Winter air pollution and infant bronchiolitis in Paris.

PubMed

Ségala, Claire; Poizeau, David; Mesbah, Mounir; Willems, Sylvie; Maidenberg, Manuel

2008-01-01

Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens in infants and young children. It is not known why some previously healthy infants, when in contact with RSV, develop bronchiolitis whereas others have only mild symptoms. Our study aimed to evaluate the possible association between emergency hospital visits for bronchiolitis and air pollution in the Paris region during four winter seasons. We included children under the age of 3 years who attended emergency room services for bronchiolitis (following standardized definition) during the period 1997-2001. Two series of data from 34 hospitals, the daily number of emergency hospital consultations (n=50857) and the daily number of hospitalizations (n=16588) for bronchiolitis, were analyzed using alternative statistical methods; these were the generalized additive model (GAM) and case-crossover models. After adjustments for public holidays, holidays and meteorological variables the case-crossover model showed that PM10, BS, SO2 and NO2 were positively associated with both consultations and hospitalizations. GAM models, adjusting for long-term trend, seasonality, holiday, public holiday, weekday and meteorological variables, gave similar results for SO2 and PM10. This study shows that air pollution may act as a trigger for the occurrence of acute severe bronchiolitis cases.

Respiratory Syncytial Virus Infections

MedlinePlus

Respiratory syncytial virus (RSV) causes mild, cold-like symptoms in adults and older healthy children. It can cause serious problems in ... tests can tell if your child has the virus. There is no specific treatment. You should give ...

Respiratory Syncytial Virus (RSV)

MedlinePlus

... It's been added to your dashboard . Respiratory syncytial virus (RSV) is a common virus that infects the lungs and breathing passages. Almost ... antiviral is medicine that kills infections caused by viruses. How can you help protect your baby from ...

Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

PubMed

Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

2018-01-01

Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

PubMed Central

Mei, Minghua; Mehta, Reena

2017-01-01

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness. PMID:28267794

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

PubMed

Piedra, Felipe-Andrés; Mei, Minghua; Avadhanula, Vasanthi; Mehta, Reena; Aideyan, Letisha; Garofalo, Roberto P; Piedra, Pedro A

2017-01-01

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.

Diagnosis and management of bronchiolitis.

PubMed

2006-10-01

Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection. It is the most common lower respiratory infection in this age group. It is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, increased mucus production, and bronchospasm. The American Academy of Pediatrics convened a committee composed of primary care physicians and specialists in the fields of pulmonology, infectious disease, emergency medicine, epidemiology, and medical informatics. The committee partnered with the Agency for Healthcare Research and Quality and the RTI International-University of North Carolina Evidence-Based Practice Center to develop a comprehensive review of the evidence-based literature related to the diagnosis, management, and prevention of bronchiolitis. The resulting evidence report and other sources of data were used to formulate clinical practice guideline recommendations. This guideline addresses the diagnosis of bronchiolitis as well as various therapeutic interventions including bronchodilators, corticosteroids, antiviral and antibacterial agents, hydration, chest physiotherapy, and oxygen. Recommendations are made for prevention of respiratory syncytial virus infection with palivizumab and the control of nosocomial spread of infection. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent comprehensive peer review before it was approved by the American Academy of Pediatrics. This clinical practice guideline is not intended as a sole source of guidance in the management of children with bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It is not intended to replace clinical judgment or establish a protocol for the care of all children with this condition. These recommendations may not provide the only appropriate approach to the management of children

Respiratory Syncytial Virus (RSV) Test: MedlinePlus Lab Test Information

MedlinePlus

... this page: https://medlineplus.gov/labtests/respiratorysyncytialvirusrsvtest.html Respiratory Syncytial Virus (RSV) Test To use the sharing ... is an RSV test? RSV , which stands for respiratory syncytial virus, is an infection that affects the ...

Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

PubMed

Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun

2017-04-01

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged <1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness <14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Influenza and respiratory syncytial virus are the major respiratory viruses detected from prospective testing of pediatric and adult coronial autopsies.

PubMed

Speers, David J; Moss, Daniel M; Minney-Smith, Cara; Levy, Avram; Smith, David W

2013-11-01

To ascertain the full mortality of influenza and other respiratory viruses, the testing of community autopsy specimens is essential. Respiratory virus PCR and culture were performed on 2418 fresh unfrozen respiratory samples collected from 1611 coronial cases where the death was either unknown or infection was suspected, from July 2007 to June 2011, to detect the common respiratory viruses in children and adults, using standardized microbiological testing. The respiratory virus positive rate was 8·3% (134 cases) with a peak of 28% (42 of 151 cases) in children under 10 years of age. Influenza virus was the commonest respiratory virus (50 cases, 3%), followed by respiratory syncytial virus (RSV) (30 cases, 2%). All tested respiratory viruses were found in children, most commonly adenovirus, enterovirus and RSV, and influenza A and RSV predominated in those over 60 years, but coinfection was uncommon. Almost all influenza cases occurred when influenza was widely circulating in the community but few were diagnosed pre-mortem. Influenza and RSV detection was associated with bronchitis or bronchiolitis in 7 (9%) of the 80 cases and caused pneumonia in 14 (0·8%) deaths overall. Our prospective review of respiratory viruses using standardized testing found a single lower respiratory tract autopsy specimen for respiratory virus PCR would detect most community infections at the time of death. © 2013 John Wiley & Sons Ltd.

Severity of viral coinfection in hospitalized infants with respiratory syncytial virus infection.

PubMed

De Paulis, Milena; Gilio, Alfredo Elias; Ferraro, Alexandre Archanjo; Ferronato, Angela Esposito; do Sacramento, Patrícia Rossi; Botosso, Viviane Fongaro; Oliveira, Danielle Bruna Leal de; Marinheiro, Juliana Cristina; Hársi, Charlotte Marianna; Durigon, Edison Luiz; Vieira, Sandra Elisabete

2011-01-01

To compare the severity of single respiratory syncytial virus (RSV) infections with that of coinfections. A historical cohort was studied, including hospitalized infants with acute RSV infection. Nasopharyngeal aspirate samples were collected from all patients to detect eight respiratory viruses using molecular biology techniques. The following outcomes were analyzed: duration of hospitalization and of oxygen therapy, intensive care unit admission and need of mechanical ventilation. Results were adjusted for confounding factors (prematurity, age and breastfeeding). A hundred and seventy six infants with bronchiolitis and/or pneumonia were included in the study. Their median age was 4.5 months. A hundred and twenty one had single RSV infection and 55 had coinfections (24 RSV + adenovirus, 16 RSV + human metapneumovirus and 15 other less frequent viral associations). The four severity outcomes under study were similar in the group with single RSV infection and in the coinfection groups, independently of what virus was associated with RSV. Virus coinfections do not seem to affect the prognosis of hospitalized infants with acute RSV infection.

Bronchiolitis: the new American Academy of Pediatrics guidelines.

PubMed

Corsello, G

2007-10-01

Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTI) in young children worldwide. RSV is an important cause of LRTI in infants and a variety of factors, such as gender, age at admission, gestational age, birth weight, and exposure to tobacco smoke and breast feeding may affect the prevalence of RSV-related disease and, possibly, the risk of developing asthma-like symptoms during the school years. AAP in 2006 formulated the new guidelines on diagnosis and management of bronchiolitis, giving recommendations on different conditions requesting clinical decisions also in terms of prevention.

Respiratory syncytial virus infection in cattle

USDA-ARS?s Scientific Manuscript database

Bovine respiratory syncytial virus (bRSV) is a cause of respiratory disease in cattle world-wide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bRSV infection can predispose calves to secondary bacterial infection by org...

Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia.

PubMed

Hogan, Alexandra B; Anderssen, Robert S; Davis, Stephanie; Moore, Hannah C; Lim, Faye J; Fathima, Parveen; Glass, Kathryn

2016-09-01

Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

Immunomodulatory constituents of human milk change in response to infant bronchiolitis.

PubMed

Bryan, Dani-Louise; Hart, Prue H; Forsyth, Kevin D; Gibson, Robert A

2007-09-01

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p < or = 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non-specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast-fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

MedlinePlus

... of Search Controls Search Form Controls Cancel Submit Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled ... 2018 Content source: National Center for Immunization and Respiratory Diseases (NCIRD) , Division of Viral Diseases Email Recommend ...

Office-based treatment and outcomes for febrile infants with clinically diagnosed bronchiolitis.

PubMed

Luginbuhl, Lynn M; Newman, Thomas B; Pantell, Robert H; Finch, Stacia A; Wasserman, Richard C

2008-11-01

The goals were to describe the (1) frequency of sepsis evaluation and empiric antibiotic treatment, (2) clinical predictors of management, and (3) serious bacterial illness frequency for febrile infants with clinically diagnosed bronchiolitis seen in office settings. The Pediatric Research in Office Settings network conducted a prospective cohort study of 3066 febrile infants (<3 months of age with temperatures >or=38 degrees C) in 219 practices in 44 states. We compared the frequency of sepsis evaluation, parenteral antibiotic treatment, and serious bacterial illness in infants with and without clinically diagnosed bronchiolitis. We identified predictors of sepsis evaluation and parenteral antibiotic treatment in infants with bronchiolitis by using logistic regression models. Practitioners were less likely to perform a complete sepsis evaluation, urine testing, and cerebrospinal fluid culture and to administer parenteral antibiotic treatment for infants with bronchiolitis, compared with those without bronchiolitis. Significant predictors of sepsis evaluation in infants with bronchiolitis included younger age, higher maximal temperature, and respiratory syncytial virus testing. Predictors of parenteral antibiotic use included initial ill appearance, age of <30 days, higher maximal temperature, and general signs of infant distress. Among infants with bronchiolitis (N = 218), none had serious bacterial illness and those with respiratory distress signs were less likely to receive parenteral antibiotic treatment. Diagnoses among 2848 febrile infants without bronchiolitis included bacterial meningitis (n = 14), bacteremia (n = 49), and urinary tract infection (n = 167). In office settings, serious bacterial illness in young febrile infants with clinically diagnosed bronchiolitis is uncommon. Limited testing for bacterial infections seems to be an appropriate management strategy.

Respiratory Support in Bronchiolitis: Trial Evidence.

PubMed

Cunningham, Steve

2018-05-01

Acute viral lower respiratory tract infection is frequently associated with hypoxemia and respiratory distress, sometimes progressing to hypercarbia and respiratory failure. In recent years, trials have assessed the effects of oxygen supplementation and respiratory support with high-flow oxygen therapy. An oxygen saturation target of 90% is as safe and clinically effective as 94% in infants with bronchiolitis. Trials of high-flow humidified oxygen have demonstrated safety, but as yet poorly demarcated an appropriate place for use within the clinical course of the disease. Effective trials of continuous positive airway pressure are lacking and urgently required. The trials reported to date have highlighted the need for common outcomes in relation to treatment failure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Virus Type and Genomic Load in Acute Bronchiolitis: Severity and Treatment Response With Inhaled Adrenaline.

PubMed

Skjerven, Håvard O; Megremis, Spyridon; Papadopoulos, Nikolaos G; Mowinckel, Petter; Carlsen, Kai-Håkon; Lødrup Carlsen, Karin C

2016-03-15

Acute bronchiolitis frequently causes infant hospitalization. Studies on different viruses or viral genomic load and disease severity or treatment effect have had conflicting results. We aimed to investigate whether the presence or concentration of individual or multiple viruses were associated with disease severity in acute bronchiolitis and to evaluate whether detected viruses modified the response to inhaled racemic adrenaline. Nasopharyngeal aspirates were collected from 363 infants with acute bronchiolitis in a randomized, controlled trial that compared inhaled racemic adrenaline versus saline. Virus genome was identified and quantified by polymerase chain reaction analyses. Severity was assessed on the basis of the length of stay and the use of supportive care. Respiratory syncytial virus (83%) and human rhinovirus (34%) were most commonly detected. Seven other viruses were present in 8%-15% of the patients. Two or more viruses (maximum, 7) were detected in 61% of the infants. Virus type or coinfection was not associated with disease severity. A high genomic load of respiratory syncytial virus was associated with a longer length of stay and with an increased frequency of oxygen and ventilatory support use. Treatment effect of inhaled adrenaline was not modified by virus type, load or coinfection. In infants hospitalized with acute bronchiolitis, disease severity was not associated with specific viruses or the total number of viruses detected. A high RSV genomic load was associated with more-severe disease. NCT00817466 and EudraCT 2009-012667-34. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus.

PubMed

Rey-Jurado, Emma; Soto, Jorge; Gálvez, Nicolás; Kalergis, Alexis M

2017-09-02

The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

Spatiotemporal patterns of infant bronchiolitis in a Tennessee Medicaid population.

PubMed

Sloan, Chantel D; Gebretsadik, Tebeb; Wu, Pingsheng; Carroll, Kecia N; Mitchel, Edward F; Hartert, Tina V

2013-09-01

Respiratory syncytial virus (RSV) is a major cause of worldwide morbidity and mortality in infants, primarily through the induction of bronchiolitis. RSV epidemics are highly seasonal, occurring in the winter months in the northern hemisphere. Within the United States, RSV epidemic dynamics vary both spatially and temporally. This analysis employs a retrospective space–time scan statistic to locate spatiotemporal clustering of infant bronchiolitis in a very large Tennessee (TN) Medicaid cohort. We studied infants less than 6 months of age (N = 52,468 infants) who had an outpatient visit, emergency department visit, or hospitalization for bronchiolitis between 1995 and 2008. The scan statistic revealed distinctive and consistent patterns of deviation in epidemic timing. Eastern TN (Knoxville area) showed clustering in January and February, and Central TN (Nashville area) in November and December. This is likely due to local variation in geography-associated factors which should be taken into consideration in future modeling of RSV epidemics.

Bronchiolitis-associated encephalopathy in critically-ill infants: an underestimated complication?

PubMed

Antonucci, Roberto; Chiappe, Stefano; Porcella, Annalisa; Rosatelli, Daniela; Fanos, Vassilios

2010-05-01

To investigate the bronchiolitis-associated encephalopathy in critically ill infants. The records of infants with severe bronchiolitis admitted to our intensive care unit between 1991 and 2003 were reviewed. Subjects with underlying neurological disorders were excluded. Encephalopathy was defined as occurrence of seizures or at least two nonconvulsive neurologic manifestations. A semistructured telephone interview investigated long-term neurodevelopmental outcome. Twenty-one infants (11 newborns) were enrolled. All patients required oxygen supplementation and 14 required mechanical ventilation. Encephalopathy occurred in 10 infants, six of whom developed seizures. Encephalopathic infants frequently (six of nine) showed transient EEG abnormalities, and occasionally (one of nine) cranial ultrasound abnormalities. A positive respiratory syncytial virus test was found in five of nine encephalopathic infants. One encephalopathic patient died, while 20 infants clinically normalised before discharge and showed a good neurodevelopmental outcome. Acute encephalopathy was frequently observed in our patients with severe bronchiolitis. Long-term prognosis of encephalopathic infants was good.

Existence of periodic solutions in a model of respiratory syncytial virus RSV

NASA Astrophysics Data System (ADS)

Arenas, Abraham J.; González, Gilberto; Jódar, Lucas

2008-08-01

In this paper we study the existence of a positive periodic solutions for nested models of respiratory syncytial virus RSV, by using a continuation theorem based on coincidence degree theory. Conditions for the existence of periodic solutions in the model are given. Numerical simulations related to the transmission of respiratory syncytial virus in Madrid and Rio Janeiro are included.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

PubMed

Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J; McKoy, Naomi A

2013-06-05

Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 11 October 2012. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab

Autonomic dysfunction with early respiratory syncytial virus-related infection.

PubMed

Stock, Claire; Teyssier, Georges; Pichot, Vincent; Goffaux, Philippe; Barthelemy, Jean-Claude; Patural, Hugues

2010-08-25

Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (alpha LF, alpha HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group (p<0.05). RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring. Copyright 2010 Elsevier B.V. All rights reserved.

Pro-Inflammatory Cytokines in Nasopharyngeal Aspirate From Hospitalized Children With Respiratory Syncytial Virus Infection With or Without Rhinovirus Bronchiolitis, and Use of the Cytokines as Predictors of Illness Severity

PubMed Central

Díaz, Patricia V.; Valdivia, Gonzalo; Gaggero, Aldo A.; Bono, M.R.; Zepeda, Guillermo; Rivas, Mabel; Uasapud, Paola; Pinto, Ricardo A.; Boza, M. Lina; Guerrero, Julia

2015-01-01

Abstract Respiratory syncytial virus (RSV) and human rhinovirus (HRV) respiratory infection in children induce production of inflammatory interleukins (ILs) in the respiratory epithelium. As IL(s) determine the severity of illness, the purpose of this study was to identify the pro-inflammatory IL(s) that could be predictor(s) of clinical severity. One hundred and fifteen patients <2 years old with bronchiolitis due to RSV and /or HRV and 38 controls were selected from a hospital and an outpatient clinic. Clinical data of all patients were recorded. Severity was defined by the number of days with oxygen need. Nasopharyngeal aspirates (NPA) were collected to perform viral diagnosis by quantitative reverse transcription and polymerase chain reaction (qRT-PCR) and to quantify ILs: TNF-α, IL-10, IL-6, IL-1β, and IL-8, by flow cytometry. Simple and multiple regression and receiver operating characteristic (ROC) curves were used for statistical analysis. Of the patients selected 60 were single RSV, 28 RSV associated to HRV, and 27 single HRV. All patients (115) showed significantly higher IL levels when compared with controls. Levels of IL-6, IL-1β, and IL-8 detected in NPA from RSV single and associated to HRV were significantly higher than HRV infected and positively associated with days requiring O2. Levels of IL-6, IL-1β, and IL-8 detected in NPA from patients infected with RSV only or with both RSV and HRV are increased, and any of those 3 cytokines may have a predictive value for the number of days with need of supplemental oxygen. PMID:26426613

Extrapulmonary manifestations of severe respiratory syncytial virus infection – a systematic review

PubMed Central

Eisenhut, Michael

2006-01-01

Introduction Respiratory syncytial virus (RSV) bronchiolitis is the most important cause for admission to the paediatric intensive care unit in infants with lower respiratory tract infection. In recent years the importance of extrapulmonary manifestations of RSV infection has become evident. This systematic review aimed at summarizing the available evidence on manifestations of RSV infection outside the respiratory tract, their causes and the changes in clinical management required. Methods Databases searched were Medline (1950 to present), EMBASE (1974 to present), PubMed and reference lists of relevant articles. Summarized were the findings of articles reporting on manifestations of RSV infection outside the respiratory tract in patients of all age groups. Results Extrapulmonary manifestations reported in previous observational studies included cardiovascular failure with hypotension and inotrope requirements associated with myocardial damage as evident from elevated cardiac troponin levels (35–54% of ventilated infants), cardiac arrhythmias like supraventricular tachycardias and ventricular tachycardias, central apnoeas (16–21% of admissions), focal and generalized seizures, focal neurological abnormalities, hyponatraemia (33%) associated with increased antidiuretic hormone secretion, and hepatitis (46–49% of ventilated infants). RSV or its genetic material have been isolated from cerebrospinal fluid, myocardium, liver and peripheral blood. Conclusion The data summarized indicate a systemic dissemination of RSV during severe disease. Cerebral and myocardial involvement may explain the association of RSV with some cases of sudden infant death. In infants with severe RSV infection cardiac rhythm, blood pressure and serum sodium need to be monitored and supportive treatment including fluid management adjusted accordingly. PMID:16859512

[Lower lymphocyte response in severe cases of acute bronchiolitis due to respiratory syncytial virus].

PubMed

Ramos-Fernández, José Miguel; Moreno-Pérez, David; Antúnez-Fernández, Cristina; Milano-Manso, Guillermo; Cordón-Martínez, Ana María; Urda-Cardona, Antonio

2018-06-01

Acute bronchiolitis (AB) of the infant has a serious outcome in 6-16% of the hospital admitted cases. Its pathogenesis and evolution is related to the response of the T lymphocytes. The objective of the present study is to determine if the lower systemic lymphocytic response is related to a worse outcome of AB in hospitalised infants. Retrospective observational-analytical study of cases-controls nested in a cohort of patients admitted due to RSV-AB between the period from October 2010 to March 2015. Those with a full blood count in the first 48hours of respiratory distress were included. Infants with underlying disease, bacterial superinfection, and premature infants <32 weeks of gestation were excluded. The main dichotomous variable was PICU admission. Other variables were: gender, age, post-menstrual age, gestational and post-natal tobacco exposure, admission month, type of lactation, and days of onset of respiratory distress. Lymphocyte counts were categorised by quartiles. Bivariate analysis was performed with the main variable and then by logistic regression to analyse confounding factors. The study included 252 infants, of whom 6.6% (17) required PICU admission. The difference in mean±SD of lymphocytes for patients admitted to and not admitted to PICU was 4,044±1755 and 5,035±1786, respectively (Student-t test, P<.05). An association was found between PICU admission and lymphocyte count <3700/ml (Chi-squared, P=.019; OR: 3.2) and it was found to be maintained in the logistic regression, regardless of age and all other studied factors (Wald 4.191 P=.041, OR: 3.8). A relationship was found between lymphocytosis <3700/ml in the first days of respiratory distress and a worse outcome in previously healthy infants <12 months and gestational age greater than 32 weeks with RSV-AB. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

PubMed

Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J; McKoy, Naomi A

2012-02-15

Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 25 October 2011. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued

Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants

PubMed Central

Espinosa, Yazmín; San Martín, Camila; Torres, Alejandro A.; Farfán, Mauricio J.; Torres, Juan P.; Avadhanula, Vasanthi; Piedra, Pedro A.; Tapia, Lorena I.

