[show abstract][hide abstract] ABSTRACT: It is unclear whether the infectious etiology of severe bronchiolitis affects short-term outcomes, such as post-hospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse.
We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007 to 2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent bronchiolitis visit or scheduled visit at which additions to the bronchiolitis medications were made) during the 2 weeks after hospital discharge.
Among 1836 enrolled children with 2-week follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV co-infection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (OR, 0.99; 95%CI, 0.52-1.90; P=0.98), whereas those with RSV/RV co-infection were more likely to have relapse (OR, 1.54; 95%CI, 1.03-2.30; P=0.03).
In this prospective, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that RSV/RV co-infection was independently associated with a higher likelihood of bronchiolitis relapse. Present data support the concept that the infectious etiology of severe bronchiolitis affects short-term outcomes.
The Pediatric Infectious Disease Journal 02/2014; · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Among 20 children admitted with laboratory-confirmed influenza, viral RNA was detected in respiratory secretion, stool and blood in 19, 5 and 1 children, respectively. Gastrointestinal symptoms were common but were not associated with viral RNA in stool. nH1N1 viremia was detected, for the first time, in an immunocompetent child.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE:To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis.METHODS:We enrolled 2207 children, aged <2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth <37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea.RESULTS:Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%-6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age ≥6 months; birth weight <2.3 kg (5 pounds; OR 2.15), compared with ≥3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation <90% (OR 1.60). Apnea risk was similar across the major viral pathogens.CONCLUSIONS:In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus.Findings and conclusions: Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request.
[show abstract][hide abstract] ABSTRACT: BACKGROUND:: Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department (ED) utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to better understand the systemic host response to acute RSV bronchiolitis in infants and young children. METHODS:: Patients (age ≤ 24 months) who were clinically diagnosed with acute bronchiolitis and who had a positive rapid test for RSV assay were recruited from the Texas Children's Hospital ED. Global gene expression of peripheral whole blood cells were analyzed in 21 cases and 37 age-matched healthy controls. Transcripts exhibiting significant upregulation and downregulation as a result of RSV infection were identified and confirmed in a subset of samples using RNAseq. The potential pathways affected were analyzed. RESULTS:: Blood was obtained from patients with acute RSV bronchiolitis (mean age 6 months). Of these, 43% were admitted to the hospital, 52% were given intravenous fluids and 24% received oxygen. Highly significant expression differences were detected in a discovery cohort of White infants (N=33) and validated in an independent group of African American infants (N=19). Individuals with mild disease (N=15) could not be distinguished from subjects with clinically moderate disease (N=5). Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network. There was a significant downregulation of transcripts corresponding to antigen presentation.
The Pediatric Infectious Disease Journal 11/2012; · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine. METHODS: Six formulations with (5, 15, 30 and 60μg) and without (30 and 60μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. RESULTS: The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. CONCLUSIONS: The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419.
[show abstract][hide abstract] ABSTRACT: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis.
We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens.
There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1-1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95% CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80.
In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began.
[show abstract][hide abstract] ABSTRACT: We reexamined the finding of an inverse relationship between values of nasopharyngeal lactate dehydrogenase, a marker of the innate immune response, and bronchiolitis severity. In a prospective, multicenter study of 258 children, we found in a multivariable model that higher nasopharyngeal lactate dehydrogenase values in young children with bronchiolitis were independently associated with a decreased risk of hospitalization.
[show abstract][hide abstract] ABSTRACT: To determine whether hospital length of stay(LOS) for acute bronchiolitis is influenced by the infecting pathogen.
A prospective observational cohort study was performed during 3 consecutive years.
Sixteen US hospitals participated in the study.
Children younger than 2 years hospitalized with bronchiolitis were included.
The results of nasopharyngeal aspirate polymerase chain reaction pathogen testing served as the main exposure.
Hospital LOS was determined.
Of 2207 participants, 72.0% had respiratory syncytial virus (RSV) and 25.6% had human rhinovirus(HRV); the incidence of each of the other viruses and bacteria was 7.8% or less. Multiple pathogen infections were present in 29.8% of the children. There were 1866 children(84.5%) with RSV and/or HRV. Among these 1866 children, the median age was 4 months and 59.5% were male. The median LOS was 2 days (interquartile range,1-4 days). Compared with children who had only RSV,an LOS of 3 or more days was less likely among children with HRV alone (adjusted odds ratio [AOR], 0.36; 95%CI, 0.20-0.63; P.001) and those with HRV plus non-RSV pathogens (AOR, 0.39; 95% CI, 0.23-0.66; P.001)but more likely among children with RSV plus HRV(AOR,1.33; 95% CI, 1.02-1.73; P=.04), controlling for 15 demographic and clinical factors.
