hospitalizations and 784 controls with 790 clinic visits were enrolled and tested for HRV. The HRV-A detection rate among participants ≥24 months old was 8.1% in the hospitalized group and 2.2% in the control group (P = .009), and the HRV-C detection rates among those ≥6 months old were 8.2% and 3.9%, respectively (P = .002); among younger children, the detection rates for both species were similar between groups. The HRV-B detection rate was ≤1%. A broad diversity of HRV types was observed in both groups. Clinical presentations were similar among HRV species. Compared with children infected with other viruses, children with HRV detected were similar for severe hospital outcomes and more commonly had histories or diagnoses of asthma or wheezing. CONCLUSIONS: HRV-A and HRV-C were associated with ARI hospitalization and serious illness outcomes.

Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US Counties, 2006-2009.

BACKGROUND: Routine rotavirus vaccination of US infants began in 2006. We conducted active, population-based surveillance for rotavirus gastroenteritis hospitalizations in 3 US counties to assess vaccine impact. METHODS: Children <36 months old hospitalized with diarrhea and/or vomiting were enrolled from January through June each year during the period 2006-2009 and tested for rotavirus. Age-stratified rates of hospitalization for rotavirus infection were compared with corresponding vaccination coverage among a control group of children with acute respiratory illness. To assess direct and indirect benefits, vaccination coverage rates in the control group were multiplied by vaccine effectiveness estimates to calculate expected reductions in the rate of hospitalization for rotavirus infection. Rotavirus serotypes were compared across years. RESULTS: Compared with 2006, a significant reduction in rates of hospitalization for rotavirus infection (P < .001) was observed in 2008 among all age groups. There was an 87% reduction in the 6-11-month-old age group (coverage, 77%), a 96% reduction in the 12-23-months-old age group (coverage, 46%), and a 92% reduction in the 24-35-month-old age group (coverage, 1%), which exceeded reductions expected on the basis of coverage and vaccine effectiveness estimates. Age-specific rate reductions were nearly equivalent to those expected on the basis of age-specific vaccine coverage in 2009. Predominant strains varied annually: G1P[8] (91%) in 2006; G1P[8] (45%) and G12P[8] (36%) in 2007; G1P[8] (89%) in 2008; and G3P[8] (43%), G2P[4] (34%), and G9P[8] (27%) in 2009. CONCLUSIONS: Rotavirus vaccination has dramatically decreased rates of hospitalization for rotavirus infection among children in these US counties. In 2008, reductions were prominent among both vaccine-eligible age groups and older, largely unvaccinated children; the latter likely resulted from indirect protection. Although rates among age groups eligible for vaccination remained low in 2009, indirect benefits disappeared.

Population-based incidence of human metapneumovirus infection among hospitalized children.

BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established. METHODS: We conducted population-based prospective surveillance for 2 years in 2 US counties of HMPV infection among children <5 years old who were hospitalized with ARI or fever. Nasal and throat specimens obtained with swabs were tested for HMPV by real-time reverse-transcription polymerase chain reaction and genotyped. RESULTS: Forty-two (3.8%) of 1104 children tested positive for HMPV. The overall annual rate of HMPV-associated hospitalizations per 1000 children <5 years old was 1.2 (95% confidence interval [CI], 0.9-1.6). This rate was highest among infants 0-5 months old (4.9 per 1000 [95% CI, 2.9-7.2]), followed by children 6-11 months old (2.9 per 1000 [95% CI, 1.4-4.7]). The annual rate of hospitalization for HMPV infection was less than that for respiratory syncytial virus infection but similar to that for influenza and parainfluenza virus 3 infection in all age groups. The mean age of children hospitalized with HMPV infection was 6 months. Bronchiolitis, pneumonia, and asthma were the most common diagnoses among children with HMPV infection. All 4 HMPV subgroups were detected during both years at both sites. HPMV infection was most prominent from March through May. CONCLUSION: HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza virus and parainfluenza virus 3.

A novel group of rhinoviruses is associated with asthma hospitalizations.

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.

Underestimates of intussusception rates among US infants based on inpatient discharge data: implications for monitoring the safety of rotavirus vaccines.