2017-01-01

The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies. PMID:28335547

Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection.

PubMed

Xu, Mei Ling; Wi, Ga Ram; Kim, Hyoung Jin; Kim, Hong-Jin

2016-01-01

Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

The Role of Human Milk Immunomodulators in Protecting Against Viral Bronchiolitis and Development of Chronic Wheezing Illness.

PubMed

Dixon, Dani-Louise

2015-07-07

Infants who are breastfed are at an immunological advantage when compared with formula fed infants, evidenced by decreased incidence of infections and diminished propensity for long term conditions, including chronic wheeze and/or asthma. Exclusive breastfeeding reduces the duration of hospital admission, risk of respiratory failure and requirement for supplemental oxygen in infants hospitalised with bronchiolitis suggesting a potentially protective mechanism. This review examines the evidence and potential pathways for protection by immunomodulatory factors in human milk against the most common viral cause of bronchiolitis, respiratory syncytial virus (RSV), and subsequent recurrent wheeze in infants. Further investigations into the interplay between respiratory virus infections such as RSV and how they affect, and are affected by, human milk immunomodulators is necessary if we are to gain a true understanding of how breastfeeding protects many infants but not all against infections, and how this relates to long-term protection against conditions such as chronic wheezing illness or asthma.

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

PubMed Central

Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

2016-01-01

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts.

PubMed

Stittelaar, Koert J; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J B; Fraaij, Pieter L A; van Baalen, Carel A; van Kampen, Jeroen J A; van der Vries, Erhard; Osterhaus, Albert D M E; de Swart, Rik L

2016-06-14

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (10⁵ TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

PubMed Central

Larios Mora, Alejandro; Detalle, Laurent; Van Geelen, Albert; Davis, Michael S.; Stohr, Thomas; Gallup, Jack M.; Ackermann, Mark R.

2015-01-01

Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and

Potential for palivizumab interference with commercially available antibody-antigen based respiratory syncytial virus diagnostic assays.

PubMed

Deming, Damon J; Patel, Nita; McCarthy, Michael P; Mishra, Lalji; Shapiro, Alan M; Suzich, JoAnn A

2013-10-01

Palivizumab is a monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus infection in infants. The potential for palivizumab to interfere with commercially available respiratory syncytial virus diagnostic tests was demonstrated. Negative test results in palivizumab-treated subjects should be interpreted with caution and confirmed by a nucleic acid amplification-based assay.

LDH concentration in nasal-wash fluid as a biochemical predictor of bronchiolitis severity.

PubMed

Laham, Federico R; Trott, Amanda A; Bennett, Berkeley L; Kozinetz, Claudia A; Jewell, Alan M; Garofalo, Roberto P; Piedra, Pedro A

2010-02-01

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.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

PubMed

Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J

2016-07-20

Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

PubMed

Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J

2014-05-22

Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 17 March 2014. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has

Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo.

PubMed

Xu, Jiao-Jiao; Liu, Zhong; Tang, Wei; Wang, Guo-Cai; Chung, Hau Yin; Liu, Qiu-Ying; Zhuang, Ling; Li, Man-Mei; Li, Yao-Lan

2015-11-04

Human respiratory syncytial virus (RSV) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. Our previous study showed that tangeretin from Citrus reticulate possessed potent in vitro anti-RSV effects comparable to that of ribavirin. Therefore, in this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice. Moreover, a luminex assay indicated tangeretin relieved RSV-induced lung inflammation by attenuating interleukin (IL)-1β secretion. Possible anti-inflammatory mechanisms of tangeretin were preliminarily explored using a RSV-infected macrophage model. A FQ-PCR, enzyme-linked immunosorbent assay (ELISA), and luciferase assay revealed that tangeretin inhibited RSV-induced inflammation by suppressing nuclear factor-κB (NF-κB) activation. This study demonstrates that tangeretin inhibited RSV replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating RSV infections and inflammation.

Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

PubMed

Anderson, Evan J; Carbonell-Estrany, Xavier; Blanken, Maarten; Lanari, Marcello; Sheridan-Pereira, Margaret; Rodgers-Gray, Barry; Fullarton, John; Rouffiac, Elisabeth; Vo, Pamela; Notario, Gerard; Campbell, Fiona; Paes, Bosco

2017-02-01

Moderate-late preterm infants, 33-35 weeks' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants. A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants' 33-35 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. The burden of RSVH in moderate-late, 33-35 weeks' wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy.

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

PubMed

Portelli, J; Gordon, A; May, J T

1998-11-01

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice

PubMed Central

Paes, Bosco A; Mitchell, Ian; Banerji, Anna; Lanctôt, Krista L; Langley, Joanne M

2011-01-01

Respiratory syncytial virus (RSV) is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies. The present article reviews the epidemiology of RSV infection and the short- and long-term impact of disease in high-risk infants and special populations. Prevention strategies and treatment are discussed based on the existing scientific evidence, and future challenges in the management of RSV infection are addressed. PMID:21499597

Robust Cytokine and Chemokine Response in Nasopharyngeal Secretions: Association With Decreased Severity in Children With Physician Diagnosed Bronchiolitis

PubMed Central

Nicholson, Erin G.; Schlegel, Chelsea; Garofalo, Roberto P.; Mehta, Reena; Scheffler, Margaret; Mei, Minghua; Piedra, Pedro A.

2016-01-01

Background. Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis. Methods. Children <24 months old who presented to the emergency department with signs and symptoms of bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. Results. One hundred eleven children with bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] γ; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-γ, and IFN-γ–inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. Conclusions. The cytokines and chemokines significantly associated with decreased bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children. PMID:27190183

LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity

PubMed Central

Laham, Federico R.; Trott, Amanda A.; Bennett, Berkeley L.; Kozinetz, Claudia A.; Jewell, Alan M.; Garofalo, Roberto P.; Piedra, Pedro A.

2011-01-01

Objective 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. Patients and Methods 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. Results Of 101 enrolled children (median age, 5.6 months), 98 had NW specimens available. A viral etiology was found in 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=0.011). Conclusions NW LDH levels in young children with bronchiolitis varied according to viral etiology and disease severity. Values in the upper quartile were associated with ~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. PMID:20100751

Interferon lambda 1-3 expression in infants hospitalized for RSV or HRV associated bronchiolitis.

PubMed

Selvaggi, Carla; Pierangeli, Alessandra; Fabiani, Marco; Spano, Lucia; Nicolai, Ambra; Papoff, Paola; Moretti, Corrado; Midulla, Fabio; Antonelli, Guido; Scagnolari, Carolina

2014-05-01

The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. As an additional objective we sought to determine whether a different expression of IFN lambda 1-3 was associated with different harboring viruses, the clinical course of bronchiolitis or with the levels of well established IFN stimulated genes (ISGs), such as mixovirus resistance A (MxA) and ISG56. The analysis was undertaken in 118 infants with RSV or HRV bronchiolitis. Nasopharyngeal washes were collected for virological studies and molecular analysis of type III IFN responses. RSV elicited higher levels of IFN lambda subtypes when compared with HRV. A similar expression of type III IFN was found in RSVA or RSVB infected infants and in those infected with HRVA or HRVC viruses. Results also indicate that IFN lambda 1 and IFN lambda 2-3 levels were correlated with each other and with MxA and ISG56-mRNAs. In addition, a positive correlation exists between the IFN lambda1 levels and the clinical score index during RSV infection. In particular, higher IFN lambda 1 levels are associated to an increase of respiratory rate. These findings show that differences in the IFN lambda 1-3 levels in infants with RSV or HRV infections are present and that the expression of IFN lambda 1 correlates with the severity of RSV bronchiolitis. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus.

PubMed

Grover, M; Giouzeppos, O; Schnagl, R D; May, J T

1997-03-01

The effect of lactoferrin and prostaglandins E and F2 alpha on the growth of rotavirus and respiratory syncytial virus in cell culture was investigated. Lactoferrin inhibited the growth of respiratory syncytial virus at a concentration tenfold lower than that normally present in human milk. The prostaglandins had no effect on either virus growth, even at a concentration of 100-fold more than that found in human milk. Lactoferrin may have some antiviral properties in human milk in addition to its known antibacterial functions.

Oral ribavirin for respiratory syncytial virus infection after lung transplantation: Efficacy and cost-efficiency.

PubMed

Burrows, Fay S; Carlos, Lilibeth M; Benzimra, Mark; Marriott, Deborah J E; Havryk, Adrian P; Plit, Marshall L; Malouf, Monique A; Glanville, Allan R

2015-07-01

Respiratory syncytial virus (RSV) causes serious respiratory tract infections in lung transplant (LTx) recipients, is associated with development of bronchiolitis obliterans syndrome, and has no proven effective therapy. We evaluated the efficacy, safety, and cost-effectiveness of oral ribavirin for the treatment of RSV infection after LTx. Between December 2011 and May 2014, 52 LTx recipients developed 56 episodes of symptomatic RSV infection, which was diagnosed by positive RSV polymerase chain reaction on nasopharyngeal swabs. An intravenous (IV) loading dose of ribavirin (33 mg/kg) was given in 52 of 56 episodes; an equivalent oral loading dose was given in 2 episodes. Oral ribavirin (20 mg/kg/day) was given by day 2 in 53 of 56 episodes. Median duration of therapy was 8 days (range 6-31 days). Mean forced expiratory volume in 1 sec decreased from 2.38 ± 0.78 liters to 2.07 ± 0.85 liters (p < 0.001) at presentation, recovered to 2.26 ± 0.82 liters at cessation of ribavirin, and was maintained at 2.31 ± 0.81 liters within 3 months. New-onset bronchiolitis obliterans syndrome developed in 1 of 38 patients (2.6%) at 3 months. Anemia worsened in 23 episodes, and de novo anemia developed in 5 episodes. Mean hemoglobin decreased from 118 ± 16 g/liter to 113 ± 21 g/liter (p = 0.015). There were 4 late deaths. Compared with IV therapy, mean drug cost saving was US $6,035 per episode, and mean inpatient bed days was reduced by 6.7 days (p < 0.001). To our knowledge, we report the largest series of LTx recipients treated with oral ribavirin for RSV. Oral ribavirin appears to be an effective, well-tolerated alternative to IV or inhaled ribavirin; provides considerable cost savings and reduces length of hospital stay. Potential long-term benefits in preventing development of chronic lung allograft dysfunction are yet to be determined. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines.

PubMed

Kadji, Francois Marie Ngako; Okamoto, Michiko; Furuse, Yuki; Tamaki, Raita; Suzuki, Akira; Lirio, Irene; Dapat, Clyde; Malasao, Rungnapa; Saito, Mariko; Pedrera-Rico, Gay Anne Granada; Tallo, Veronica; Lupisan, Socorro; Saito, Mayuko; Oshitani, Hitoshi

2016-06-27

Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis.

PubMed

Sánchez-Solis, M; Gartner, S; Bosch-Gimenez, V; Garcia-Marcos, L

2015-01-01

Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking. A literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed. The number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077-0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086-0.182) (Q=13.9; p<0.001). Palivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Robust Cytokine and Chemokine Response in Nasopharyngeal Secretions: Association With Decreased Severity in Children With Physician Diagnosed Bronchiolitis.

PubMed

Nicholson, Erin G; Schlegel, Chelsea; Garofalo, Roberto P; Mehta, Reena; Scheffler, Margaret; Mei, Minghua; Piedra, Pedro A

2016-08-15

Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis. Children <24 months old who presented to the emergency department with signs and symptoms of bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. One hundred eleven children with bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] γ; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-γ, and IFN-γ-inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. The cytokines and chemokines significantly associated with decreased bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Respiratory syncytial virus serological reagents. 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480...

21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Respiratory syncytial virus serological reagents. 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480...

21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Respiratory syncytial virus serological reagents. 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480...

21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Respiratory syncytial virus serological reagents. 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480...

21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Respiratory syncytial virus serological reagents. 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480...

Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity.

PubMed

Mehta, Reena; Scheffler, Margaret; Tapia, Lorena; Aideyan, Letisha; Patel, Kirtida D; Jewell, Alan M; Avadhanula, Vasanthi; Mei, Minghua; Garofalo, Roberto P; Piedra, Pedro A

2014-11-01

Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Respiratory syncytial virus tracking using internet search engine data.

PubMed

Oren, Eyal; Frere, Justin; Yom-Tov, Eran; Yom-Tov, Elad

2018-04-03

Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in children less than 1 year of age in the United States. Internet search engine queries may provide high resolution temporal and spatial data to estimate and predict disease activity. After filtering an initial list of 613 symptoms using high-resolution Bing search logs, we used Google Trends data between 2004 and 2016 for a smaller list of 50 terms to build predictive models of RSV incidence for five states where long-term surveillance data was available. We then used domain adaptation to model RSV incidence for the 45 remaining US states. Surveillance data sources (hospitalization and laboratory reports) were highly correlated, as were laboratory reports with search engine data. The four terms which were most often statistically significantly correlated as time series with the surveillance data in the five state models were RSV, flu, pneumonia, and bronchiolitis. Using our models, we tracked the spread of RSV by observing the time of peak use of the search term in different states. In general, the RSV peak moved from south-east (Florida) to the north-west US. Our study represents the first time that RSV has been tracked using Internet data results and highlights successful use of search filters and domain adaptation techniques, using data at multiple resolutions. Our approach may assist in identifying spread of both local and more widespread RSV transmission and may be applicable to other seasonal conditions where comprehensive epidemiological data is difficult to collect or obtain.

Animal models of respiratory syncytial virus infection and disease

USDA-ARS?s Scientific Manuscript database

The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the ...

Simultaneous influenza and respiratory syncytial virus infection in human respiratory tract

NASA Astrophysics Data System (ADS)

Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

2015-03-01

Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is not uncommon in hospitalized patients, although it is not clear whether these infections are more or less severe than single infections. We use mathematical models to study the dynamics of simultaneous influenza (flu) and respiratory syncytial virus (RSV) infection, two of the more common respiratory viruses, in an effort to understand simultaneous infections. We examine the roles of initial viral inoculum, relative starting time, and cell regeneration on the severity of the infection. We also study the effect of antiviral treatment on the course of the infection. This study shows that, unless treated with antivirals, flu always takes over the infection no matter how small the initial dose and how delayed it starts with respect to RSV.

Nasopharyngeal bacterial burden and antibiotics: Influence on inflammatory markers and disease severity in infants with respiratory syncytial virus bronchiolitis.

PubMed

Suárez-Arrabal, M Carmen; Mella, Cesar; Lopez, Santiago M; Brown, Nicole V; Hall, Mark W; Hammond, Sue; Shiels, William; Groner, Judith; Marcon, Mario; Ramilo, Octavio; Mejias, Asuncion

2015-10-01

Animal studies suggest that RSV increases nasopharyngeal (NP) bacterial colonization facilitating bacterial infections. We investigated the influence of antibiotic treatment and colonization with potentially pathogenic bacteria on inflammatory markers and disease severity in RSV-infected in infants. Healthy young infants hospitalized with RSV bronchiolitis (n = 136) and age-matched healthy controls (n = 23) were enrolled and NP samples cultured for potentially pathogenic bacteria including: Gram-positive bacteria (GPB): Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic Streptococcus; and Gram-negative bacteria (GNB): Moraxella catarrhalis and Haemophilus influenzae. Clinical parameters and plasma IL-8, IL-6 and TNF-α concentrations were compared according to the bacterial class and antibiotic treatment. Antibiotic treatment decreased by 10-fold NP bacterial recovery. Eighty-one percent of RSV infants who did not receive antibiotics before sample collection were colonized with pathogenic bacteria. Overall, GNB were identified in 21% of patients versus 4% of controls who were mostly colonized with GPB. Additionally, in RSV patients NP white blood cell counts (p = 0.026), and blood neutrophils (p = 0.02) were higher in those colonized with potentially pathogenic bacteria versus respiratory flora. RSV patients colonized with GNB had higher plasma IL-8 (p = 0.01) and IL-6 (p < 0.01) concentrations than controls, and required longer duration of oxygen (p = 0.049). Infants with RSV bronchiolitis colonized with potentially pathogenic bacteria had increased numbers of mucosal and systemic inflammatory cells. Specifically, colonization with GNB was associated with higher concentrations of proinflammatory cytokines and a trend towards increased disease severity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Better newborn vitamin D status lowers RSV-associated bronchiolitis in infants.

PubMed

Maxwell, Christy S; Carbone, Elena T; Wood, Richard J

2012-09-01

Each year 1.5 million children under the age of 5 years die from pneumonia. In the United States, respiratory syncytial virus (RSV) is the number one cause of bronchiolitis and pneumonia in children under 1 year of age. Low serum 25(OH)D is associated with an increased risk of lower respiratory tract infections (LRTI). Two recent studies have provided important information concerning the association between cord blood 25(OH)D and subsequent risk of developing respiratory infection in very young children. These findings support the need in future studies to determine the extent to which an intervention to change the vitamin D status of mothers during pregnancy can reduce the risk of RSV-associated LRTI in their offspring. An answer to this question would have significant worldwide public health importance given the high prevalence of low vitamin D status worldwide and the high mortality burden accompanying infectious lung diseases in young children. © 2012 International Life Sciences Institute.

Respiratory outcomes, utilization and costs 12 months following a respiratory syncytial virus diagnosis among commercially insured late-preterm infants.

PubMed

Palmer, Liisa; Hall, Caroline B; Katkin, Julie P; Shi, Nianwen; Masaquel, Anthony S; McLaurin, Kimmie K; Mahadevia, Parthiv J

2011-02-01

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). 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. 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). 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.

RSV antibody test

MedlinePlus

Respiratory syncytial virus antibody test; RSV serology; Bronchiolitis - RSV test ... Crowe JE. Respiratory syncytial virus. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ...

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

PubMed Central

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

T helper 1 background protects against airway hyperresponsiveness and inflammation in guinea pigs with persistent respiratory syncytial virus infection.

PubMed

Sutton, Troy C; Tayyari, Farnoosh; Khan, M Aatif; Manson, Heather E; Hegele, Richard G

2007-05-01

A family history of allergy has been implicated in children who develop post-bronchiolitis wheezing and asthma. In a guinea pig model of respiratory syncytial virus (RSV) lung infection, we evaluated the role of host Th1 background (either genetic or induced) on the development of a persistent infection, nonspecific airway hyperresponsiveness (AHR) and airway inflammation. Allergy resistant/T helper 1 (Th1)-skewed strain 2 guinea pigs (STR2) and cytosine phosphate guanine oligodeoxynucleotides (CpG-ODN) (Th1 stimuli) pretreated Cam Hartley guinea pigs (CH) were inoculated with RSV and compared with virus-inoculated allergy-susceptible/Th2-skewed CHs and to sham-inoculated STR2 and CH, 60 d post-inoculation. We measured titers of intrapulmonary RSV, lung interferon (IFN)-gamma and interleukin (IL)-5 mRNA expression, AHR and airway T cells and eosinophils. All virus-inoculated groups of animals showed evidence of persistent RSV lung infection; however, Th2-skewed guinea pigs had virus-associated AHR and significantly greater levels of airway T cells and eosinophils. In conclusion, RSV can establish persistent infection of the guinea pig lung regardless of host Th1/Th2 background; however; a host Th1 background limits the extent of virus-associated AHR and airway inflammation. Heterogeneity in virus-host interactions may be relevant to understanding why some children hospitalized for RSV bronchiolitis go on to develop recurrent wheezing/asthma symptoms.

Respiratory syncytial virus infection in cattle.

PubMed

Sacco, R E; McGill, J L; Pillatzki, A E; Palmer, M V; Ackermann, M R

2014-03-01

Bovine respiratory syncytial virus (RSV) is a cause of respiratory disease in cattle worldwide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV infection can predispose calves to secondary bacterial infection by organisms such as Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Even in cases where animals do not succumb to bovine respiratory disease complex, there can be long-term losses in production performance. This includes reductions in feed efficiency and rate of gain in the feedlot, as well as reproductive performance, milk production, and longevity in the breeding herd. As a result, economic costs to the cattle industry from bovine respiratory disease have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Human and bovine RSV are closely related viruses with similarities in histopathologic lesions and mechanisms of immune modulation induced following infection. Therefore, where appropriate, we provide comparisons between RSV infections in humans and cattle. This review article discusses key aspects of RSV infection of cattle, including epidemiology and strain variability, clinical signs and diagnosis, experimental infection, gross and microscopic lesions, innate and adaptive immune responses, and vaccination strategies.

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

PubMed

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007-2012.