In this multicenter study of children hospitalized with bronchiolitis, RSV was the most common virus detected, but HRV was detected in one-quarter of the children. Since 1 in 3 children had multiple virus infections and HRV was associated with LOS, these data challenge the effectiveness of current RSV-based cohorting practices, the sporadic testing for HRV in bronchiolitis research, and current thinking that the infectious etiology of severe bronchiolitis does not affect short-term outcomes.
Archives of pediatrics & adolescent medicine 04/2012; 166(8):700-6. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic.
Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR.
Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002).
Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner.
The Open Respiratory Medicine Journal 01/2012; 6:127-34.
[show abstract][hide abstract] ABSTRACT: We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of 364 persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific reverse transcription-PCR (RT-PCR) assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years of age and 25 to 37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza viruses.
Journal of clinical microbiology 11/2011; 50(2):506-8. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Influenza is an uncontrolled epidemic disease that is vaccine preventable. New recommendations for universal immunization present a challenge to the implementation of vaccine delivery. This field trial examines the effectiveness of school-based clinics for vaccine delivery before an epidemic caused by 3 new influenza virus variants not contained in the vaccine.
Live attenuated influenza vaccine (LAIV) was offered to eligible children in elementary schools of eastern Bell County, Texas. Age-specific rates of medically attended acute respiratory illness for health plan members at the intervention site were compared with those for members at comparison sites during the epidemic, defined by viral surveillance at all sites.
Almost 48% of children in elementary schools were vaccinated. Significant herd protection attributed to LAIV was detected for all age groups except 12-17-year-old students, who were not offered free vaccine. Approximately 2500 medical encounters were prevented at the intervention site. Inactivated vaccine provided marginal protection against the epidemic viruses.
LAIV delivered to elementary-school children before an epidemic caused by 3 new variant influenza viruses generated significant cross-protection for the recipients and indirect (herd) protection for the community.
The Journal of Infectious Diseases 10/2010; 202(11):1626-33. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: To identify the frequency of outpatient, non-hospitalized visits for respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) among children and high-risk infants.
Published studies that reported population-based rates of outpatient RSV illness were reviewed. In addition, we conducted a retrospective cohort study from a national claims database including preterm and full term infants born between April 2004 and April 2006 <6 months of age and continuously enrolled through their first RSV season.
In the selected published studies, rates of outpatient RSV LRI were highest among infants and young children (ranging from 6.9 to 11 per 1,000 children age 1-4 years to 157.5 to 252.0 per 1,000 children age <1 year). In the cohort study, rates of outpatient RSV LRI among preterm infants <or=32 wGA or with chronic lung disease (CLD) ranged from 158.7 to 272.6 visits per 1,000 children. Rates for late preterm (33-36 wGA) infants ranged from 183.3 to 245.7 per 1,000, which was higher than full term infants (128.8 to 171.3 per 1,000).
Approximately 1 in every 5 of high-risk infants will be affected during their first RSV season, which indicates a fairly high and unrecognized reservoir of disease. Outpatient RSV LRI visits increase with younger age and prematurity.
[show abstract][hide abstract] ABSTRACT: Because the decision to hospitalize an infant with bronchiolitis is often supported by subjective criteria and objective indicators of bronchiolitis severity are lacking, we tested the hypothesis that lactate dehydrogenase (LDH), which is released from injured cells, is a useful biochemical indicator of bronchiolitis severity.
We retrospectively analyzed a study of children <24 months old presenting to the emergency department with bronchiolitis. Demographic, clinical information, nasal wash (NW), and serum specimens were obtained. NW samples were analyzed for respiratory viruses, caspase 3/7 activity, and a panel of cytokines and chemokines. Total LDH activity was tested in NW samples and sera.