BACKGROUND: Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short-stay or emergency department care. METHODS: Intussusception cases occurring in infants were identified retrospectively at 3 children's hospitals from January 2001 through March 2006, a period without rotavirus vaccine use, by a search of discharge, billing, and radiology databases for International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0 (intussusception) and procedure codes and by review of medical records. RESULTS: Of 156 infants with intussusception fulfilling Brighton level 1 criteria, 81 (52%) were billed as inpatients, 68 (44%) as short-stay patients, and 7 (4%) as emergency department patients only. The use of only inpatients assigned code 560.0 underestimated the total number of level 1 cases at the hospitals by 44%. The mean annual intussusception rate for the hospitals' catchment counties was 49.3 cases per 100,000 live births (inpatient cases: 27.1 cases per 100,000 live births; short-stay or emergency department cases: 22.3 cases per 100,000 live births). CONCLUSIONS: Intussusception rates based solely on inpatient discharge databases could underestimate the true incidence of level 1 intussusception by >40%. Background rates used for assessment of risk after vaccination should account for cases managed only with short-stay or emergency department care.

The underrecognized burden of influenza in young children.

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.

Parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization.

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.

Coronavirus infection and hospitalizations for acute respiratory illness in young children.

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.

Real-time reverse transcription-PCR assay for comprehensive detection of human rhinoviruses.

Human rhinoviruses (HRVs) are important contributors to respiratory disease, but their healthcare burden remains unclear, primarily because of the lack of sensitive, accurate, and convenient means of determining their causal role. To address this, we developed and clinically validated the sensitivity and specificity of a real-time reverse transcription-PCR (RT-PCR) assay targeting the viral 5' noncoding region defined by sequences obtained from all 100 currently recognized HRV prototype strains and 85 recently circulating field isolates. The assay successfully amplified all HRVs tested and could reproducibly detect 50 HRV RNA transcript copies, with a dynamic range of over 7 logs. In contrast, a quantified RNA transcript of human enterovirus 68 (HEV68) that showed the greatest sequence homology to the HRV primers and probe set was not detected below a concentration of 5 x 10(5) copies per reaction. Nucleic acid extracts of 111 coded respiratory specimens that were culture positive for HRV or HEV were tested with the HRV real-time RT-PCR assay and by two independent laboratories that used different in-house HRV/HEV RT-PCR assays. Eighty-seven HRV-culture-positive specimens were correctly identified by the real-time RT-PCR assay, and 4 of the 24 HEV-positive samples were positive for HRV. HRV-specific sequences subsequently were identified in these four specimens, suggesting HRV/HEV coinfection in these patients. The assay was successfully applied in an investigation of a coincidental outbreak of HRV respiratory illness among laboratory staff.

Preemie abandonment? Multidisciplinary experts consider how to best meet preemies needs at "preterm infants: a collaborative approach to specialized care" roundtable.

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.

Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease.

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.

Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤ 24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.

Transmission of influenza: implications for control in health care settings.

Annual influenza epidemics in the United States result in an average of >36,000 deaths and 114,000 hospitalizations. Influenza can spread rapidly to patients and health care personnel in health care settings after influenza is introduced by visitors, staff, or patients. Influenza outbreaks in health care facilities can have potentially devastating consequences, particularly for immunocompromised persons. Although vaccination of health care personnel and patients is the primary means to prevent and control outbreaks of influenza in health care settings, antiviral influenza medications and isolation precautions are important adjuncts. Although droplet transmission is thought to be the primary mode of influenza transmission, limited evidence is available to support the relative clinical importance of contact, droplet, and droplet nuclei (airborne) transmission of influenza. In this article, the results of studies on the modes of influenza transmission and their relevant isolation precautions are reviewed.

Guidelines for palivizumab prophylaxis: are they based on infant's risk of hospitalization for respiratory syncytial viral disease?

BACKGROUND: The American Academy of Pediatrics (AAP) guidelines for respiratory syncytial virus (RSV) prophylaxis aim to prioritize palivizumab administration to infants at highest risk for RSV disease. Multiple studies have been published that assess the risk of hospitalization for RSV disease by gestational age (GA) at birth and severity of lung disease. OBJECTIVE: To evaluate whether the AAP guidelines for RSV prophylaxis correlate with the available data in the literature on the degree of risk of hospitalization for RSV disease by GA at birth and severity of lung disease. METHODS: We considered a hypothetical population of infants with and without chronic lung disease. This population was then divided into hypothetical cohorts depending on GA at birth and month of neonatal intensive care unit discharge. We assumed that infants are discharged from neonatal intensive care unit at 36 to 37 weeks postconceptional age. By applying the AAP policy for RSV prophylaxis, the numbers of palivizumab injections were determined for the different cohorts. RESULTS: In some instances infants who are currently known to be at higher risk of hospitalization for RSV disease receive fewer palivizumab injections than infants known to be at lower risk. CONCLUSION: Some discrepancies exist between the RSV prophylaxis guidelines and the published data on the level of risk of hospitalization for RSV disease by GA and lung disease. AAP policy for RSV prophylaxis must be amended to better correlate the amount of palivizumab prophylaxis with the level of risk of hospitalization for RSV disease as determined by the above factors.