PubMed

Reeves, Rachel Melanie; Hardelid, Pia; Gilbert, Ruth; Warburton, Fiona; Ellis, Joanna; Pebody, Richard G

2017-03-01

Respiratory syncytial virus (RSV) is a leading cause of hospital admission in young children. With several RSV vaccines candidates undergoing clinical trials, recent estimates of RSV burden are required to provide a baseline for vaccine impact studies. To estimate the number of RSV-associated hospital admissions in children aged <5 years in England over a 5-year period from 2007 using ecological time series modelling of national hospital administrative data. Multiple linear regression modelling of weekly time series of laboratory surveillance data and Hospital Episode Statistics (HES) data was used to estimate the number of hospital admissions due to major respiratory pathogens including RSV in children <5 years of age in England from mid-2007 to mid-2012, stratified by age group (<6 months, 6-11 months, 1-4 years) and primary diagnosis: bronchiolitis, pneumonia, unspecified lower respiratory tract infection (LRTI), bronchitis and upper respiratory tract infection (URTI). On average, 33 561 (95% confidence interval 30 429-38 489) RSV-associated hospital admissions in children <5 years of age occurred annually from 2007 to 2012. Average annual admission rates were 35.1 (95% CI: 32.9-38.9) per 1000 children aged <1 year and 5.31 (95% CI: 4.5-6.6) per 1000 children aged 1-4 years. About 84% (95% CI: 81-91%) of RSV-associated admissions were for LRTI. The diagnosis-specific burden of RSV-associated admissions differed significantly by age group. RSV remains a significant cause of hospital admissions in young children in England. Individual-level analysis of RSV-associated admissions is required to fully describe the burden by age and risk group and identify optimal prevention strategies. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity

PubMed Central

Mehta, Reena; Scheffler, Margaret; Tapia, Lorena; Aideyan, Letisha; Patel, Kirtida D; Jewell, Alan M; Avadhanula, Vasanthi; Mei, Minghua; Garofalo, Roberto P; Piedra, Pedro A

2014-01-01

Background Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. Objective To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. Methods Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. Results A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. Conclusions NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center. PMID:25132512

Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf

USDA-ARS?s Scientific Manuscript database

Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to R...

Distinguishing between respiratory syncytial virus subgroups by protein profile analysis.

PubMed Central

Walpita, P; Mufson, M A; Stanek, R J; Pfeifer, D; Connor, J D

1992-01-01

We subgrouped 75 strains of respiratory syncytial virus by a protein profile method (PPM) which relies on different mobilities of the phosphoprotein in one-dimensional polyacrylamide gel electrophoresis and does not require monoclonal antibodies. When compared with enzyme immunoassay, PPM correctly subgrouped 54 of 56 subgroup A and all 19 subgroup B strains. Images PMID:1572961

The impact of temperature and relative humidity on spatiotemporal patterns of infant bronchiolitis epidemics in the contiguous United States.

PubMed

Sloan, Chantel; Heaton, Matthew; Kang, Sorah; Berrett, Candace; Wu, Pingsheng; Gebretsadik, Tebeb; Sicignano, Nicholas; Evans, Amber; Lee, Rees; Hartert, Tina

2017-05-01

Infant bronchiolitis is primarily due to infection by respiratory syncytial virus (RSV), which is highly seasonal. The goal of the study is to understand how circulation of RSV is impacted by fluctuations in temperature and humidity in order to inform prevention efforts. Using data from the Military Health System (MHS) Data Repository (MDR), we calculated rates of infant bronchiolitis for the contiguous US from July 2004 to June 2013. Monthly temperature and relative humidity were extracted from the National Climate Data Center. Using a spatiotemporal generalized linear model for binomial data, we estimated bronchiolitis rates and the effects of temperature and relative humidity while allowing them to vary over location and time. Our results indicate a seasonal pattern that begins in the Southeast during November or December, then spreading in a Northwest direction. The relationships of temperature and humidity were spatially heterogeneous, and we find that climate can partially account for early onset or longer epidemic duration. Small changes in climate may be associated with larger fluctuations in epidemic duration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of monoclonal antibodies that detect conserved proteins from Respiratory Syncytial Virus, Metapneumovirus and Adenovirus in human samples.

PubMed

González, Liliana A; Vázquez, Yaneisi; Mora, Jorge E; Palavecino, Christian E; Bertrand, Pablo; Ferrés, Marcela; Contreras, Ana M; Beckhaus, Andrea A; Riedel, Claudia A; Bueno, Susan M

2018-04-01

Human Respiratory Syncytial Virus (hRSV), human Metapneumovirus (hMPV) and Adenovirus (ADV), are three of the most prevalent viruses responsible for pneumonia and bronchiolitis in children and elderly worldwide, accounting for a high number of hospitalizations annually. Diagnosis of these viruses is required to take clinical actions that allow an appropriate patient management. Thereby, new strategies to design fast diagnostic methods are highly required. In the present work, six monoclonal antibodies (mAbs, two for each virus) specific for conserved proteins from hRSV, hMPV and ADV were generated and evaluated through different immunological techniques, based on detection of purified protein, viral particles and human samples. In vitro evaluation of these antibodies showed higher specificity and sensitivity than commercial antibodies tested in this study. These antibodies were used to design a sandwich ELISA tests that allowed the detection of hRSV, hMPV, and ADV in human nasopharyngeal swabs. We observed that hRSV and ADV were detected with sensitivity and specificity equivalent to a current Direct Fluorescence Assay (DFA) methodology. However, hMPV was detected with more sensitivity than DFA. Our data suggest that these new mAbs can efficiently identify infected samples and discriminate from patients infected with other respiratory pathogens. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The modified respiratory index score (RIS) guides resource allocation in acute bronchiolitis.

PubMed

Chong, Shu-Ling; Teoh, Oon Hoe; Nadkarni, Nivedita; Yeo, Joo Guan; Lwin, Zaw; Ong, Yong-Kwang Gene; Lee, Jan Hau

2017-07-01

Bronchiolitis is a common disease in early childhood with increasing healthcare utilization. We aim to study how well a simple and improved respiratory score (the modified Respiratory Index Score [RIS]) would perform when predicting for a warranted admission. This is an observational prospective study, from June 2015 to December 2015 in a paediatric emergency department (ED) of a large tertiary hospital in Singapore. We included children aged less than 2 years old, presenting with typical symptoms and signs of bronchiolitis but excluded children with four or more previous wheezes, a gestation of <35 weeks, and known cardiopulmonary disease. We also performed a sensitivity analysis for children presenting with their first wheeze. We defined a warranted admission as a composite of: The need for airway intervention, intravenous hydration, and a hospital stay of 2 days or more. Among 1,818 patients, the median age was 10.8 months (IQR 7.2-15.9). The median modified RIS score was 4.0 (IQR 3.0-5.0). A total of 19 (1.0%) children required respiratory support, 101 (5.6%) received intravenous hydration, and 571 (31.4%) required a hospital stay of 2 days or more. After adjusting for age and duration of illness, a modified RIS score of >4 predicted significantly for a warranted admission (adjusted Odds Ratio: 3.28, 95% confidence interval: 2.62-4.12). The association remained significant among children presenting with their first wheeze. This simple respiratory tool predicts for the need for respiratory support, intravenous hydration, and a significant hospital stay of 2 days or more. Pediatr Pulmonol. 2017; 52:954-961. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Respiratory syncytial virus seasonality in southeast Florida: results from three area hospitals caring for children.

PubMed

Light, Michael

2007-11-01

Southeast Florida generally experiences longer seasonal epidemics of respiratory syncytial virus (RSV) than other parts of the country. In this report, the primary objective was to more accurately define the onset, peak, and duration of the RSV season in Southeast Florida. The results obtained for this region were also compared with those reported for the state and for the nation. Seasonal patterns for RSV in Southeast Florida were analyzed based on the total number of RSV tests performed, number of positive tests, and percent of positive tests in children presenting with bronchiolitis to 3 emergency departments from January 2003 through December 2006. RSV was detected by rapid diagnostic testing and considered to be present at epidemic levels when at least 10% of performed tests were positive during a given month. During the entire 12 months of 2003 and 2006, RSV was detected above epidemic levels. The RSV-detection test positivity rate was less than 10% in only 6 months of 48 total months of observation, but during the months that were below epidemic threshold, RSV was still frequently identified. RSV activity increased during July, peaked during October, and waned during the spring months. These findings were nearly identical to those recently reported in other studies, confirming that RSV circulated at epidemic levels in Southeast Florida during most of the 4-year observation period and remained a significant cause of respiratory disease and hospitalization throughout the year. Strategies for RSV prophylaxis in at-risk children in South Florida should consider results of local RSV test detection.

[THE COMPARATIVE ANALYSIS OF EFFECTIVENESS OF QUICK TESTS IN DIAGNOSTIC OF INFLUENZA AND RESPIRATORY SYNCYTIAL VIRAL INFECTION IN CHILDREN].

PubMed

Petrova, E R; Sukhovetskaia, V P; Pisareva, M M; Maiorova, V G; Sverlova, M V; Danilenko, D M; Petrova, P A; Krivitskaia, V Z; Sominina, A A

2015-11-01

The analysis was implemented concerning diagnostic parameters of commercial quick tests (immune chromatographic tests BinaxNOW Influenza A&B and BinaxNow RSV Alere, Scarborough Inc., USA) under detection of antigens of influenza virus A and respiratory syncytial virus in clinical materials. The polymerase chain reaction in real-time and isolation ofviruses in cell cultures. The analysis of naso-pharyngeal smears from 116 children demonstrated that sensitivity and specifcity of detection of influenza virus A using device mariPOC in comparison with polymerase chain reaction made up to 93.8% and 99.0% correspondingly at total concordance of results of both techniques as 98.3%. At diagnosing of respiratory syncytial virus using device mariPOC parameters made up to 77.3%, 98.9% and 862% as compared with polymerase chain reaction. The sensitivity, specificity and total concordance of results of immune chromatographic tests BinaxNOW in comparison ofpolymerase chain reaction made up to 86.7%, 100% and 96.2% correspondingly at detection of influenza virus A and 80.9%, 97.4% and 91.6% correspondingly at detection of respiratory syncytial virus. In comparison with isolation technique in cell cultures sensitivity of system mariPOC and immune chromatographic tests proved to be in 1.3-1.4 times higher at detection of influenza virus A and in 1.7-2 times higher in case of isolation of respiratory syncytial virus. There is no statistically significant differences between diagnostic parameters received for mariPOC and immune chromatographic tests at diagnosing influenza virus A and respiratory syncytial viral infection.

Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis.

PubMed

Kerrin, Aoife; Fitch, Paul; Errington, Claire; Kerr, Dennis; Waxman, Liz; Riding, Kay; McCormack, Jon; Mehendele, Felicity; McSorley, Henry; MacKenzie, Karen; Wronski, Sabine; Braun, Armin; Levin, Richard; Theilen, Ulf; Schwarze, Jürgen

2017-07-01

The pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in infants remains poorly understood. Mouse models implicate pulmonary T cells in the development of RSV disease. T cell responses are initiated by dendritic cells (DCs), which accumulate in lungs of RSV-infected mice. In infants with RSV bronchiolitis, previous reports have shown that DCs are mobilised to the nasal mucosa, but data on lower airway DC responses are lacking. To determine the presence and phenotype of DCs and associated immune cells in bronchoalveolar lavage (BAL) and peripheral blood samples from infants with RSV bronchiolitis. Infants intubated and ventilated due to severe RSV bronchiolitis or for planned surgery (controls with healthy lungs) underwent non-bronchoscopic BAL. Immune cells in BAL and blood samples were characterised by flow cytometry and cytokines measured by Human V-Plex Pro-inflammatory Panel 1 MSD kit. In RSV cases, BAL conventional DCs (cDCs), NK T cells, NK cells and pro-inflammatory cytokines accumulated, plasmacytoid DCs (pDCs) and T cells were present, and blood cDCs increased activation marker expression. When stratifying RSV cases by risk group, preterm and older (≥4 months) infants had fewer BAL pDCs than term born and younger (<4 months) infants, respectively. cDCs accumulate in the lower airways during RSV bronchiolitis, are activated systemically and may, through activation of T cells, NK T cells and NK cells, contribute to RSV-induced inflammation and disease. In addition, the small population of airway pDCs in preterm and older infants may reveal a distinct endotype of RSV bronchiolitis with weak antiviral pDC responses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Structural basis of respiratory syncytial virus neutralization by motavizumab

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLellan, Jason S.; Chen, Man; Kim, Albert

2010-04-13

Motavizumab is {approx}tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure.

Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool.

PubMed

Mesquita, Flávio da Silva; Oliveira, Danielle Bruna Leal de; Crema, Daniela; Pinez, Célia Miranda Nunes; Colmanetti, Thaís Cristina; Thomazelli, Luciano Matsumia; Gilio, Alfredo Elias; Vieira, Sandra Elisabeth; Martinez, Marina Baquerizo; Botosso, Viviane Fongaro; Durigon, Edison Luiz

The aim of this study was to evaluate the QuickVue ® RSV Test Kit (QUIDEL Corp, CA, USA) as a screening tool for respiratory syncytial virus in children with acute respiratory disease in comparison with the indirect immunofluorescence assay as gold standard. In Brazil, rapid antigen detection tests for respiratory syncytial virus are not routinely utilized as a diagnostic tool, except for the diagnosis of dengue and influenza. The authors retrospectively analyzed 486 nasopharyngeal aspirate samples from children under age 5 with acute respiratory infection, between December 2013 and August 2014, the samples were analyzed by indirect immunofluorescence assay and QuickVue ® RSV Test kit. Samples with discordant results were analyzed by real time PCR and nucleotide sequencing. From 313 positive samples by immunofluorescence assays, 282 (90%) were also positive by the rapid antigen detection test, two were positive only by rapid antigen detection test, 33 were positive only by immunofluorescence assays, and 171 were positive by both methods. The 35 samples with discordant results were analyzed by real time PCR; the two samples positive only by rapid antigen detection test and the five positive only by immunofluorescence assays were also positive by real time PCR. There was no relation between the negativity by QuickVue ® RSV Test and viral load or specific strain. The QuickVue ® RSV Test showed sensitivity of 90%, specificity of 98.8%, predictive positive value of 99.3%, and negative predictive value of 94.6%, with accuracy of 93.2% and agreement κ index of 0.85 in comparison to immunofluorescence assay. This study demonstrated that the QuickVue ® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanson, Kurt A.; Settembre, Ethan C.; Shaw, Christine A.

2012-02-07

Respiratory syncytial virus (RSV), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals.more » The 3.2-{angstrom} X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens.« less

[Respiratory infections, Down's syndrome and congenital heart disease: the CIVIC 21 study].

PubMed

Medrano López, C; García-Guereta Silva, L; Lirio Casero, J; García Pérez, J

2009-07-01

We compare hospitalisation rates for acute respiratory tract infection in children younger than 24 months with significant congenital heart disease without Down's syndrome with those with Down's syndrome with or without congenital heart disease. This was an epidemiological, multicentre (53 Spanish hospitals), observational and prospective study, from October 2006 to April 2007. A total of 1085 patients were followed-up, of which 806 did not have Down's syndrome and 279 with Down's syndrome: 135 with significant, 38 with non significant and 105 without congenital heart disease. A total of 147 patients (13.1%; 95% CI, 11.2-15.2%) required hospitalisation due to respiratory infection. Rates in patients without and with Down's syndrome were 11% vs 19.1%. In the Down's group, 26.3% had no significant, a 23% had significant and 11.4% had no congenital heart disease. The main diagnosis was bronchiolitis (59.4%). An infectious agent was found in 36.2% cases. The specific admission rate due to respiratory syncytial virus was 4.4%, with differences in children without vs with Down's syndrome (3.2% vs 7.8%). In the Down's patients we found rates of 15.8%, 9.3% and 3% in the non-significant, significant and no congenital heart disease. Immunoprophylaxis against respiratory syncytial virus rates were 83.4% vs 39.9% in no Down's versus Down's syndrome patients. No differences were found in hospital stay or the severity. Hospital admission rates due to respiratory infection, and specifically respiratory syncytial virus, were higher in the Down's patients, particularly in the group with no significant congenital heart disease and low immunoprophylaxis against respiratory syncytial virus.

The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P.

PubMed

Tripp, Ralph A; Dakhama, Azzeddine; Jones, Les P; Barskey, Albert; Gelfand, Erwin W; Anderson, Larry J

2003-06-01

Respiratory syncytial virus (RSV) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. We show that RSV G glycoprotein reduces respiratory rates associated with the induction of substance P (SP) and G glycoprotein-CX3CR1 interaction, an effect that is inhibited by treatment with anti-G glycoprotein, anti-SP, or anti-CX3CR1 monoclonal antibodies. These data suggest new approaches for treating some aspects of RSV disease.

The G Glycoprotein of Respiratory Syncytial Virus Depresses Respiratory Rates through the CX3C Motif and Substance P

PubMed Central

Tripp, Ralph A.; Dakhama, Azzeddine; Jones, Les P.; Barskey, Albert; Gelfand, Erwin W.; Anderson, Larry J.

2003-01-01

Respiratory syncytial virus (RSV) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. We show that RSV G glycoprotein reduces respiratory rates associated with the induction of substance P (SP) and G glycoprotein-CX3CR1 interaction, an effect that is inhibited by treatment with anti-G glycoprotein, anti-SP, or anti-CX3CR1 monoclonal antibodies. These data suggest new approaches for treating some aspects of RSV disease. PMID:12743318

Genetic variability of respiratory syncytial virus A in hospitalized children in the last five consecutive winter seasons in Central Spain.

PubMed

Calderón, Ana; Pozo, Francisco; Calvo, Cristina; García-García, Mluz; González-Esguevillas, Mónica; Molinero, Mar; Casas, Inmaculada

2017-05-01

Human respiratory syncytial virus group A (RSV-A) was detected in symptomatic hospital attended children in Central Spain for a continuous time period, September 2010 to April 2015. In order to accurately describe the epidemiology of this virus, the genetic diversity of the complete G gene and the clinical manifestations observed were jointly analyzed. Out of 3,011 respiratory specimens taken from 2,308 children, 640 were positive to RSV (21.3%) and 405 were RSV-A (63.2%). Complete G gene sequences of 166 randomly selected RSV-A virus identified NA1 and ON1 genotypes. In 2011-2012, ON1 emerged sporadically and become dominant in 2012-2013 with 38 cases (70%). In 2014-2015, all the 44 sequences contained the 72-nt duplication (100%). Clinical diagnosis of children with ON1 genotype were bronchiolitis in 55 (62.5%), recurrent wheezing or asthma exacerbations in 22 (25%), laryngotracheobronchitis in 3 (3.4%), and upper respiratory tract infections in eight. Results showed replacement and substitution of circulating NA1 genotype with the new ON1 genotype. Nevertheless, at this stage, none of the RSV-A genotypes identified have resulted in significant clinical differences. The amino acid composition of the complete G gene ON1 sequences demonstrated an accumulation of single changes not related with different clinical presentation. J. Med. Virol. 89:767-774, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia ...

Viral bronchiolitis.

PubMed

Florin, Todd A; Plint, Amy C; Zorc, Joseph J

2017-01-14

Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in...

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

PubMed Central

Liang, Bo; Surman, Sonja; Amaro-Carambot, Emerito; Kabatova, Barbora; Mackow, Natalie; Lingemann, Matthias; Yang, Lijuan; McLellan, Jason S.; Graham, Barney S.; Kwong, Peter D.; Schaap-Nutt, Anne; Collins, Peter L.

2015-01-01

ABSTRACT Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. IMPORTANCE Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F

Respiratory Syncytial Virus Isolation by Combined Continuous Flow-Isopycnic Banding Centrifugation

PubMed Central

Cline, G. B.; Coates, Helen; Anderson, N. G.; Chanock, R. M.; Harris, W. W.

1967-01-01

A new zonal centrifuge rotor (B-IX) which combines continuous sample flow centrifugation with isopycnic banding has been used to isolate and concentrate respiratory syncytial virus from liter volumes of culture fluid. This isolation technique utilizes a sucrose density gradient to trap and isopycnically band the virus particles, and permits recovery of the particles from the rotor in an unaggregated condition. PMID:5621468

New respiratory virus (chicken pox, influenza and respiratory syncytial virus) vaccines: efficacy, necessity and policy for the tropical world at present.

PubMed

Wiwanitkit, Viroj

2009-09-01

Several respiratory viruses are documented in medicine. Several infectious diseases due to these viruses are current global public health problems. Prevention of respiratory viral infections becomes the focus of the public health ministries of many tropical countries. Presently, there are many new vaccines for respiratory viruses. These vaccines include chicken pox vaccine, influenza vaccine and respiratory syncytial virus vaccine. In this article, the author will briefly discuss on these quoted vaccines focusing on efficacy, necessity and policy for tropical world at present.