Of 101 enrolled children (median age: 5.6 months), 98 had NW specimens available. A viral etiology was found for 82 patients (83.6%), with respiratory syncytial virus (RSV) (66%) and rhinovirus (19%) being the most common viruses detected. Concentrations of LDH in NW specimens were independent from those in sera and were higher in children with RSV infection or with dual infection. Significant correlations were found between NW LDH and NW cytokines/chemokines. Similarly, NW LDH correlated with NW-caspase 3/7 activity (r = 0.75; P < .001). In a multivariate analysis, NW LDH concentration in the upper quartile was significantly associated with a reduced risk of hospitalization (odds ratio: 0.19 [95% confidence interval: 0.05-0.68]; P = .011).
NW LDH levels in young children with bronchiolitis varied according to viral etiology and disease severity. Values in the upper quartile were associated with approximately 80% risk reduction in hospitalization, likely reflecting a robust antiviral response. NW LDH may be a useful biomarker to assist the clinician in the decision to hospitalize a child with bronchiolitis.
[show abstract][hide abstract] ABSTRACT: This study investigated the influence of oseltamivir on influenza-related complications and hospitalizations for children and adolescents, 1 to 17 years of age, with chronic medical conditions or neurologic or neuromuscular disease.
In a retrospective study, outcomes for patients who were given oseltamivir within 1 day after influenza diagnosis were compared with those for patients who received no antiviral therapy. Anonymous data from MarketScan databases (Thomson Reuters, Cambridge, MA) were used to identify patients from 6 influenza seasons between 2000 and 2006. The study outcomes were frequencies of pneumonia, respiratory illnesses other than pneumonia, otitis media, and hospitalization.
Oseltamivir was prescribed for 1634 patients according to the study criteria, and 3721 patients received no antiviral therapy for their influenza. After adjustment for demographic and medical history variables, oseltamivir was associated with significant reductions in the risks of respiratory illnesses other than pneumonia, otitis media and its complications, and all-cause hospitalization in the 14 days after influenza diagnosis. Analyses for 30 days after influenza diagnosis also showed significant risk reductions for respiratory illnesses other than pneumonia, otitis media and its complications, and all-cause hospitalization with oseltamivir.
When it was prescribed at influenza diagnosis, oseltamivir was associated with reduced risks of influenza-related complications and hospitalizations for children and adolescents at high risk of influenza complications.
[show abstract][hide abstract] ABSTRACT: High rates of vaccination coverage for preschool and school-aged children can reduce morbidity and mortality related to influenza outbreak. More focused and effective influenza prevention strategies are necessary to improve quality of life and to limit the burden of flu complications.
Managed care (Langhorne, Pa.) 11/2008; 17(10 Suppl 10):8-14.
[show abstract][hide abstract] ABSTRACT: Human metapneumovirus (hMPV), a member of the family Paramyxoviridae, is a leading cause of lower respiratory tract infections in children, the elderly, and immunocompromised patients. Virus- and host-specific mechanisms of pathogenesis and immune protection are not fully understood. By an intranasal inoculation model, we show that hMPV-infected BALB/c mice developed clinical disease, including airway obstruction and hyperresponsiveness (AHR), along with histopathologic evidence of lung inflammation and viral replication. hMPV infection protected mice against subsequent viral challenge, as demonstrated by undetectable viral titers, lack of body weight loss, and a significant reduction in the level of lung inflammation. No cross-protection with other paramyxoviruses, such as respiratory syncytial virus, was observed. T-lymphocyte depletion studies showed that CD4(+) and CD8(+) T cells cooperate synergistically in hMPV eradication during primary infection, but CD4(+) more than CD8(+) T cells also enhanced clinical disease and lung pathology. Concurrent depletion of CD4(+) and CD8(+) T cells completely blocked airway obstruction as well as AHR. Despite impaired generation of neutralizing anti-hMPV antibodies in the absence of CD4(+) T cells, mice had undetectable viral replication after hMPV challenge and were protected from clinical disease, suggesting that protection can be provided by an intact CD8(+) T-cell compartment. Whether these findings have implications for naturally acquired human infections remains to be determined.
Journal of Virology 07/2008; 82(17):8560-9. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adenovirus (Ad)14 has recently emerged in the United States causing outbreaks of severe respiratory disease. To determine if Ad14 circulated in Houston, Texas, during the same time as an outbreak in military recruits in nearby San Antonio, 215 pediatric adenovirus isolates were serotyped using microneutralization. None were Ad14; Ad1, Ad2, and Ad3 were the most common identified serotypes.