Molecular Evolution of Respiratory Syncytial Virus Fusion Gene, Canada, 2006–2010

PubMed Central

Papenburg, Jesse; Carbonneau, Julie; Hamelin, Marie-Ève; Isabel, Sandra; Bouhy, Xavier; Ohoumanne, Najwa; Déry, Pierre; Paes, Bosco A.; Corbeil, Jacques; Bergeron, Michel G.; De Serres, Gaston

2012-01-01

To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSV-positive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006–2010. Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients. PMID:22264682

Efficacy of a mucosal, polyanhydride nanovaccine for use against respiratory syncytial virus infection in the neonatal calf

USDA-ARS?s Scientific Manuscript database

Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to R...

Impact of a bronchiolitis guideline on ED resource use and cost: a segmented time-series analysis.

PubMed

Akenroye, Ayobami T; Baskin, Marc N; Samnaliev, Mihail; Stack, Anne M

2014-01-01

Bronchiolitis is a major cause of infant morbidity and contributes to millions of dollars in health care costs. Care guidelines may cut costs by reducing unnecessary resource utilization. Through the implementation of a guideline, we sought to reduce unnecessary resource utilization and improve the value of care provided to infants with bronchiolitis in a pediatric emergency department (ED). We conducted an interrupted time series that examined ED visits of 2929 patients with bronchiolitis, aged 1 to 12 months old, seen between November 2007 and April 2013. Outcomes were proportion having a chest radiograph (CXR), respiratory syncytial virus (RSV) testing, albuterol or antibiotic administration, and the total cost of care. Balancing measures included admission rate, returns to the ED resulting in admission within 72 hours of discharge, and ED length of stay (LOS). There were no significant preexisting trends in the outcomes. After guideline implementation, there was an absolute reduction of 23% in CXR (95% confidence interval [CI]: 11% to 34%), 11% in RSV testing (95% CI: 6% to 17%), 7% in albuterol use (95% CI: 0.2% to 13%), and 41 minutes in ED LOS (95% CI: 16 to 65 minutes). Mean cost per patient was reduced by $197 (95% CI: $136 to $259). Total cost savings was $196,409 (95% CI: $135,592 to $258,223) over the 2 bronchiolitis seasons after guideline implementation. There were no significant differences in antibiotic use, admission rates, or returns resulting in admission within 72 hours of discharge. A bronchiolitis guideline was associated with reductions in CXR, RSV testing, albuterol use, ED LOS, and total costs in a pediatric ED.

Clinical experience with respiratory syncytial virus vaccines.

PubMed

Piedra, Pedro A

2003-02-01

Respiratory syncytial virus (RSV) infection is at times associated with life-threatening lower respiratory tract illness in infancy. Severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. Severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. However, RSV causes respiratory infections in all age groups. Indeed it is now recognized that RSV disease is responsible for significant morbidity and mortality in the geriatric population. RSV infection remains difficult to treat, and prevention is a worldwide goal. For this reason there has been an intensive effort to develop an effective and safe RSV vaccine. Initial infection with RSV affords limited protection to reinfection, yet repeated episodes decrease the risk for lower respiratory tract illness. In the 20 years from 1960 to 1980, trials of several candidate RSV vaccines failed to attain the desired safety and protection against natural infection. Some vaccine types either failed to elicit immunogenicity, as with the live subcutaneous vaccine, or resulted in exaggerated disease on natural exposure to the virus, as with the formalin-inactivated (FI) type. Currently vaccine candidates are being developed based on the molecular virology of RSV. Recent formulations of candidate RSV vaccines have focused on subunit vaccines [such as purified fusion protein (PFP)], subunit vaccines combined with nonspecific immune activating adjuvants, live attenuated vaccines (including cold passaged, temperature-sensitive or cpts mutants), genetically engineered live attenuated vaccines and polypeptide vaccines.

[Infantile meningitis caused by respiratory syncytial virus].

PubMed

Shirota, Go; Morozumi, Miyuki; Ubukata, Kimiko; Shiro, Hiroyuki

2011-11-01

Respiratory syncytial (RS) virus commonly causes infantile respiratory tract infection causing significant morbidity and mortality, but rarely meningitis. We report a case of meningitis caused by RS virus subgroup B in a 56-day-old boy admitted for high fever who underwent blood examination and lumbar puncture. Empirical chemotherapy was started with intravenous ampicillin, gentamicin, and cefotaxime based on laboratory data on CSF cells (84/microL) and serum CRP (13.8mg/dL) data. RS virus subgroup B was only detected using real-time PCR comprehensive reverse transcription from the first CSF, but no bacterial gene was detected. No bacteria grew from his CSF, urine, or blood. Fever and serum CRP dropped in a few days. He had neither seizures nor disturbance of consciousness and was discharged on day 11 after admission. No evidence of encephalopathy was detected in brain MRI or electroencephalography. RS virus rarely causes meningitis, but a percentage of RS-virus-infected infants exhibit symptoms such as seizure and disturbance of consciousness. We should recognize that the RS virus may cause neurological complications associated with high morbidity and mortality.

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate.

PubMed

Liang, Bo; Surman, Sonja; Amaro-Carambot, Emerito; Kabatova, Barbora; Mackow, Natalie; Lingemann, Matthias; Yang, Lijuan; McLellan, Jason S; Graham, Barney S; Kwong, Peter D; Schaap-Nutt, Anne; Collins, Peter L; Munir, Shirin

2015-09-01

Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we

CPAP and High-Flow Nasal Cannula Oxygen in Bronchiolitis.

PubMed

Sinha, Ian P; McBride, Antonia K S; Smith, Rachel; Fernandes, Ricardo M

2015-09-01

Severe respiratory failure develops in some infants with bronchiolitis because of a complex pathophysiologic process involving increased airways resistance, alveolar atelectasis, muscle fatigue, and hypoxemia due to mismatch between ventilation and perfusion. Nasal CPAP and high-flow nasal cannula (HFNC) oxygen may improve the work of breathing and oxygenation. Although the mechanisms behind these noninvasive modalities of respiratory support are not well understood, they may help infants by way of distending pressure and delivery of high concentrations of warmed and humidified oxygen. Observational studies of varying quality have suggested that CPAP and HFNC may confer direct physiologic benefits to infants with bronchiolitis and that their use has reduced the need for intubation. No trials to our knowledge, however, have compared CPAP with HFNC in bronchiolitis. Two randomized trials compared CPAP with oxygen delivered by low-flow nasal cannula or face mask and found some improvements in blood gas results and some physiologic parameters, but these trials were unable to demonstrate a reduction in the need for intubation. Two trials evaluated HFNC in bronchiolitis (one comparing it with headbox oxygen, the other with nebulized hypertonic saline), with the results not seeming to suggest important clinical or physiologic benefits. In this article, we review the pathophysiology of respiratory failure in bronchiolitis, discuss these trials in detail, and consider how future research studies may be designed to best evaluate CPAP and HFNC in bronchiolitis.

Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to be...

Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

PubMed

Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

2018-01-01

To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

PubMed

Rubach, M P; Pavlisko, E N; Perfect, J R

2013-08-01

We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

Respiratory Syncytial Virus Seasonality - United States, 2014-2017.

PubMed

Rose, Erica Billig; Wheatley, Alexandra; Langley, Gayle; Gerber, Susan; Haynes, Amber

2018-01-19

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide (1-3). In the United States, RSV infection results in >57,000 hospitalizations and 2 million outpatient visits each year among children aged <5 years (3). Recent studies have highlighted the importance of RSV in adults as well as children (4). CDC reported RSV seasonality nationally, by U.S. Department of Health and Human Services (HHS) regions* and for the state of Florida, using a new statistical method that analyzes polymerase chain reaction (PCR) laboratory detections reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) (https://www.cdc.gov/surveillance/nrevss/index.html). Nationally, across three RSV seasons, lasting from the week ending July 5, 2014 through July 1, 2017, the median RSV onset occurred at week 41 (mid-October), and lasted 31 weeks until week 18 (early May). The median national peak occurred at week 5 (early February). Using these new methods, RSV season circulation patterns differed from those reported from previous seasons (5). Health care providers and public health officials use RSV circulation data to guide diagnostic testing and to time the administration of RSV immunoprophylaxis for populations at high risk for severe respiratory illness (6). With several vaccines and other immunoprophlyaxis products in development, estimates of RSV circulation are also important to the design of clinical trials and future vaccine effectiveness studies.

[Measures to be taken in adults with bronchiolitis].

PubMed

De Crémoux, Hubert

2003-02-22

The majority of bronchial and interstitial diseases of the adult are accompanied by bronchiolar inflammation, but over time the use of the term "bronchiolitis" has been limited to a few specific affections. Bronchiolitis with predominantly alveolar involvement Some "bronchiolites" emphasize the problem of an interstitial pneumopathy, since the disease predominantly involves the alveolar spaces. Only a few bronchiolites are severely damaging: bronchiolitis obliterans with organizing pneumonia and interstitial pneumopathy with respiratory bronchiolitis. These predominantly alveolar affections reveal the clinical (crepitant rales), radiographic (multiple or even diffuse opacities), and functional aspects (restrictive ventilation problems). Brochiolitis with obstructive airway problems In this case the disease predominantly involves the bronchioles and spares the alveolar tissue. The term "bronchiolitis" is in this case perfectly justified. The clinical picture is evocative with obstructed airway and a clear pulmonary parenchyma on the thoracic x-ray. These affections belong to the obstructive broncho-pneumopathy group. The prototype is brochiolitis obliterans, the anatomic correlation of which is generally constrictive bronchiolitis obliterans. Occasionally primitive, it frequently complicates the progression of many morbid states (transplants, collagenosis, inhaled or ingested toxic substances.). Diffuse panbronchiolitis Other "bronchiolites" deviate from this framework and are accompanied by marked lesions of other respiratory tracts (membrane bronchioles, cartilage bronchi, mucosa, ear nose and throat). The prototype is panbronchiolitis, described in the Far East. It is exceptional in Europe, where similar but nosologically different clinical aspects are observed during various diseases: cystic fibrosis, Young's syndrome, hypogammaglobulinemia, bone marrow transplant, context of HIV or haemorrhagic recto-colitis.

Role of bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia

USDA-ARS?s Scientific Manuscript database

Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study...

Gold nanorod vaccine for respiratory syncytial virus

NASA Astrophysics Data System (ADS)

Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E., Jr.

2013-07-01

Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response.

Oxidative Lung Injury in Virus-Induced Wheezing

DTIC Science & Technology

2012-05-01

Syncytial Virus Infection. Am J Physiol-Lung Cell & Mol Physiol, in press. 1 Annual Progress Report for the period ending 04/30/2012...epithelial cells infected with Respiratory Syncytial Virus: role in viral-induced Interferon Regulatory Factor activation. J Biol Chem. 276:19715-19722...severe RSV bronchiolitis. 2011. Amer J Resp Critic Care Med. 10. Kahn, J . S. 2003. Human metapneumovirus: a newly emerging respiratory pathogen

Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward.

PubMed

Jensen, Tomas Ostergaard; Stelzer-Braid, Sacha; Willenborg, Christiana; Cheung, Carol; Andresen, David; Rawlinson, William; Clezy, Kate

2016-10-01

We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema.

PubMed

Lunghi, Benedetta; De Cunto, Giovanna; Cavarra, Eleonora; Fineschi, Silvia; Bartalesi, Barbara; Lungarella, Giuseppe; Lucattelli, Monica

2015-01-01

The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a). The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis. We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure. No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS. Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells. Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli. Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis. The blockage of apoptosis interferes with the macrophage "clearance" from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells. The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes. Macrophages from smoking p66Shc-/- mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas. We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory

INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS (RSV)-INDUCED INFLAMMATION BY 3-NITROTYROSINE IN HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

Inhibition of Respiratory Syncytial Virus (RSV)-Induced Inflammation by 3-Nitrotyrosine in Human Bronchial Epithelial Cells. J. M. Soukup, MPH 1, ZW. Li, MD 2 and YC. T. Huang, MD 1. 1 NHEERL, US Environmental Protection Agency, RTP, NC and 2 CEMALB, University of North Carolina,...

Social, economic, and health impact of the respiratory syncytial virus: a systematic search.

PubMed

Díez-Domingo, Javier; Pérez-Yarza, Eduardo G; Melero, José A; Sánchez-Luna, Manuel; Aguilar, María Dolores; Blasco, Antonio Javier; Alfaro, Noelia; Lázaro, Pablo

2014-10-30

Bronchiolitis caused by the respiratory syncytial virus (RSV) and its related complications are common in infants born prematurely, with severe congenital heart disease, or bronchopulmonary dysplasia, as well as in immunosuppressed infants. There is a rich literature on the different aspects of RSV infection with a focus, for the most part, on specific risk populations. However, there is a need for a systematic global analysis of the impact of RSV infection in terms of use of resources and health impact on both children and adults. With this aim, we performed a systematic search of scientific evidence on the social, economic, and health impact of RSV infection. A systematic search of the following databases was performed: MEDLINE, EMBASE, Spanish Medical Index, MEDES-MEDicina in Spanish, Cochrane Plus Library, and Google without time limits. We selected 421 abstracts based on the 6,598 articles identified. From these abstracts, 4 RSV experts selected the most relevant articles. They selected 65 articles. After reading the full articles, 23 of their references were also selected. Finally, one more article found through a literature information alert system was included. The information collected was summarized and organized into the following topics: 1. Impact on health (infections and respiratory complications, mid- to long-term lung function decline, recurrent wheezing, asthma, other complications such as otitis and rhino-conjunctivitis, and mortality; 2. Impact on resources (visits to primary care and specialists offices, emergency room visits, hospital admissions, ICU admissions, diagnostic tests, and treatments); 3. Impact on costs (direct and indirect costs); 4. Impact on quality of life; and 5. Strategies to reduce the impact (interventions on social and hygienic factors and prophylactic treatments). We concluded that 1. The health impact of RSV infection is relevant and goes beyond the acute episode phase; 2. The health impact of RSV infection on children is

Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico.

PubMed

Gamiño-Arroyo, Ana E; Moreno-Espinosa, Sarbelio; Llamosas-Gallardo, Beatriz; Ortiz-Hernández, Ana A; Guerrero, M Lourdes; Galindo-Fraga, Arturo; Galán-Herrera, Juan F; Prado-Galbarro, Francisco J; Beigel, John H; Ruiz-Palacios, Guillermo M; Noyola, Daniel E

2017-01-01

Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. Patients ≥1 month old, who presented with an influenza-like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

PubMed

Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

2017-09-15

Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

Respiratory syncytial virus--the unrecognised cause of health and economic burden among young children in Australia.

PubMed

Ranmuthugala, Geetha; Brown, Laurie; Lidbury, Brett A

2011-06-01

Respiratory syncytial virus (RSV) presents very similar to influenza and is the principle cause of bronchiolitis in infants and young children worldwide. Yet, there is no systematic monitoring of RSV activity in Australia. This study uses existing published data sources to estimate incidence, hospitalisation rates, and associated costs of RSV among young children in Australia. Published reports from the Laboratory Virology and Serology Reporting Scheme, a passive voluntary surveillance system, and the National Hospital Morbidity Dataset were used to estimate RSV-related age-specific hospitalisation rates in New South Wales and Australia. These estimates and national USA estimates of RSV-related hospitalisation rates were applied to Australian population data to estimate RSV incidence in Australia. Direct economic burden was estimated by applying cost estimates used to derive economic cost associated with the influenza virus. The estimated RSV-related hospitalisation rates ranged from 2.2-4.5 per 1,000 among children less than 5 years of age to 8.7-17.4 per 1,000 among infants. Incidence ranged from 110.0-226.5 per 1,000 among the under five age group to 435.0-869.0 per 1,000 among infants. The total annual direct healthcare cost was estimated to be between $24 million and $50 million. Comparison with the health burdens attributed to the influenza virus and rotavirus suggests that the disease burden caused by RSV is potentially much higher. The limitations associated with using a passive surveillance system to estimate disease burden, and the need to explore further assessments and to monitor RSV activity are discussed.

Effects of Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) in the Perinatal Lamb Model of RSV

PubMed Central

Derscheid, Rachel J.; Gallup, Jack M.; Knudson, Cory J.; Varga, Steven M.; Grosz, Drew D.; van Geelen, Albert; Hostetter, Shannon J.; Ackermann, Mark R.

2013-01-01

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960’s that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3–5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants. PMID:24324695

Identification of a DRB3*1101-restricted CD4 T cell response against bovine respiratory syncytial virus

USDA-ARS?s Scientific Manuscript database

A better understanding of the immune response elicited by bovine respiratory syncytial virus (BRSV) vaccines is needed for vaccine improvement. Although killed-BRSV vaccines are available as part of multivalent products, their efficacy is controversial. We screened for BRSV-specific T cell responses...

KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection

PubMed Central

Mgbemena, Victoria; Segovia, Jesus; Chang, Te-Hung; Bose, Santanu

2013-01-01

Human respiratory syncytial virus (RSV) is a highly pathogenic lung-tropic virus that causes severe respiratory diseases. Enzymatic activity of inducible nitric oxide (iNOS) is required for NO generation. Although NO contributes to exaggerated lung disease during RSV infection, the role of NO in apoptosis during infection is not known. In addition, host trans-activator(s) required for iNOS gene expression during RSV infection is unknown. In the current study we have uncovered the mechanism of iNOS gene induction by identifying kruppel-like factor 6 (KLF6) as a critical transcription factor required for iNOS gene expression during RSV infection. Furthermore, we have also uncovered the role of iNOS as a critical host factor regulating apoptosis during RSV infection. PMID:23831683

Respiratory syncytial virus vaccines: an update on those in the immediate pipeline.

PubMed

Esposito, Susanna; Pietro, Giada Di

2016-10-01

Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection among infants and the elderly worldwide. Despite its long history, no licensed vaccine is available. Recently, advances in the knowledge of RSV biology and pathology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines. The aim of this review is to analyze RSV characteristics, to consider the history of RSV vaccines and to discuss RSV vaccines currently in development. Among the candidates in clinical trials, nanoparticle and subunit vaccines seem to be the most promising for pregnant women and the elderly, whereas live-attenuated or vector-based vaccines appear to be optimal for the pediatric population.

Molecular epidemiology of respiratory syncytial virus in The Gambia.

PubMed Central

Cane, P. A.; Weber, M.; Sanneh, M.; Dackour, R.; Pringle, C. R.; Whittle, H.

1999-01-01

Respiratory syncytial virus (RSV) infection in The Gambia occurs seasonally in association with the rainy season. This study examined the genetic variability of RSV isolates from four consecutive epidemics from 1993-6. Each epidemic was made up of a number of variants which were replaced in subsequent epidemics. Analysis of attachment (G) protein gene sequences showed that isolates were closely related to those observed in the rest of the world. However, many isolates from 1993 and 1994 were unlike other isolates observed in the developed world during this period and were more similar to isolates from 1984 in Europe. In addition, the most commonly observed genotype in the UK in the 1990s was not detected in The Gambia during this period. PMID:10098799

MicroRNA expression profiling in tonsils of calves challenged with a laboratory strain or field isolates of Bovine Respiratory Syncytial Virus

USDA-ARS?s Scientific Manuscript database

Bovine respiratory syncytial virus (BRSV) is a leading cause of bovine respiratory disease in cattle worldwide. MicroRNAs have been suggested to play a role in viral infections via their regulation of cellular molecules involved in either viral replication or in host innate immunity to infection. Th...

Respiratory Syncytial Virus-Associated Hospitalizations in Pre-Mature Infants in Lima, Peru

PubMed Central

Ochoa, Theresa J.; Bautista, Rossana; Dávila, Carmen; Salazar, José Antonio; Bazán, Carlos; Guerra, Oscar; Llanos, Jean Pierre; López, Luis; Zea-Vera, Alonso; Ecker, Lucie

2014-01-01

We conducted a prospective cohort study in four hospitals in Lima, Peru in infants with a birth weight ≤ 1,500 g followed from birth hospital discharge up to 1 year of age to determine the incidence of respiratory syncytial virus (RSV) hospitalizations. We enrolled 222 infants from March of 2009 to March of 2010: 48 infants with a birth weight < 1,000 g and 174 infants with a birth weight of 1,000–1,500 g (birth weight = 1,197 ± 224 g; gestational age = 30.1 ± 2.6 weeks). There were 936 episodes of respiratory infections; the incidence of respiratory infections during the first 1 year of life was 5.7 episodes/child-years. The incidence of RSV respiratory infections that required emergency room management was 103.9 per 1,000 child-years, and the incidence of RSV hospitalizations was 116.2 per 1,000 child-years (244.9 in infants with a birth weight < 1,000 g and 88.9 in infants 1,000–1,500 g; P < 0.05). The incidence of RSV respiratory infections that required emergency management or hospitalization is high among pre-mature infants in Lima. PMID:25294617

Respiratory syncytial virus: its transmission in the hospital environment.

PubMed

Hall, C B

1982-01-01

Respiratory syncytial virus (RSV) over the past two decades has been recognized as the most important cause of lower respiratory tract disease in infants and young children. Recently, it has also been identified as a major nosocomial hazard on pediatric wards. The potential for RSV to spread on such wards is underlined by several singular characteristics of RSV. It arrives in yearly epidemics and is highly contagious in all age groups. Immunity is of short duration, allowing repeated infections to occur. Thus, during an epidemic 20--40 percent of infants admitted for other conditions may acquire nosocomial RSV infection, as well as 50 percent of the ward personnel. The usual infection control procedures for respiratory illnesses have had limited success in controlling the spread of RSV. This may be due in part to the modes of transmission of RSV. Inoculation occurs mainly through the eye and nose, rather than the mouth. This may be via large-particle aerosols or droplets, requiring close contact. The virus, however, does not seem capable of traversing distances by small-particle aerosols. Nevertheless, it is able to remain infectious on various environmental surfaces, suggesting fomites as a source of spread. Indeed, inoculation after touching such contaminated surfaces can occur, and may be a major second means of spread, in hospitals as well as in families.

[Respiratory infections caused by respiratory syncytial virus in the adult population: description of 16 cases].

PubMed

Reina, Jordi; López, Carla

2013-08-17

Respiratory infections of viral etiology are frequent in the adult population. Those caused by respiratory syncytial virus (RSV) are a little known entity. The aim of this study was to determine the clinical and epidemiological characteristics of adult patients with respiratory infection due to RSV. We performed a prospective study from October 2012 to March 2013 on respiratory infections caused by RSV. Viral detection was performed using a technique of reverse transcription polymerase chain reaction genomic amplification in real time. We diagnosed 16 patients, 12 (75%) requiring hospitalization. Patients were grouped into immunocompromised (7 [43.7%]) and immunocompetent cases (9 cases 56.3%]). The first group included 3 patients with HIV infection (42.8%) and 4 hematologic patients (57.2%). The second group included those who had a baseline disease, 5 cases (55.5%), and those who lacked it, 4 cases (44.4%), and did not require hospitalization. The main clinical manifestations of patients prompting them to attend the Emergency Department were cough (50%), dyspnea (43.5%), fever (25%), expectoration (25%) and flu symptoms (25%). The most frequent diagnoses at discharge were pneumonia (37.5%) and flu syndrome (31.2%). Respiratory infections caused by RSV represent a rare condition that mainly affects immunocompromised patients. The underlying pathology determines the evolution of the process, which is favorable except in cases of severe immunosuppression. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Mathematical modelling of respiratory syncytial virus (RSV): vaccination strategies and budget applications.

PubMed

Acedo, L; Díez-Domingo, J; Moraño, J-A; Villanueva, R-J

2010-06-01

We propose an age-structured mathematical model for respiratory syncytial virus in which children aged <1 year are especially considered. Real data on hospitalized children in the Spanish region of Valencia were used in order to determine some seasonal parameters of the model. Weekly predictions of the number of children aged <1 year that will be hospitalized in the following years in Valencia are presented using this model. Results are applied to estimate the regional cost of paediatric hospitalizations and to perform a cost-effectiveness analysis of possible vaccination strategies.

Apnea in Children Hospitalized With Bronchiolitis

PubMed Central

Mansbach, Jonathan M.; Stevenson, Michelle; Macias, Charles G.; Fisher, Erin Stucky; Barcega, Besh; Sullivan, Ashley F.; Espinola, Janice A.; Piedra, Pedro A.; Camargo, Carlos A.

2013-01-01

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. PMID:24101759

Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins.

PubMed Central

García-Barreno, B; Palomo, C; Peñas, C; Delgado, T; Perez-Breña, P; Melero, J A

1989-01-01

Monoclonal antibodies directed against the glycoproteins of human respiratory syncytial virus were used in competitive enzyme-linked immunosorbent assays for topological mapping of epitopes. Whereas epitopes of the F glycoprotein could be ascribed to five nonoverlapping antigenic sites, anti-G antibodies recognized unique epitopes, many of whose competition profiles overlapped extensively. Variant viruses selected with a neutralizing (47F) anti-F antibody lost the binding for only 47F and 49F antibodies, which mapped in the same antigenic area. In contrast, viruses selected with an anti-G antibody lost the capacity to bind most of the anti-G antibodies, and their G protein was not recognized by an anti-virus antiserum, indicating major changes in the antigenic structure of the G molecule. Finally, we found great antigenic variation of the G protein among viral isolates. This occurred even within viruses of the same subtype with only limited divergence of amino acid sequence between strains. All of these data indicate marked differences in the antigenic organization of the G and F glycoproteins of respiratory syncytial virus; we discuss these differences in terms of the chemical structure of the glycoproteins. Images PMID:2463385

Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

PubMed Central

Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Martinón-Sánchez, José María; Justicia-Grande, Antonio; Rivero-Calle, Irene; Pinnock, Elli; Salas, Antonio; Fink, Colin

2016-01-01

Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases. PMID:26872131

Anti-RSV Peptide-Loaded Liposomes for the Inhibition of Respiratory Syncytial Virus.

PubMed

Joshi, Sameer; Chaudhari, Atul A; Dennis, Vida; Kirby, Daniel J; Perrie, Yvonne; Singh, Shree Ram

2018-05-09

Although respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infection in infants and adults, effective treatment options remain limited. To circumvent this issue, there is a novel approach, namely, the development of multifunctional liposomes for the delivery of anti RSV-peptides. While most of the peptides that are used for loading with the particulate delivery systems are the penetrating peptides, an alternative approach is the development of liposome-peptide systems, which are loaded with an RSV fusion peptide (RF-482), which has been designed to inhibit the RSV fusion and block infection. The results of this work have revealed that the liposomes themselves can serve as potential RSV inhibitors, whilst the anti-RSV-peptide with liposomes can significantly increase the RSV inhibition when compared with the anti-RSV peptide alone.

Capture-ELISA for serum IgM antibody to respiratory syncytial virus.

PubMed Central

Cevenini, R.; Donati, M.; Bertini, S.; Moroni, A.; Sambri, V.

1986-01-01

A four-component solid-phase capture enzyme immunoassay was set up to test for serum IgM antibody to respiratory syncytial (RS) virus and was compared with immunofluorescence assay (IFA). A total of 128 young children with acute respiratory infections were studied. Thirty-six were shown to be RS virus-positive by the detection of RS virus in nasopharyngeal secretions and 92 were RS virus-negative. A serum specimen was collected after admission to the hospital (days 0-4) and a further specimen was obtained during days 10-14. Out of 36 RS virus-positive patients, 28 (77.7%) were found to be positive for IgM by both capture-ELISA and IFA. Out of 92 RS virus-negative patients 5 (5.4%) were IgM-positive. Four false-positive results were obtained by IFA due to the presence of rheumatoid factor. The capture-ELISA was shown to be a reliable technique in detecting specific IgM antibody to RS virus. PMID:3540115

Detection of bovine respiratory syncytial virus infections in young dairy and beef cattle in Poland.

PubMed

Urban-Chmiel, Renata; Wernicki, Andrzej; Puchalski, Andrzej; Dec, Marta; Stęgierska, Diana; Grooms, Daniel L; Barbu, Nicolas I

2015-03-01

Bovine respiratory syncytial virus (BRSV) is a major contributor to bovine respiratory disease complex in dairy and beef calves, especially during the first year of life. There is a lack of comprehensive information about the prevalence of infection in cattle herds in Poland as well as in European countries outside the European Union. The aim of this study was to estimate the prevalence of BRSV infections in young beef and dairy cattle in southeastern Poland, a region that has direct contact with non-EU countries. Animals & methods: Nasal swabs and sera (n = 120) were obtained from young cattle aged 6-12 months from 45 farms in eastern and southeastern Poland. BRSV antigen detection in the nasal swabs was carried out using a rapid immunomigration assay used in diagnosing human respiratory syncytial virus (hRSV) infections in humans, while antibodies to BRSV were detected in the sera by ELISA antibody detection. The study confirmed the presence of BRSV infections in young cattle under 12 months of age from both dairy and beef herds. BRSV was detected in 27 of the 45 herds (60%) sampled. Findings from this study indicate a high prevalence of BRSV infections in cattle in Poland, which may have a significant influence on health status and animal performance. The prevalence of infection is similar to that in other parts of Poland and other countries in Europe. Development of strategies to reduce BRSV infections is needed to improve health and productivity.

Factors predicting life-threatening infections with respiratory syncytial virus in adult patients.

PubMed

Park, Se Yoon; Kim, Taeeun; Jang, Young Rock; Kim, Min-Chul; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2017-05-01

Respiratory syncytial virus (RSV) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. However, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with RSV. We conducted a retrospective cohort study from October 2013 to September 2015. Adult patients with RSV who visited the emergency department were enrolled. Primary outcome was life-threatening infection (admission to intensive care unit, need for ventilator care or in-hospital death). A total of 227 patients were analysed. Thirty-four (15%) were classified as having life-threatening infections. By logistic regression, lower respiratory infection, chronic lung disease and bacterial co-infection were independent predictors of life-threatening infections. We developed a simple clinical scoring system using these variables (lower respiratory tract infection = score 4, chronic respiratory disease = score 3, bacterial co-infection = score 3 and fever ≥38 °C = score 2) to predict life-threatening infection. A score of >5 differentiated life-threatening RSV from non-life-threatening RSV with 82% sensitivity (95% CI, 66-93) and 72% specificity (95% CI, 65-78). The use of a clinical scoring system based on lower respiratory infection, chronic respiratory disease, bacterial co-infection and fever appears to be useful for outcome prediction and risk stratification in order to select patients who may need early antiviral therapy.

The CD8 T Cell Response to Respiratory Virus Infections.

PubMed

Schmidt, Megan E; Varga, Steven M

2018-01-01

Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.

Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

PubMed

Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

2018-05-01

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P < 0.001). The viral mean load was 4.81 ± 1.98 log10 copies/1000 cells for patients under the age of 4-year-old (P < 0.001). The viral mean loads were 4.51 ± 2.04 cells in patients with low respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection.

PubMed

Brooks, A M; McBride, J T; McConnochie, K M; Aviram, M; Long, C; Hall, C B

1999-09-01

To estimate the incidence of clinical deterioration leading to intensive care unit transfer in previously healthy infants with respiratory syncytial virus (RSV) infection hospitalized on a general pediatric unit and, to assess the hypothesis that history, physical examination, oximetry, and chest radiographic findings at time of presentation can accurately identify these infants. A virology database was used to identify and determine the disposition of all children respiratory seasons. Index patients were all previously healthy, full-term infants admitted initially to the general inpatient services at CHaS or Rochester General Hospital, a second University of Rochester teaching hospital, whose clinical deterioration led to transfer to the pediatric intensive care unit (PICU). These infants were matched retrospectively (for year and date of infection, sex, chronologic age, and race) with two hospitalized controls who did not require PICU transfer. Chest radiographic findings, respiratory rate (RR), O(2) saturation, and presence of wheezing at time of presentation to the emergency department (ED) were compared. During the study years, 542 previously healthy, full-term infants were admitted to the general pediatric unit at CHaS with proven RSV infection. Ten (1.8%; 95% confidence interval, 0.9%, 3.4%) were transferred subsequently to the PICU, primarily for close monitoring of progressive respiratory distress. Data for these patients and 7 patients transferred from Rochester General Hospital to the PICU at the CHaS were compared with those for control patients. The mean RR in the ED (63 vs 50), and O(2) saturation in the ED (88% vs 93%) were modestly abnormal in cases compared with controls. Wheezing on examination at time of presentation and chest radiographic findings did not differ between the two groups. A RR >80 and an O(2) saturation <85% at time of

Effect of respiratory syncytial virus on the growth of hepatocellular carcinoma cell-lines

PubMed Central

Choi, Song Hee; Park, Byoung Kwon; Lee, Keun-Wook; Chang, Jun; Lee, Younghee; Kwon, Hyung-Joo

2015-01-01

In several reports, the respiratory syncytial virus (RSV) was identified as an oncolytic virus in cancer cells (e.g., lung and prostate cancer). However, the effects of RSV in hepatocellular carcinoma (HCC) cells have not yet been investigated. Here, we observed the inhibitory effects of RSV infection in HCC cell-lines. Cell growth was significantly decreased by RSV infection in BNL-HCC, Hep3B, Huh-7 and SNU-739 cells. After RSV infection, plaque formation and syncytial formation were observed in affected Hep3B and Huh-7 cells. RSV protein-expression was also detected in Hep3B and Huh-7 cells; however, only Huh-7 cells showed apoptosis after RSV infection. Furthermore, inhibition of cell migration by RSV infection was observed in BNL-HCC, Hep3B, Huh-7 and SNU-739 cells. Therefore, further investigation is required to clarify the molecular mechanism of RSV-mediated inhibition of HCC cell growth, and to develop potential RSV oncolytic viro-therapeutics. [BMB Reports 2015; 48(10): 565-570] PMID:25739391

[Respiratory syncytial virus infections in children in general practice].

PubMed

Nielsen, Lisa Monica; Halgrener, Jørgen; Hansen, Bjarne V Lühr

2003-06-30

The aim of the study was to describe the course of respiratory syncytial virus (RSV) infections in children under two years of age seen in general practice. Children under two years of age presenting acute respiratory infection during the registration period on 59 GPs' lists participated in the study. The GPs recorded data on a registration chart and a questionnaire was sent to the parents of the children in question one month after the date of inclusion. The children were tested in general practice for the presence of RSV. The GPs' objective findings and choice of treatment as well as the parents' account of the course of disease were compared in children with and without the presence of RSV. A total of 221 children participated in the study. Fifty-seven children were found RSV positive (25.8%). Among the RSV positive children there were significantly more with wheezing audibly detected with examination by stethoscope than among the RSV negative. The remaining parameters (the GP's objective examination, treatment and course of the disease) were distributed independently of the result of the RSV analysis. The results showed that RSV infections in children under two years in general practice are frequent and that the clinical picture most often is uncomplicated.

Recombinant bovine respiratory syncytial virus with deletion of the SH gene induces increased apoptosis and pro-inflammatory cytokines in vitro, and is attenuated and induces protective immunity in calves

PubMed Central

Wyld, Sara; Valarcher, Jean-Francois; Guzman, Efrain; Thom, Michelle; Widdison, Stephanie; Buchholz, Ursula J.

2014-01-01

Bovine respiratory syncytial virus (BRSV) causes inflammation and obstruction of the small airways, leading to severe respiratory disease in young calves. The virus is closely related to human (H)RSV, a major cause of bronchiolitis and pneumonia in young children. The ability to manipulate the genome of RSV has provided opportunities for the development of stable, live attenuated RSV vaccines. The role of the SH protein in the pathogenesis of BRSV was evaluated in vitro and in vivo using a recombinant (r)BRSV in which the SH gene had been deleted. Infection of bovine epithelial cells and monocytes with rBRSVΔSH, in vitro, resulted in an increase in apoptosis, and higher levels of TNF-α and IL-1β compared with cells infected with parental, wild-type (WT) rBRSV. Although replication of rBRSVΔSH and WT rBRSV, in vitro, were similar, the replication of rBRSVΔSH was moderately reduced in the lower, but not the upper, respiratory tract of experimentally infected calves. Despite the greater ability of rBRSVΔSH to induce pro-inflammatory cytokines, in vitro, the pulmonary inflammatory response in rBRSVΔSH-infected calves was significantly reduced compared with that in calves inoculated with WT rBRSV, 6 days previously. Virus lacking SH appeared to be as immunogenic and effective in inducing resistance to virulent virus challenge, 6 months later, as the parental rBRSV. These findings suggest that rBRSVΔSH may be an ideal live attenuated virus vaccine candidate, combining safety with a high level of immunogenicity. PMID:24700100

Malnutrition: a risk factor for severe respiratory syncytial virus infection and hospitalization.

PubMed

Paynter, Stuart; Ware, Robert S; Lucero, Marilla G; Tallo, Veronica; Nohynek, Hannah; Weinstein, Philip; Williams, Gail; Sly, Peter D; Simões, Eric A F

2014-03-01

Longitudinal information examining the effect of poor infant growth on respiratory syncytial virus (RSV) severity is limited. Children hospitalized with RSV lower respiratory infection represent those at the severe end of the disease spectrum. We followed up a cohort of 12,191 infants enrolled in a previous pneumococcal vaccine trial in Bohol, Philippines. Exposure measures were weight for age z-score at the first vaccination visit (median age 1.8 months) as well as the growth (the difference in weight for age z-score) between the first and third vaccination visits. The outcome was hospitalization with RSV lower respiratory infection. Children with a weight for age z-score ≤ -2 at their first vaccination visit had the highest rate of hospitalization with RSV lower respiratory infection, but this association was only evident in children whose mothers had >10 years of education (hazard ratio: 3.38; 95% confidence interval: 1.63-6.98). Children who had lower than median growth between their first and third vaccinations had a higher rate of RSV-associated hospitalization than those with growth above the median (hazard ratio: 1.34; 95% confidence interval: 1.02-1.76). Poor infant growth increases the risk for severe RSV infection leading to hospitalization.

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children

PubMed Central

Mazur, Natalie I.; Bont, Louis; Cohen, Adam L.; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J.; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K.; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A.

2017-01-01

Background Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Methods Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009–December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Results Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)–associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39–1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6–7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0–4.5; P = .05) compared with RSV monoinfection. Conclusions RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. PMID:27927871

Constrictive (obliterative) bronchiolitis.

PubMed

Schlesinger, C; Veeraraghavan, S; Koss, M N

1998-09-01

Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.

Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

PubMed

Pickles, Raymond J

2013-01-01

Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys.

PubMed

Sawada, Akihito; Yunomae, Kiyokazu; Nakayama, Tetsuo

2018-02-01

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK-C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Effect of climatological factors on respiratory syncytial virus epidemics

PubMed Central

NOYOLA, D. E.; MANDEVILLE, P. B.

2008-01-01

SUMMARY Respiratory syncytial virus (RSV) presents as yearly epidemics in temperate climates. We analysed the association of atmospheric conditions to RSV epidemics in San Luis Potosí, S.L.P., Mexico. The weekly number of RSV detections between October 2002 and May 2006 were correlated to ambient temperature, barometric pressure, relative humidity, vapour tension, dew point, precipitation, and hours of light using time-series and regression analyses. Of the variation in RSV cases, 49·8% was explained by the study variables. Of the explained variation in RSV cases, 32·5% was explained by the study week and 17·3% was explained by meteorological variables (average daily temperature, maximum daily temperature, temperature at 08:00 hours, and relative humidity at 08:00 hours). We concluded that atmospheric conditions, particularly temperature, partly explain the year to year variability in RSV activity. Identification of additional factors that affect RSV seasonality may help develop a model to predict the onset of RSV epidemics. PMID:18177520

Incidence of Respiratory Disease During the First Two Years of Life in Children with Hemodynamically Significant Congenital Heart Disease in Italy: A Retrospective Study.

PubMed

Pongiglione, Giacomo; Possidoni, Alessandro; di Luzio Paparatti, Umberto; Costanzo, Anna Maria; Gualberti, Giuliana; Bonvicini, Marco; Rimini, Alessandro; Agnoletti, Gabriella; Calabrò, Maria Pia; Pozzi, Marco; Tumbarello, Roberto; Salice, Patrizia; Fiorini, Patrizio; Russo, Maria Giovanna; Milanesi, Ornella

2016-12-01

Children affected by hemodynamically significant congenital heart disease (HSCHD) experience severe respiratory complications that can increase the frequency of hospitalizations. The aim of the SINERGY study was to describe the incidence of respiratory diseases and to collect information on active and passive immunoprophylaxis in the first 2 years of life. In this retrospective, multicenter, and epidemiologic study, children with HSCHD were enrolled across 11 Italian sites. Children born between December 31, 2007, and December 31, 2012, were observed during their first 2 years of life. Data were collected through hospital database searches and parent interviews. Four hundred twenty children were enrolled: 51.7 % were female, 79.5 % were born full-term (≥37 weeks), and 77.6 % weighed >2500 g at birth. The most frequent heart defects were ventricular septal defect (23.1 %) and coarctation of the aorta (14.3 %). The incidence of respiratory diseases was 63.1 %. Frequent respiratory diseases not requiring hospitalization were upper respiratory tract infections (76.4 %), acute bronchitis (43.3 %), and influenza (22.1 %), while those requiring hospitalization were bronchitis and bronchiolitis (8.3 % each one). While active immunoprophylaxis was applied with wide compliance (diphtheria/pertussis/tetanus, 99.5 %; Haemophilus influenzae type b, 72.5 %; pneumococcus, 79.9 %; meningococcus, 77.4 %), only 54 % of children received respiratory syncytial virus (RSV) passive prophylaxis (palivizumab). Of the 35 hospitalizations due to bronchiolitis, 27 (77.1 %) did not receive prophylaxis against RSV, compared with 8 (22.9 %) who received prophylaxis (P < 0.0001). Children with HSCHD are at major risk of respiratory diseases. Passive immunoprophylaxis can help to prevent hospitalizations for bronchiolitis.

Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

PubMed

Barik, Sailen

2013-01-01

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family that consists of viruses with nonsegmented negative-strand RNA genome. Infection by these viruses triggers the innate antiviral response of the host, mainly type I interferon (IFN). Essentially all other viruses of this family produce IFN suppressor functions by co-transcriptional RNA editing. In contrast, RSV has evolved two unique nonstructural proteins, NS1 and NS2, to effectively serve this purpose. Together, NS1 and NS2 degrade or sequester multiple signaling proteins that affect both IFN induction and IFN effector functions. While the mechanism of action of NS1 and NS2 is a subject of active research, their effect on adaptive immunity is also being recognized. In this review, we discuss various aspects of NS1 and NS2 function with implications for vaccine design.

Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country.

PubMed

Rodríguez-Martínez, Carlos E; Rodríguez, Diego Andrés; Nino, Gustavo

2015-05-01

There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV-adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2-year period 2009-2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3-month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre-existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05-2.89; P = 0.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01-100.9; P = 0.049) were independent predictors of mixed RSV-adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV-adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country. © 2015 Wiley Periodicals, Inc.

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.

PubMed

Mazur, Natalie I; Bont, Louis; Cohen, Adam L; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A

2017-02-15

Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39-1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection. RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Steam inhalation or humidified oxygen for acute bronchiolitis in children up to three years of age.

PubMed

Umoren, Rachel; Odey, Friday; Meremikwu, Martin M

2011-01-19

Acute bronchiolitis is a common respiratory infection and a major cause of morbidity in young children. It is treated with bronchodilators (for example, salbutamol), corticosteroids or humidified air (steam inhalation or cool mist). Steam inhalation is preferred in low-income countries as it is inexpensive and easily available. It is thought to act as a secretolytic agent to lighten secretions in the respiratory tract and relieve respiratory distress. To evaluate the effect of steam inhalation or humidified oxygen to relieve respiratory distress and to evaluate adverse events in children up to three years old with acute bronchiolitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to February Week 4, 2010), EMBASE.com (1974 to March 2010), CINAHL (1981 to March 2010), AMED (1985 to March 2010), Web of Science (2000 to March 2010) and LILACS (1982 to March 2010). Randomised controlled trials involving children up to three years old with bronchiolitis comparing steam inhalation (or cool mist) or humidified oxygen against bronchodilators, corticosteroids or placebo; alone or in combination. Two review authors independently assessed trial quality and extracted data. Only one study (156 children aged between seven weeks and 24 months with signs and symptoms of bronchiolitis) met the eligibility criteria for inclusion. Participants were randomised into three groups: nebulised salbutamol, nebulised saline and mist in a tent. The results showed a significant decrease in respiratory distress symptom (RDS) score in the nebulised salbutamol group but no significant decrease in the RDS score in the mist in a tent or nebulised saline groups. The study did not report on adverse effects of the interventions. Steam inhalation (or cool mist therapy) is commonly used to treat acute bronchiolitis in resource-constrained settings

Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting.

PubMed

Moyes, Jocelyn; Walaza, Sibongile; Pretorius, Marthi; Groome, Michelle; von Gottberg, Anne; Wolter, Nicole; Haffejee, Sumayya; Variava, Ebrahim; Cohen, Adam L; Tempia, Stefano; Kahn, Kathleen; Dawood, Halima; Venter, Marietjie; Cohen, Cheryl; Madhi, Shabir A

2017-10-01

There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013. Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay. The incidence of RSV-associated SARI was calculated for the one site with population denominators. Of 7796 participants investigated, 329 (4%) tested positive for RSV. On multivariable analysis, HIV-infected individuals with RSV-associated SARI had greater odds of being in the age groups 18-44 and 45-64 years (odd ratios (OR) 26.3; 95% confidence interval (CI) 6.2-112.1 and OR 11.4; 95% CI 2.6-50.0) compared with those ≥65 years and being female (OR 2.7; 95% CI 1.4-5.4). The relative risk of hospitalization with RSV-associated SARI was 12-18 times higher in HIV infected individual compared to that of HIV-uninfected. The incidence of RSV-associated SARI was higher in HIV-infected individuals and those aged 65 years and older. Further studies are warranted to describe the disease association of RSV detected in adults with SARI. Copyright © 2017 The British Infection Association. All rights reserved.

Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge

PubMed Central

Phan, Shannon I.; Zengel, James R.; Wei, Huiling; Li, Zhuo

2017-01-01

ABSTRACT Human respiratory syncytial virus (RSV) is the leading cause of pediatric bronchiolitis and hospitalizations. RSV can also cause severe complications in elderly and immunocompromised individuals. There is no licensed vaccine. We previously generated a parainfluenza virus 5 (PIV5)-vectored vaccine candidate expressing the RSV fusion protein (F) that was immunogenic and protective in mice. In this work, our goal was to improve the original vaccine candidate by modifying the PIV5 vector or by modifying the RSV F antigen. We previously demonstrated that insertion of a foreign gene at the PIV5 small hydrophobic (SH)–hemagglutinin-neuraminidase (HN) junction or deletion of PIV5 SH increased vaccine efficacy. Additionally, other groups have demonstrated that antibodies against the prefusion conformation of RSV F have more potent neutralizing activity than antibodies against the postfusion conformation. Therefore, to improve on our previously developed vaccine candidate, we inserted RSV F at the PIV5 SH-HN gene junction or used RSV F to replace PIV5 SH. We also engineered PIV5 to express a prefusion-stabilized F mutant. The candidates were tested in BALB/c mice via the intranasal route and induced both humoral and cell-mediated immunity. They also protected against RSV infection in the mouse lung. When they were administered intranasally or subcutaneously in cotton rats, the candidates were highly immunogenic and reduced RSV loads in both the upper and lower respiratory tracts. PIV5-RSV F was equally protective when administered intranasally or subcutaneously. In all cases, the prefusion F mutant did not induce higher neutralizing antibody titers than wild-type F. These results show that antibodies against both pre- and postfusion F are important for neutralizing RSV and should be considered when designing a vectored RSV vaccine. The findings also that indicate PIV5-RSV F may be administered subcutaneously, which is the preferred route for vaccinating infants

Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge.

PubMed

Phan, Shannon I; Zengel, James R; Wei, Huiling; Li, Zhuo; Wang, Dai; He, Biao

2017-10-01

Human respiratory syncytial virus (RSV) is the leading cause of pediatric bronchiolitis and hospitalizations. RSV can also cause severe complications in elderly and immunocompromised individuals. There is no licensed vaccine. We previously generated a parainfluenza virus 5 (PIV5)-vectored vaccine candidate expressing the RSV fusion protein (F) that was immunogenic and protective in mice. In this work, our goal was to improve the original vaccine candidate by modifying the PIV5 vector or by modifying the RSV F antigen. We previously demonstrated that insertion of a foreign gene at the PIV5 small hydrophobic (SH)-hemagglutinin-neuraminidase (HN) junction or deletion of PIV5 SH increased vaccine efficacy. Additionally, other groups have demonstrated that antibodies against the prefusion conformation of RSV F have more potent neutralizing activity than antibodies against the postfusion conformation. Therefore, to improve on our previously developed vaccine candidate, we inserted RSV F at the PIV5 SH-HN gene junction or used RSV F to replace PIV5 SH. We also engineered PIV5 to express a prefusion-stabilized F mutant. The candidates were tested in BALB/c mice via the intranasal route and induced both humoral and cell-mediated immunity. They also protected against RSV infection in the mouse lung. When they were administered intranasally or subcutaneously in cotton rats, the candidates were highly immunogenic and reduced RSV loads in both the upper and lower respiratory tracts. PIV5-RSV F was equally protective when administered intranasally or subcutaneously. In all cases, the prefusion F mutant did not induce higher neutralizing antibody titers than wild-type F. These results show that antibodies against both pre- and postfusion F are important for neutralizing RSV and should be considered when designing a vectored RSV vaccine. The findings also that indicate PIV5-RSV F may be administered subcutaneously, which is the preferred route for vaccinating infants, who may

Different meteorological parameters influence metapneumovirus and respiratory syncytial virus activity.

PubMed

Darniot, Magali; Pitoiset, Cécile; Millière, Laurine; Aho-Glélé, Ludwig Serge; Florentin, Emmanuel; Bour, Jean-Baptiste; Manoha, Catherine

2018-05-05

Both human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) cause epidemics during the cold season in temperate climates. The purpose of this study was to find out whether climatic factors are associated with RSV and hMPV epidemics. Our study was based on data from 4300 patients admitted to the Dijon University Hospital for acute respiratory infection (ARI) over three winter seasons chosen for their dissimilar meteorological and virological patterns. Cases of hMPV and RSV were correlated with meteorological parameters recorded in the Dijon area. The relationship between virus data and local meteorological conditions was analyzed by univariate and multivariate negative binomial regression analysis. RSV detection was inversely associated with temperature and positively with relative humidity and air pressure, whereas hMPV was inversely associated with temperature and positively with wind speed. The association among meteorological variables and weekly ARIs cases due to RSV and hMPV demonstrated the relevance of climate factors as contributors to both hMPV and RSV activities. Meteorological drivers of RSV and hMPV epidemics are different. Low temperatures influence both hMPV and RSV activity. Relative humidity is an important predictor of RSV activity, but it does not influence hMPV activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute bronchiolitis in a paediatric emergency department of Northern Greece. Comparisons between two decades

PubMed Central

Emporiadou, Maria; Aivazis, Victor; Mauromixalis, John; Hatzistilianou, Maria

2012-01-01

Introduction Acute bronchiolitis is the most common lower respiratory tract infection in infants and toddlers concerning small bronchi or bronchioli. This retrospective study aimed to evaluate the incidence of acute bronchiolitis and the use of β2-agonists between two different decades. Material and methods During 1990-1991 and 2001-2002, the files of the 2nd Paediatric Emergency Department of Aristotle University of Thessaloniki, AHEPA Hospital were reviewed and cases of acute bronchiolitis were recorded and analysed. Results During 1990-1991, 14 538 children were identified with respiratory infections and bronchiolitis was diagnosed in 519/14 538 children (3.56%). Only 34 out of 519 patients received nebulised salbutamol (6.6%) and 221/519 were hospitalized (42.6%). During 2001-2002, 9001 children were found to have respiratory tract infections and acute bronchiolitis was diagnosed in 641/9001 of them (7.12%). In total, 411/641 children (64.1%) received salbutamol and ipratropium, and 89/641 patients (13.88%) were hospitalized. There was a predominance of male sex in both decades (p = 0.509). There was a statistically significant difference (p < 0.001) concerning the use of nebulised salbutamol with nebulised ipratropium between the two decades. Finally, during 2001-2002, the use of bronchodilators with or without corticosteroids was more frequent and it appears to be correlated with the reduced number of admissions to hospital (p < 0.05) compared with 1990-1991. Conclusions There was an increase in the incidence of acute bronchiolitis during the last decade. The admission rate decreased probably due to the use of nebulized salbutamol and ipratropium, but further multicentre comparative trials are required to define the role of bronchodilators in the treatment of acute bronchiolitis. PMID:22852008

Environmental exposure of primary care personnel to ribavirin aerosol when supervising treatment of infants with respiratory syncytial virus infections.

PubMed Central

Rodriguez, W J; Bui, R H; Connor, J D; Kim, H W; Brandt, C D; Parrott, R H; Burch, B; Mace, J

1987-01-01

The potential exposure to ribavirin aerosol in the environment was assessed in nurses caring for infants and children with severe lower respiratory tract infections due to respiratory syncytial virus. Ribavirin aerosol was administered via a ventilator, oxygen tent, or oxygen hood. Participants worked directly with infants receiving ribavirin for 20.0 to 35.0 h over a 3-day period. No toxic or adverse effects of ribavirin aerosol were observed in any of the 19 nurses studied, and ribavirin was not detected in erythrocytes, plasma, or urine collected after the potential exposure period. PMID:3662474

Increased respiratory disease mortality at a microwave popcorn production facility with worker risk of bronchiolitis obliterans.

PubMed

Halldin, Cara N; Suarthana, Eva; Fedan, Kathleen B; Lo, Yi-Chun; Turabelidze, George; Kreiss, Kathleen

2013-01-01

Bronchiolitis obliterans, an irreversible lung disease, was first associated with inhalation of butter flavorings (diacetyl) in workers at a microwave popcorn company. Excess rates of lung-function abnormalities were related to cumulative diacetyl exposure. Because information on potential excess mortality would support development of permissible exposure limits for diacetyl, we investigated respiratory-associated mortality during 2000-2011 among current and former workers at this company who had exposure to flavorings and participated in cross-sectional surveys conducted between 2000-2003. We ascertained workers' vital status through a Social Security Administration search. Causes of death were abstracted from death certificates. Because bronchiolitis obliterans is not coded in the International Classification of Disease 10(th) revision (ICD-10), we identified respiratory mortality decedents with ICD-10 codes J40-J44 which encompass bronchitis (J40), simple and mucopurulent chronic bronchitis (J41), unspecified chronic bronchitis (J42), emphysema (J43), and other chronic obstructive pulmonary disease (COPD) (J44). We calculated expected number of deaths and standardized mortality ratios (SMRs) with 95% confidence intervals (CI) to determine if workers exposed to diacetyl experienced greater respiratory mortality than expected. We identified 15 deaths among 511 workers. Based on U.S. population estimates, 17.39 deaths were expected among these workers (SMR = 0.86; CI:0.48-1.42). Causes of death were available for 14 decedents. Four deaths among production and flavor mixing workers were documented to have a multiple cause of 'other COPD' (J44), while 0.98 'other COPD'-associated deaths were expected (SMR = 4.10; CI:1.12-10.49). Three of the 4 'other COPD'-associated deaths occurred among former workers and workers employed before the company implemented interventions reducing diacetyl exposure in 2001. Workers at the microwave popcorn company experienced

Comparison of Cepheid Xpert Flu/RSV XC and BioFire FilmArray for Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus.

PubMed

Wahrenbrock, Mark G; Matushek, Scott; Boonlayangoor, Sue; Tesic, Vera; Beavis, Kathleen G; Charnot-Katsikas, Angella

2016-07-01

The Xpert Flu/RSV XC was compared to the FilmArray respiratory panel for detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV), using 128 nasopharyngeal swabs. Positive agreements were 100% for Flu A and RSV and 92.3% for Flu B. The Xpert may be useful in clinical situations when extensive testing is not required and may serve an important role in laboratories already performing broader respiratory panel testing. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Incidence of Medically Attended Respiratory Syncytial Virus and Influenza Illnesses in Children 6-59 Months Old During Four Seasons.

PubMed

Simpson, Melissa D; Kieke, Burney A; Sundaram, Maria E; McClure, David L; Meece, Jennifer K; Sifakis, Frangiscos; Gasser, Robert A; Belongia, Edward A

2016-04-01

Background.  Respiratory syncytial virus (RSV) and influenza are significant causes of seasonal respiratory illness in children. The incidence of influenza and RSV hospitalization is well documented, but the incidence of medically attended, laboratory-confirmed illness has not been assessed in a well defined community cohort. Methods.  Children aged 6-59 months with medically attended acute respiratory illness were prospectively enrolled during the 2006-2007 through 2009-2010 influenza seasons in a Wisconsin community cohort. Nasal swabs were tested for RSV and influenza by multiplex reverse-transcription polymerase chain reaction. The population incidence of medically attended RSV and influenza was estimated separately and standardized to weeks 40 through 18 of each season. Results.  The cohort included 2800-3073 children each season. There were 2384 children enrolled with acute respiratory illness; 627 (26%) were positive for RSV and 314 (13%) for influenza. The mean age was 28 months (standard deviation [SD] = 15) for RSV-positive and 38 months (SD = 16) for influenza-positive children. Seasonal incidence (cases per 10 000) was 1718 (95% confidence interval [CI], 1602-1843) for RSV and 768 (95% CI, 696-848) for influenza. Respiratory syncytial virus incidence was highest among children 6-11 (2927) and 12-23 months old (2377). Influenza incidence was highest (850) in children 24-59 months old. The incidence of RSV was higher than influenza across all seasons and age groups. Conclusions.  The incidence of medically attended RSV was highest in children 6-23 months old, and it was consistently higher than influenza. The burden of RSV remains high throughout the first 2 years of life.

Respiratory syncytial virus subunit vaccine based on a recombinant fusion protein expressed transiently in mammalian cells.

PubMed

Nallet, Sophie; Amacker, Mario; Westerfeld, Nicole; Baldi, Lucia; König, Iwo; Hacker, David L; Zaborosch, Christiane; Zurbriggen, Rinaldo; Wurm, Florian M

2009-10-30

Although respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in infants and adults at risk, no RSV vaccine is currently available. In this report, efforts toward the generation of an RSV subunit vaccine using recombinant RSV fusion protein (rRSV-F) are described. The recombinant protein was produced by transient gene expression (TGE) in suspension-adapted human embryonic kidney cells (HEK-293E) in 4 L orbitally shaken bioreactors. It was then purified and formulated in immunostimulating reconstituted influenza virosomes (IRIVs). The candidate vaccine induced anti-RSV-F neutralizing antibodies in mice, and challenge studies in cotton rats are ongoing. If successful in preclinical and clinical trials, this will be the first recombinant subunit vaccine produced by large-scale TGE in mammalian cells.

Performance of the Alere i RSV assay for point-of-care detection of respiratory syncytial virus in children.

PubMed

Schnee, Sarah Valerie; Pfeil, Johannes; Ihling, Clara Marlene; Tabatabai, Julia; Schnitzler, Paul

2017-12-13

Respiratory syncytial virus (RSV) is the most important cause of severe acute respiratory tract infection in young children. Alere i RSV is a novel molecular rapid test which identifies respiratory syncytial virus in less than 13 min. We evaluated the clinical performance of the Alere i RSV assay in a pediatric point-of-care setting during winter season 2016 / 2017. Test results from 518 nasopharyngeal swab samples were compared to a real-time reverse transcription PCR reference standard. The overall sensitivity and specificity of the Alere i RSV test assay was 93% (CI 95 89% - 96%) and 96% (CI 95 93% - 98%), respectively. Alere i RSV performed well in children of all age groups. An optimal sensitivity of 98% (CI 95 94% - 100%) and specificity of 96% (CI 95 90% - 99%) was obtained in children < 6 months. In children ≥ 2 years, sensitivity and specificity remained at 87% (CI 95 73% - 96%) and 98% (CI 95 92% - 100%), respectively. False negative Alere i RSV test results mostly occurred in samples with low viral load (mean CT value 31.1; CI 95 29.6 - 32.6). The Alere i RSV assay is easy to use and can be operated after minimal initial training. Test results are available within 13 min, with most RSV positive samples being identified after approximately 5 min. The Alere i RSV assay has the potential to facilitate the detection of RSV in pediatric point-of-care settings.

Respiratory syncytial virus seasonality and its implications on prevention strategies.

PubMed

Janet, Sophie; Broad, Jonathan; Snape, Matthew D

2018-01-02

With maternal and infant vaccines against respiratory syncytial virus (RSV) in development, it is timely to consider how the deployment of these vaccines might vary according to local RSV disease seasonality. In temperate regions RSV infection is predictably limited to a period of 3 to 5 months, while in tropical regions disease seasonality is often both more variable and more prolonged. Accordingly, in tropical regions a year-round immunisation schedule for both maternal and infant immunisation might be appropriate. In contrast, in temperate regions the benefit of year-round maternal immunisation would be heavily dependent on the duration of protection this provided, potentially necessitating a strategy directed at children due to be born in the months immediately prior to the RSV season. This review will consider the impact of seasonality on maternal and infant immunisation strategies against RSV, and the potential of an alternative approach of passive immunisation for all infants immediately prior to the RSV season.

Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway

PubMed Central

2014-01-01

Background Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. Results BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. Conclusion The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV. PMID:24423030

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

PubMed Central

Tripp, Ralph A.; Moore, Deborah; Winter, Jorn; Anderson, Larry J.

2000-01-01

A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice and the effect of anti-SP F(ab)2 antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment of RSV-infected mice with anti-SP F(ab)2 antibodies suggested that SP may alter the natural killer cell response to primary and secondary infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest that SP may be an important contributor to the inflammatory response to RSV infection and that anti-SP F(ab)2 antibodies might be used to ameliorate RSV-associated disease. PMID:10644330

Nosocomial Transmission of Respiratory Syncytial Virus in an Outpatient Cancer Center

PubMed Central

Chu, Helen Y.; Englund, Janet A.; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P.; Boeckh, Michael; Pergam, Steven A.; Casper, Crey

2014-01-01

Background Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. Methods We performed a retrospective cohort study of two nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance (SCCA). Subjects included patients seen at the SCCA with RSV detected in two outbreaks in 2007-2008 and 2012, and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested polymerase chain reaction targeting the RSV attachment glycoprotein coding region. Results Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 (67%) of 15 patients with RSV sequenced from 2007-2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; nine (90%) of 10 patients had the same viral strain, and 1 (10%) had another viral strain. Conclusions We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. PMID:24607551

Respiratory Syncytial Virus in Otherwise Healthy Prematurely Born Infants: A Forgotten Majority.

PubMed

Paes, Bosco

2018-05-01

Healthy, premature infants ≤35 weeks' gestational age (wGA) are universally recognized to be at an increased risk of perinatal morbidity and mortality. Serious respiratory syncytial virus (RSV) lower respiratory tract infection imposes an additional burden of illness on these infants following hospitalization. Incurred morbidities relative to term infants include longer lengths of hospital stay, admission to intensive care, and need for oxygen and mechanical ventilation, all of which are associated with increased hospital costs. The highest morbidities are experienced by premature infants who are youngest (<3 months' chronological age) and are of lower gestational age. Short- and long-term follow-up indicates that healthy preterm infants both of lower gestational age and who are late preterm have obstructive lung function at baseline, which is further compromised by RSV-related infection during infancy. There is increasing evidence that childhood exposure to an episode of RSV infection may set the stage for an abnormal respiratory function trajectory, which, in adulthood, leads to chronic obstructive pulmonary disease. Healthy premature infants <32 wGA merit RSV prophylaxis based on existing data, whereas moderate- and high-risk preterm infants 32 to 35 wGA should be selectively and cost-effectively targeted for prophylaxis using validated risk scoring tools and country-specific thresholds for funding. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of Alere i RSV for Rapid Detection of Respiratory Syncytial Virus in Children Hospitalized with Acute Respiratory Tract Infection.

PubMed

Peters, Rebecca Marie; Schnee, Sarah Valerie; Tabatabai, Julia; Schnitzler, Paul; Pfeil, Johannes

2017-04-01

Alere i RSV is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. In this study, we evaluated the Alere i RSV assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. Alere i RSV assay results were compared to those for Altona RealStar RSV real-time reverse transcription-PCR (RT-PCR). We found that the overall sensitivity and specificity of the Alere i RSV test was 100% (95% confidence intervals [CI], 93% to 100%) and 97% (95% CI, 89% to 100%), respectively. Positive samples were identified within 5 to 7 min from sample collection. Overall, the Alere i RSV test performed well compared to the RT-PCR assay and has the potential to facilitate the detection of RSV in point-of-care settings. Copyright © 2017 Peters et al.

Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon.

PubMed

Finianos, Mayda; Issa, Randi; Curran, Martin D; Afif, Claude; Rajab, Maryam; Irani, Jihad; Hakimeh, Noha; Naous, Amal; Hajj, Marie-Joelle; Hajj, Pierre; El Jisr, Tamima; El Chaar, Mira

2016-11-01

Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Monitoring respiratory syncytial virus through the Spanish influenza surveillance system, 2006-2014].

PubMed

Jiménez-Jorge, Silvia; Delgado-Sanz, Concepción; de Mateo, Salvador; Pozo, Francisco; Casas, Inmaculada; Larrauri, Amparo

2016-02-01

The aim of the study is to analyze the information on respiratory syncytial virus (RSV) obtained through the Spanish Influenza Surveillance System (SISS) and to study its usefulness as supplementary information for the characterization of influenza epidemics. The temporal patterns of both RSV and influenza viruses were analyzed by patterns comparing the weekly viral detection rates from 2006 to 2014. In general, the RSV circulation was characterized by showing a peak between 52-1 weeks, and circulated from 2 to 8 weeks before/prior to influenza viruses. RSV information obtained from the SISS is useful for the characterization of influenza epidemics in Spain. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

PubMed

Bajimaya, Shringkhala; Frankl, Tünde; Hayashi, Tsuyoshi; Takimoto, Toru

2017-10-01

Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

PubMed Central

Fonseca, Wendy; Lukacs, Nicholas W.; Ptaschinski, Catherine

2018-01-01

Respiratory syncytial virus (RSV) is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection. PMID:29515570

Respiratory Syncytial Virus Infection: Mechanisms of Redox Control and Novel Therapeutic Opportunities

PubMed Central

Garofalo, Roberto P.; Kolli, Deepthi

2013-01-01

Abstract Respiratory syncytial virus (RSV) is one of the most important causes of upper and lower respiratory tract infections in infants and young children, for which no effective treatment is currently available. Although the mechanisms of RSV-induced airway disease remain incompletely defined, the lung inflammatory response is thought to play a central pathogenetic role. In the past few years, we and others have provided increasing evidence of a role of reactive oxygen species (ROS) as important regulators of RSV-induced cellular signaling leading to the expression of key proinflammatory mediators, such as cytokines and chemokines. In addition, RSV-induced oxidative stress, which results from an imbalance between ROS production and airway antioxidant defenses, due to a widespread inhibition of antioxidant enzyme expression, is likely to play a fundamental role in the pathogenesis of RSV-associated lung inflammatory disease, as demonstrated by a significant increase in markers of oxidative injury, which correlate with the severity of clinical illness, in children with RSV infection. Modulation of ROS production and oxidative stress therefore represents a potential novel pharmacological approach to ameliorate RSV-induced lung inflammation and its long-term consequences. Antioxid. Redox Signal. 18, 186–217. PMID:22799599

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

PubMed

Scheltema, Nienke M; Gentile, Angela; Lucion, Florencia; Nokes, D James; Munywoki, Patrick K; Madhi, Shabir A; Groome, Michelle J; Cohen, Cheryl; Moyes, Jocelyn; Thorburn, Kentigern; Thamthitiwat, Somsak; Oshitani, Hitoshi; Lupisan, Socorro P; Gordon, Aubree; Sánchez, José F; O'Brien, Katherine L; Gessner, Bradford D; Sutanto, Agustinus; Mejias, Asuncion; Ramilo, Octavio; Khuri-Bulos, Najwa; Halasa, Natasha; de-Paris, Fernanda; Pires, Márcia Rosane; Spaeder, Michael C; Paes, Bosco A; Simões, Eric A F; Leung, Ting F; da Costa Oliveira, Maria Tereza; de Freitas Lázaro Emediato, Carla Cecília; Bassat, Quique; Butt, Warwick; Chi, Hsin; Aamir, Uzma Bashir; Ali, Asad; Lucero, Marilla G; Fasce, Rodrigo A; Lopez, Olga; Rath, Barbara A; Polack, Fernando P; Papenburg, Jesse; Roglić, Srđan; Ito, Hisato; Goka, Edward A; Grobbee, Diederick E; Nair, Harish; Bont, Louis J

2017-10-01

Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle

Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors

PubMed Central

Brüggmann, Dörthe; Köster, Corinna; Klingelhöfer, Doris; Bauer, Jan; Ohlendorf, Daniela; Bundschuh, Matthias; Groneberg, David A

2017-01-01

Objective Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research. Design Retrospective, descriptive study. Setting The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools. Results We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil. Conclusions The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these

Strategies for preventing respiratory syncytial virus.

PubMed

Forbes, Michael

2008-12-01

Prevention of respiratory syncytial virus (RSV) infection-crucial for decreasing the burden associated with this disease-is discussed. Predictable outbreaks of RSV occur annually throughout the U.S. During these outbreaks, RSV infection spreads readily among children through close contact with infected individuals or contact with contaminated surfaces or objects. RSV is the leading cause of infant hospitalization and is associated with life-changing and life-threatening complications. Prevention is important for reducing the associated morbidity and mortality. The American Academy of Pediatrics (AAP) has outlined ways to prevent RSV transmission. According to the AAP, frequent hand washing is the most important strategy for reducing the burden of RSV disease. Other methods for controlling nosocomial spread of RSV include the use of gloves, frequent glove changes, and isolating or cohorting patients. General prevention measures that can be undertaken by family members include smoking cessation, breastfeeding, and avoiding situations, whenever possible, where exposure to RSV cannot be controlled. Passive immunoprophylaxis with palivizumab, the only agent approved by the FDA, reduces hospitalization in high-risk children. Palivizumab is currently the only agent approved by the FDA for the prevention of RSV infections in high-risk children. Not every child is equally at risk for serious RSV disease, and immunoprophylaxis is indicated only for certain high-risk children. The AAP has issued specific guidelines for RSV immunoprophylaxis with palivizumab. Other therapies are emerging for the prevention of RSV, including a new, enhanced-potency, humanized RSV monoclonal antibody and several different types of vaccines. RSV causes an annual, predictable epidemic. Treatment remains exclusively supportive. Prevention remains the cornerstone of disease management. The AAP has issued guidelines to protect those at high risk.

Nosocomial transmission of respiratory syncytial virus in an outpatient cancer center.

PubMed

Chu, Helen Y; Englund, Janet A; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P; Boeckh, Michael; Pergam, Steven A; Casper, Corey

2014-06-01

Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. We performed a retrospective cohort study of 2 nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance. Subjects included patients seen at the Seattle Cancer Care Alliance with RSV detected in 2 outbreaks in 2007-2008 and 2012 and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested PCR targeting the RSV attachment glycoprotein coding region. Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 of 15 patients (67%) with RSV sequenced from 2007 to 2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; 9 of 10 patients (90%) had the same viral strain, and 1 (10%) had another viral strain. We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.

Nasal Continuous Positive Airway Pressure in Bronchiolitis: A Randomized Controlled Trial.

PubMed

Lal, Sandeep Narayan; Kaur, Jaspreet; Anthwal, Pooja; Goyal, Kanika; Bahl, Pinky; Puliyel, Jacob M

2018-01-15

To evaluate the efficacy of nasal continuous positive airway pressure (nCPAP) in decreasing respiratory distress in bronchiolitis. Randomized controlled trial. Tertiary-care hospital in New Delhi, India. Participants: 72 infants (age <1y) hospitalized with a clinical diagnosis of bronchiolitis were randomized to receive standard care, or nCPAP in addition to standard care, in the first hour after admission. 23 parents refused to give consent for participation. 2 infants did not tolerate nCPAP. 72 infants (age <1y) hospitalized with a clinical diagnosis of bronchiolitis were randomized to receive standard care, or nCPAP in addition to standard care, in the first hour after admission. 23 parents refused to give consent for participation. 2 infants did not tolerate nCPAP. The outcome was assessed after 60 minutes. If nCPAP was not tolerated or the distress increased, the infant was switched to standard care. Analysis was done on intention-to-treat basis. Change in respiratory rate, Silverman-Anderson score and a Modified Pediatric Society of New Zealand Severity Score. 14 out of 32 in nCPAP group and 5 out of 35 in standard care group had change in respiratory rate ≥10 (P=0.008). The mean (SD) change in respiratory rate [8.0 (5.8) vs 5.1 (4.0), P=0.02] in Silverman-Anderson score [0.78 (0.87) vs 0.39 (0.73), P=0.029] and in Modified Pediatric Society of New Zealand Severity Score [2.5 (3.01) vs. 1.08 (1.3), P=0.012] were significantly different in the nCPAP and standard care groups, respectively. nCPAP helped reduce respiratory distress significantly compared to standard care.

Increased Respiratory Disease Mortality at a Microwave Popcorn Production Facility with Worker Risk of Bronchiolitis Obliterans

PubMed Central

Halldin, Cara N.; Suarthana, Eva; Fedan, Kathleen B.; Lo, Yi-Chun; Turabelidze, George; Kreiss, Kathleen

2013-01-01

Background Bronchiolitis obliterans, an irreversible lung disease, was first associated with inhalation of butter flavorings (diacetyl) in workers at a microwave popcorn company. Excess rates of lung-function abnormalities were related to cumulative diacetyl exposure. Because information on potential excess mortality would support development of permissible exposure limits for diacetyl, we investigated respiratory-associated mortality during 2000–2011 among current and former workers at this company who had exposure to flavorings and participated in cross-sectional surveys conducted between 2000–2003. Methods We ascertained workers' vital status through a Social Security Administration search. Causes of death were abstracted from death certificates. Because bronchiolitis obliterans is not coded in the International Classification of Disease 10th revision (ICD-10), we identified respiratory mortality decedents with ICD-10 codes J40–J44 which encompass bronchitis (J40), simple and mucopurulent chronic bronchitis (J41), unspecified chronic bronchitis (J42), emphysema (J43), and other chronic obstructive pulmonary disease (COPD) (J44). We calculated expected number of deaths and standardized mortality ratios (SMRs) with 95% confidence intervals (CI) to determine if workers exposed to diacetyl experienced greater respiratory mortality than expected. Results We identified 15 deaths among 511 workers. Based on U.S. population estimates, 17.39 deaths were expected among these workers (SMR = 0.86; CI:0.48-1.42). Causes of death were available for 14 decedents. Four deaths among production and flavor mixing workers were documented to have a multiple cause of ‘other COPD’ (J44), while 0.98 ‘other COPD’-associated deaths were expected (SMR = 4.10; CI:1.12–10.49). Three of the 4 ‘other COPD’-associated deaths occurred among former workers and workers employed before the company implemented interventions reducing diacetyl exposure in 2001. Conclusion

Pulmonary delivery of respiratory syncytial virus DNA vaccines using macroaggregated albumin particles.

PubMed

Harcourt, Jennifer L; Anderson, Larry J; Sullender, Wayne; Tripp, Ralph A

2004-06-02

At present there is no safe and effective vaccine for respiratory syncytial virus (RSV). DNA vaccines encoding RSV surface glycoproteins are one option being examined. Current methods to deliver DNA vaccines generally require repeated high dose intramuscular or intradermal administration for effectiveness. In this study, we examine the efficacy of pulmonary DNA vaccination using low dose DNA vaccines encoding the RSV F glycoprotein conjugated to macroaggregated albumin (MAA-F). Single vaccination of BALB/c mice with 1 microg MAA-F was ineffective, however mice boosted with an additional 1 microg MAA-F, or vaccinated a single time with 10 microg MAA-F, developed substantially improved immunity associated with reduced viral titers, increased anti-F antibody responses, and enhanced Th1 and Th2 intracellular cytokine responses. This study shows that MAA may be a useful carrier for RSV DNA vaccines.

Respiratory syncytial virus epidemiology in a birth cohort from Kilifi district, Kenya: infection during the first year of life.

PubMed

Nokes, D James; Okiro, Emelda A; Ngama, Mwanajuma; White, Lisa J; Ochola, Rachel; Scott, Paul D; Cane, Patricia A; Medley, Graham F

2004-11-15

We report estimates of incidence of respiratory syncytial virus (RSV) infection during the first year of life for a birth cohort from rural, coastal Kenya. A total of 338 recruits born between 21 January 2002 and 30 May 2002 were monitored for symptoms of respiratory infection by home visits and hospital referrals. Nasal washings were screened by use of immunofluorescence. From 311 child-years of observation (cyo), 133 RSV infections were found, of which 48 were lower respiratory tract infections (LRTIs) and 31 were severe LRTIs, resulting in 4 hospital admissions. There were 121 primary RSV infections (248 cyo), of which 45 were LRTIs and 30 were severe LRTIs, resulting in 4 hospital admissions; there was no association with age. RSV contributed significantly to total LRTI disease in this vaccine-target group.

[Potential neurocognitive consequences of infection by human respiratory syncytial virus].

PubMed

Flores, Juan Carlos; Bohmwald, Karen; Espinoza, Janyra; Jara, Crlstlna; Peña, Marcela; Hoyos-Bachiloglu, Rodrigo; Iturriaga, Carolina; Kalergis, Alexis M; Borzutzky, Arturo

2016-10-01

Human respiratory syncytial virus (RSV) infection remains as a major cause of morbidity and mortality among pediatric population. Immune response is poor and unable to establish a long term effective protection against this virus. Of particular interest has been the description of extrapulmonary manifestations of RSV infection in liver, kidney, endocrine system, heart and brain, associated to infection of peripheral blood. In the central nervous system (CNS), recent studies in animals have suggested long term neurocognitive impairment due to a direct damage from the virus. This was prevented in rats by a recombinant BCG vaccine expressing a nucleoprotein N of RSV that produces an effective immune response against the virus, not allowing its dissemination to the CNS. These findings in animal models highlight the importance of conducting more specific studies in children affected with severe infection by RSV. Therefore, our group is currently conducting an assessment of the possible long-term cognitive impairment in children under 2 years. The results of this study could be a strong argument to continue looking for an effective method for protecting against RSV infection.

Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

PubMed

Kim, Young-In; Murphy, Ryan; Majumdar, Sirshendu; Harrison, Lisa G; Aitken, Jody; DeVincenzo, John P

2015-10-01

Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model

PubMed Central

de Waal, Leon; Smits, Saskia L.; Veldhuis Kroeze, Edwin J. B.; van Amerongen, Geert; Pohl, Marie O.; Osterhaus, Albert D. M. E.; Stittelaar, Koert J.

2018-01-01

Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV. PMID:29301313

Risk factors for recurrent wheezing following acute bronchiolitis: a 12-month follow-up.

PubMed

Cifuentes, Lorena; Caussade, Solange; Villagrán, Claudia; Darrigrande, Paula; Bedregal, Paula; Valdivia, Gonzalo; Sánchez, Ignacio

2003-10-01

The objective of this study was to identify wheezing recurrences and related risk factors in two groups of infants with bronchiolitis: respiratory syncytial virus (RSV)+ and RSV- as determined by RSV enzyme immunoassay. A 1-year prospective cohort study was conducted with infants younger than 2 years old. Follow-up was made monthly, by a clinical visit and/or by telephone, checking the number of wheezing episodes per month and possible related risk factors. There were 96 subjects enrolled, of whom 77 reached complete follow-up: 36 were RSV+ (46.8%), and 41 were RSV- (53.2%). In the RSV+ group, there were 17 males (47%), vs. RSV- with 30 males (73%) (P < 0.05); 22 RSV+ (61%) were admitted to hospital, vs.14 RSV- (34%) (P < 0.05). Mean age was not significantly different in both groups. The mean number of recurrences was 3.36 episodes/infant/year in the RSV+ and 2.34 in the RSV- group (P = 0.06). Crude relative risk (RR) for a new recurrence of an obstructive episode was 1.33 (95% CI, 0.99-1.79). After adjustment for several potential confounders, the RR was 1.41 (95% CI, 1.03-1.93). Hospitalization stay was longer in the RSV+ than the RSV- group (P < 0.05). In the RSV+ group, patients who had been hospitalized showed more recurrences (4.18) than those with outpatient treatment (2.07) (P < 0.05); this difference did not exist in the RSV- group. The related risk factors for recurrent wheeze in the RSV- group were male gender, number of siblings, and daycare attendance (P < 0.05). In the RSV+ group, the risk of recurrent wheeze was only increased by admission to hospital during the acute bronchiolitis episode (P < 0.05). We speculate that there may be a higher rate of increased airway reactivity and/or preexisting diminished lung function in RSV+ infants requiring hospitalization for their initial illness. In conclusion, RSV-proven bronchiolitis, particularly in those infants who are hospitalized, is associated with a higher recurrence of wheezing episodes in the

Therapeutic approach to bronchiolitis: why pediatricians continue to overprescribe drugs?

PubMed Central

2010-01-01

Background Bronchiolitis guidelines suggest that neither bronchodilators nor corticosteroids, antiviral and antibacterial agents should be routinely used. Although recommendations, many clinicians persistently prescribe drugs for bronchiolitis. Aim of the study To unravel main reasons of pediatricians in prescribing drugs to infants with bronchiolitis, and to possibly correlate therapeutic choices to the severity of clinical presentation. Also possible influence of socially deprived condition on therapeutic choices is analyzed. Methods Patients admitted to Pediatric Division of 2 main Hospitals of Naples because of bronchiolitis in winter season 2008-2009 were prospectively analyzed. An RDAI (Respiratory Distress Assessment Instrument) score was assessed at different times from admission. Enrolment criteria were: age 1-12 months; 1st lower respiratory infection with cough and rhinitis with/without fever, wheezing, crackles, tachypnea, use of accessory muscles, and/or nasal flaring, low oxygen saturation, cyanosis. Social deprivation status was assessed by evaluating school graduation level of the origin area of the patients. A specific questionnaire was submitted to clinicians to unravel reasons of their therapeutic behavior. Results Eighty-four children were enrolled in the study. Mean age was 3.5 months. Forty-four per cent of patients presented with increased respiratory rate, 70.2% with chest retractions, and 7.1% with low SaO2. Mean starting RDAI score was 8. Lung consolidation was found in 3.5% on chest roentgenogram. Data analysis also unraveled that 64.2% matched clinical admission criteria. Social deprivation status analysis revealed that 72.6% of patients were from areas "at social risk". Evaluation of length of stay vs. social deprivation status evidenced no difference between "at social risk" and "not at social risk" patients. Following therapeutic interventions were prescribed: nasal suction (64.2%), oxygen administration (7.1%), antibiotics (50

Intensive Care Unit Admission and Death Rates of Infants Admitted With Respiratory Syncytial Virus Lower Respiratory Tract Infection in Mexico.

PubMed

Vizcarra-Ugalde, Sergio; Rico-Hernández, Montserrat; Monjarás-Ávila, César; Bernal-Silva, Sofía; Garrocho-Rangel, Maria E; Ochoa-Pérez, Uciel R; Noyola, Daniel E

2016-11-01

Respiratory syncytial virus (RSV) is the most common etiology for acute respiratory infection hospital admissions in young children. Case fatality rates for hospitalized patients range between 0% and 3.4%. Recent reports indicate that deaths associated with RSV are uncommon in developed countries. However, the role of this virus as a current cause of mortality in other countries requires further examination. Children with RSV infection admitted between May 2003 and December 2014 to a level 2 specialty hospital in Mexico were included in this analysis. Underlying risk factors, admission to the intensive care unit (ICU) and condition on discharge were assessed to determine the ICU admission and death rates associated to RSV infection. We analyzed data of 1153 patients with RSV infection in whom information regarding underlying illnesses and discharge status was available. Sixty patients (5.2 %) were admitted to the ICU and 12 (1.04 %) died. Relevant underlying conditions were present in 320 (27.7%) patients. Infants with underlying respiratory disorders (excluding asthma) and a history of prematurity had high ICU admission rates (17.1% and 13.8%, respectively). Mortality rates were highest for infants with respiratory disease (excluding asthma) (7.3%), cardiovascular diseases (5.9%) and neurologic disorders (5.3%). The ICU admission and death rates were higher in infants <6 months of age than in other age groups. The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively. Mortality rates were high in infants with respiratory, cardiovascular and neurologic disorders.

Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials

PubMed Central

Beran, Jiři; Lickliter, Jason D; Schwarz, Tino F; Johnson, Casey; Chu, Laurence; Domachowske, Joseph B; Van Damme, Pierre; Withanage, Kanchanamala; Fissette, Laurence A; David, Marie-Pierre; Maleux, Koen; Schmidt, Alexander C; Picciolato, Marta; Dieussaert, Ilse

2018-01-01

Abstract Background Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns. Methods Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18–45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV–prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap. Results Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1–3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90. Conclusions All formulations of RSV-PreF boosted preexisting immune responses in 18–45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine. PMID:29401325

Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.

PubMed

Wong, Terianne M; Petrovsky, Nikolai; Bissel, Stephanie J; Wiley, Clayton A; Ross, Ted M

2016-08-02

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax TM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either Advax TM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax TM was similar to Imject Alum. Overall, RSV vaccine formulated with Advax TM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared

Down syndrome as risk factor for respiratory syncytial virus hospitalization: A prospective multicenter epidemiological study.

PubMed

Sánchez-Luna, Manuel; Medrano, Constancio; Lirio, Julián

2017-03-01

Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality. To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection. In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season. The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively. Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil

PubMed Central

2012-01-01

Background Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV) as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP) in Belém city, Pará (Northern Brazil). Methods With the objective of determining the prevalence of RSV infection and evaluating the patients’ clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR) for RSV Group identification. Results RSV infection was detected in 243 (23.1%) children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, p<0.001) whereas gender distribution was similar. The RSV-positive group showed lower means of C-reactive protein (CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p<0.05). Radiological findings showed that 54.2% of RSV-positive group and 50.3% of RSV-negative group had interstitial infiltrate. Bacterial infection was identified predominantly in the RSV-positive group (10% vs 4.5%, p<0.05). Rhinorrhea and nasal obstruction were predominantly observed in the RSV-positive group. A co-circulation of RSV Groups A and B was identified, with a predominance of Group B (209/227). Multivariate analysis revealed that age under 1 year (p<0.015), CRP levels under 48 mg/dL (p<0.001) and bacterial co-infection (p<0.032) were independently associated with the presence of RSV and, in the analyze of symptoms, nasal obstruction

Strain-specific reverse transcriptase PCR assay: means to distinguish candidate vaccine from wild-type strains of respiratory syncytial virus.

PubMed Central

Zheng, H; Peret, T C; Randolph, V B; Crowley, J C; Anderson, L J

1996-01-01

Candidate live-virus vaccines for respiratory syncytial virus are being developed and are beginning to be evaluated in clinical trials. To distinguish candidate vaccine strains from wild-type strains isolated during these trials, we developed PCR assays specific to two sets of candidate vaccine strains. The two sets were a group A strain (3A), its three attenuated, temperature-sensitive variant strains, a group B strain (2B), and its four attenuated, temperature-sensitive variant strains. The PCR assays were evaluated by testing 18 group A wild-type strains, the 3A strains, 9 group B wild-type strains, and the 2B strains. PCR specific to group A wild-type strains amplified only group A wild-type strains, and 3A-specific PCR amplified only 3A strains. PCR specific to group B wild-type strains amplified all group A and group B strains but gave a 688-bp product for group B wild-type strains, a 279-bp product for 2B strains, a 547-bp product for all group A strains, and an additional 688-bp product for some group A strains, including 3A strains. These types of PCR assays can, in conjunction with other methods, be used to efficiently distinguish candidate vaccine strains from other respiratory syncytial virus strains. PMID:8789010

Respiratory Syncytial Virus (RSV) Infects CD4+ T Cells: Frequency of Circulating CD4+ RSV+ T Cells as a Marker of Disease Severity in Young Children.

PubMed

Raiden, Silvina; Sananez, Inés; Remes-Lenicov, Federico; Pandolfi, Julieta; Romero, Cecilia; De Lillo, Leonardo; Ceballos, Ana; Geffner, Jorge; Arruvito, Lourdes

2017-04-01

Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4+ T cells to RSV infection. CD4+ and CD8+ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4+ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria. CD4+ and CD8+ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4+ T cells. Respiratory syncytial virus antigens were detected in circulating CD4+ and CD8+ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4+ RSV+ T cells positively correlated with disease severity. Respiratory syncytial virus infects CD4+ and CD8+ T cells and compromises T-cell function. The frequency of circulating CD4+ RSV+ T cells might represent a novel marker of severe infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

PubMed Central

Fearns, Rachel; Graham, Barney S.

2016-01-01

Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naïve recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies. PMID:24362682

Improved clinical and economic outcomes in severe bronchiolitis with pre-emptive nCPAP ventilatory strategy.

PubMed

Essouri, Sandrine; Laurent, Marie; Chevret, Laurent; Durand, Philippe; Ecochard, Emmanuelle; Gajdos, Vincent; Devictor, Denis; Tissières, Pierre

2014-01-01

Severe bronchiolitis is the leading cause of admission to the pediatric intensive care unit (PICU). Nasal continuous positive airway pressure (nCPAP) has become the primary respiratory support, replacing invasive mechanical ventilation (MV). Our objective was to evaluate the economic and clinical consequences following implementation of this respiratory strategy in our unit. This was a retrospective cohort analysis of 525 infants with bronchiolitis requiring respiratory support and successively treated during two distinct periods with invasive MV between 1996 and 2000, P1 (n = 193) and nCPAP between 2006 and 2010, P2 (n = 332). Costs were estimated using the hospital cost billing reports. Patients' baseline characteristics were similar between the two periods. P2 is associated with a significant decrease in the length of ventilation (LOV) (4.1 ± 3.5 versus 6.9 ± 4.6 days, p < 0.001), PICU length of stay (LOS) (6.2 ± 4.6 versus 9.7 ± 5.5 days, p < 0.001) and hospital LOS. nCPAP was independently associated with a shorter duration of ventilatory support than MV (hazard ratio 1.8, 95% CI 1.5-2.2, p < 0.001). nCPAP was also associated with a significant decrease in ventilation-associated complications, and less invasive management. The mean cost of acute viral bronchiolitis-related PICU hospitalizations was significantly decreased, from 17,451 to 11,205 € (p < 0.001). Implementation of nCPAP led to a reduction of the total annual cost of acute viral bronchiolitis hospitalizations of 715,000 €. nCPAP in severe bronchiolitis is associated with a significant improvement in patient management as shown by the reduction in invasive care, LOV, PICU LOS, hospital LOS, and economic burden.

Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

2017-11-02

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Increase of CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells.

PubMed

Kunzmann, Steffen; Krempl, Christine; Seidenspinner, Silvia; Glaser, Kirsten; Speer, Christian P; Fehrholz, Markus

2018-04-16

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase of CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

RSV prophylaxis guideline changes and outcomes in children with congenital heart disease.

PubMed

Walpert, Adam S; Thomas, Ian D; Lowe, Merlin C; Seckeler, Michael D

2018-05-01

The aim of this study was to compare inpatient outcomes and costs for children with respiratory syncytial virus and congenital heart disease before and after the change in management guidelines for respiratory syncytial virus prophylaxis. Hospital discharge data from the Vizient (formerly University HealthSystem Consortium) were queried from October 2012 to June 2014 (Era 1) and July 2014 to April 2016 (Era 2) for patients aged <24 months with an any International Classification of Disease (ICD)-9 or ICD-10 code for congenital heart disease (745-747.49, Q20.0-Q26.4) and a primary or secondary admitting diagnosis of respiratory syncytial virus infection (079.6, J20.5), acute bronchiolitis due to respiratory syncytial virus (466.11, J21.0) or respiratory syncytial virus pneumonia (480.1, J12.1). This study is a review of a national administrative discharge database. Respiratory syncytial virus admissions were identified in 1269 patients aged <24 months with congenital heart disease, with 644 patients in Era 1 and 625 in Era 2. Patients 0-12 months old represented 83% of admissions. Prior to 2014, children aged 0-24 months with congenital heart disease were eligible to receive respiratory syncytial virus prophylaxis. Updated guidelines, published in 2014, restricted the recommendation to administer palivizumab respiratory syncytial virus prophylaxis to children with congenital heart disease only if they are ≤12 months old. The outcome measures are hospital length of stay, ICU admission rate, mortality, and direct costs. There was no change in length of stay, ICU admission rate, in-hospital mortality, or direct costs for children 13-24 months old with congenital heart disease after the change in guidelines. There were no deaths in 13-24 month olds, regardless of era. Our findings provide additional support for the new guideline recommendations to provide respiratory syncytial virus prophylaxis only for children ≤12 months old with congenital heart disease. �

Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication

PubMed Central

Bakre, Abhijeet; Mitchell, Patricia; Coleman, Jonathan K.; Jones, Les P.; Saavedra, Geraldine; Teng, Michael; Tompkins, S. Mark

2012-01-01

Respiratory syncytial virus (RSV) causes substantial morbidity and life-threatening lower respiratory tract disease in infants, young children and the elderly. Understanding the host response to RSV infection is critical for developing disease-intervention approaches. The role of microRNAs (miRNAs) in post-transcriptional regulation of host genes responding to RSV infection is not well understood. In this study, it was shown that RSV infection of a human alveolar epithelial cell line (A549) induced five miRNAs (let-7f, miR-24, miR-337-3p, miR-26b and miR-520a-5p) and repressed two miRNAs (miR-198 and miR-595), and showed that RSV G protein triggered let-7f expression. Luciferase–untranslated region reporters and miRNA mimics and inhibitors validated the predicted targets, which included cell-cycle genes (CCND1, DYRK2 and ELF4), a chemokine gene (CCL7) and the suppressor of cytokine signalling 3 gene (SOCS3). Modulating let-7 family miRNA levels with miRNA mimics and inhibitors affected RSV replication, indicating that RSV modulates host miRNA expression to affect the outcome of the antiviral host response, and this was mediated in part through RSV G protein expression. PMID:22894925

A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)

PubMed Central

Phan, Shannon I.; Chen, Zhenhai; Xu, Pei; Li, Zhuo; Gao, Xiudan; Foster, Stephanie L.; Teng, Michael N.; Tripp, Ralph A.; Sakamoto, Kaori; He, Biao

2014-01-01

Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses - one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection. PMID:24717150

Outcome of the Respiratory Syncytial Virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study.

PubMed

Alan, Serdar; Erdeve, Omer; Cakir, Ufuk; Akduman, Hasan; Zenciroglu, Aysegul; Akcakus, Mustafa; Tunc, Turan; Gokmen, Zeynel; Ates, Can; Atasay, Begum; Arsan, Saadet

2016-01-01

To determine the incidence and outcomes of respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs). A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip®-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions. The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU. RSV-associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU.

A prospective randomised trial comparing nasogastric with intravenous hydration in children with bronchiolitis (protocol) The comparative rehydration in bronchiolitis study (CRIB)

PubMed Central

2010-01-01

Background Bronchiolitis is the most common reason for admission of infants to hospital in developed countries. Fluid replacement therapy is required in about 30% of children admitted with bronchiolitis. There are currently two techniques of fluid replacement therapy that are used with the same frequency-intravenous (IV) or nasogastric (NG). The evidence to determine the optimum route of hydration therapy for infants with bronchiolitis is inadequate. This randomised trial will be the first to provide good quality evidence of whether nasogastric rehydration (NGR) offers benefits over intravenous rehydration (IVR) using the clinically relevant continuous outcome measure of duration of hospital admission. Methods/Design A prospective randomised multi-centre trial in Australia and New Zealand where children between 2 and 12 months of age with bronchiolitis, needing non oral fluid replacement, are randomised to receive either intravenous (IV) or nasogastric (NG) rehydration. 750 patients admitted to participating hospitals will be recruited, and will be followed daily during the admission and by telephone 1 week after discharge. Patients with chronic respiratory, cardiac, or neurological disease; choanal atresia; needing IV fluid resuscitation; needing an IV for other reasons, and those requiring CPAP or ventilation are excluded. The primary endpoint is duration of hospital admission. Secondary outcomes are complications, need for ICU admission, parental satisfaction, and an economic evaluation. Results will be analysed using t-test for continuous data, and chi squared for categorical data. Non parametric data will be log transformed. Discussion This trial will define the role of NGR and IVR in bronchiolitis Trail registration The trial is registered with the Australian and New Zealand Clinical Trials Registry - ACTRN12605000033640 PMID:20515467

Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine.

PubMed

Lee, Young J; Lee, Jeong Y; Jang, Yo H; Seo, Sang-Uk; Chang, Jun; Seong, Baik L

2018-01-01

The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3 -/- TLR7 -/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors.

PubMed

Brüggmann, Dörthe; Köster, Corinna; Klingelhöfer, Doris; Bauer, Jan; Ohlendorf, Daniela; Bundschuh, Matthias; Groneberg, David A

2017-07-26

Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research. Retrospective, descriptive study. The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools. We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil. The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries. © Article author(s) (or their employer

Incidence and Clinical Features of Respiratory Syncytial Virus Infections in a Population-Based Surveillance Site in the Nile Delta Region

DTIC Science & Technology

2013-01-01

S U P P L E M E N T A R T I C L E Incidence and Clinical Features of Respiratory Syncytial Virus Infections in a Population-Based Surveillance Site...19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c . THIS PAGE unclassified Standard Form 298 (Rev. 8-98...Patients of any age were eligible if they presented with ≥1 sign of acute infection, (docu- mented fever ≥38° C or history of subjective fever with

Respiratory Syncytial Virus Preterm (32-36 Completed Weeks of Gestation) Risk Estimation Measure for RSV Hospitalization in Ireland: A Prospective Study.

PubMed

Sheridan-Pereira, Margaret; Murphy, Joan; Sloan, Julie; Crispino, Gloria; Leahy, Anne; Corcoran, J David; Dempsey, Eugene; Elnazir, Basil; Gavin, Patrick; Sharif, Farhana; Gul, Rizwan; Satas, Salius; Murphy, John; Gormally, Siobhan; Shanaa, Issam; Waldron, David; Mc Mahon, Paul; Carson, John; Blanken, Maarten; Bont, Louis; Paes, Bosco

2016-01-01

In several countries, respiratory syncytial virus prophylaxis is offered to late preterm infants who are at escalated risk of respiratory syncytial virus hospitalization (RSVH). However, targeted prophylaxis should be informed by country-specific data. This study, which uniquely includes 36 weeks of gestational age (GA) infants, aims to establish the risk factors for RSVH in 32-36 weeks of GA infants in Ireland. A prospective observational study at 13 hospitals of laboratory-confirmed RSVH in nonprophylaxed 32-36 weeks of GA infants was conducted from July 2011 to February 2014. Baseline and first-year clinical data were analyzed by using SPSS software Version 22 (IBM Corp, Armonk, NY). Significant (P < 0.05) variables were entered into multiple logistic regression to determine the independent risk factors for RSVH. Sixty-three percent of eligible infants (1825 of 2877) were recruited. The RSVH rate was 3.6% (65 of 1807 analyzed infant records). There was no RSV-attributable mortality. Twelve infants required intensive care. Of the 15 variables correlating to RSVH, 5 independent risk factors were identified: older siblings [odds ratio (OR): 3.8; 95% confidence interval (CI): 1.97-7.41], being Caucasian (OR: 2.3; 95% CI: 1.04-5.29), neonatal respiratory morbidity (OR: 2.2; 95% CI: 1.28-3.94); birth July 15 to December 15 (OR: 2.1; 95% CI: 1.09-3.92) and family history of asthma (OR: 1.9; 95% CI: 1.01-3.39). Birth from 36 weeks to 36 + 6 days mitigated RSVH risk (relative risk: 0.58; 95% CI: 0.34-0.99); however, risk factors were similar to the 32-35 weeks of GA cohort. Neonatal respiratory morbidity or being Caucasian were the population-specific independent risk factors for RSVH in 32-36 weeks of GA in Ireland, whereas the other identified independent risk factors mirrored those established in previous studies.

Immunomodulatory constituents of human breast milk and immunity from bronchiolitis.

PubMed

Li, Chunyu; Liu, Yanbo; Jiang, Yanfang; Xu, Naijun; Lei, Jie

2017-01-14

The mother's immune status can be achieved by genetic and breastfeeding impact descendants of the immune system. The study aimed to determine whether a mother's immune status and breastfeeding practices were related to development of bronchiolitis in her infant. The frequency of T, B and natural kill (NK) cells in patients' blood and their mothers' breast milk was determined using flow cytometry. The concentrations of serum and breast milk IgG and IgD in individual patients and healthy control were determined by enzyme-linked immunosorbent assay (ELISA). The relationships between immunocytes, immunoglobulin and respiratory score (RS) were analyzed by Spearman's rank correlation test. The mothers of bronchiolitis patients had lower IgG concentrations in their breast milk when compared to the mothers of healthy children. There was no significant difference in the frequency of T cells, B cells, and NK cells in samples of breast milk. However, significant decreases of CD3+, CD8+ T cells, as well as significant increases of CD4+ T cells and CD19+ B cells were found in the serum of bronchiolitis infants. There were positive correlation relationships between RS and CD3+, CD4+ T cells, IgG and IgD concentrations. Our data suggested that the mothers of bronchiolitis patients had lower IgG concentration in their breast milk. The breast milk IgG might be absorbed by the breastfeeding infants, which could play important role in resistance of bronchiolitis.

Respiratory infections in children up to two years of age on prophylaxis with palivizumab

PubMed Central

Monteiro, Ana Isabel M. P.; Bellei, Nancy Cristina J.; Sousa, Alessandra Ramos; dos Santos, Amélia Miyashiro N.; Weckx, Lily Yin

2014-01-01

OBJECTIVE: To identify the viruses involved in acute respiratory tract infections and to analyze the rates of hospitalization and death in children on palivizumab prophylaxis. METHODS: Prospective cohort of 198 infants up to one year old who were born before 29 weeks of gestational age and infants under two years old with hemodynamically unstable cardiopathy or chronic pulmonary disease who received prophylactic palivizumab against severe respiratory syncytial virus infections in 2008. During the study period, in each episode of acute respiratory tract infection, nasopharyngeal aspirate was collected to identify respiratory syncytial virus, adenovirus, parainfluenza 1, 2 and 3, influenza A and B by direct immunofluorescence, rhinovirus and metapneumovirus by polymerase chain reaction preceded by reverse transcription. Data regarding hospitalization and deaths were monitored. RESULTS: Among the 198 studied infants, 117 (59.1%) presented acute respiratory tract infections, with a total of 175 episodes. Of the 76 nasopharyngeal aspirates collected during respiratory tract infections, 37 were positive, as follow: rhinovirus (75.7%), respiratory syncytial virus (18.9%), parainfluenza (8.1%), adenovirus 2 (2.7%), metapneumovirus (2.7%) and three samples presented multiple agents. Of the 198 children, 48 (24.4%) were hospitalized: 30 (15.2%) for non-infectious etiology and 18 (9.1%) for respiratory causes. Among these 18 children, one case of respiratory syncytial virus was identified. Two deaths were reported, but respiratory syncytial virus was not identified. CONCLUSIONS: During the prophylaxis period, low frequency of respiratory syncytial virus infections and low rates of hospitalization were observed, suggesting the benefit of palivizumab prophylaxis. PMID:25119744

Evaluation of Seegene Allplex Respiratory Panel 1 kit for the detection of influenza virus and human respiratory syncytial virus.

PubMed

Gimferrer, Laura; Andrés, Cristina; Rando, Ariadna; Piñana, Maria; Codina, Maria Gema; Martin, Maria Del Carmen; Fuentes, Francisco; Rubio, Susana; Alcubilla, Pilar; Pumarola, Tomàs; Antón, Andrés

2018-05-25

Influenza (FLUV) and human respiratory syncytial (HRSV) viruses are etiological agents of respiratory infections that cause a significant morbidity and mortality worldwide. A rapid and accurate diagnosis of these respiratory viruses is essential for an appropriate patient management. Molecular tests are the best detection option due to their high sensitivity and specificity. Seegene's Allplex™ Respiratory Panel 1 (Allplex RP1) is a real-time one-step RT-PCR assay for the simultaneous detection of FLUAV, FLUBV, HRSV-A and HRSV-B. In addition, it allows the determination of FLUAV subtype (H1, H3 and H1pdm09). This study aims to evaluate Allplex RP1 as a rapid molecular test for the detection of FLUAV, FLUBV, HRSV-A and HRSV-B viruses. The Allplex RP1 assay will be compared with other two commercial molecular assays, Prodesse ProFlu+ and ProFAST+ (Hologic, Madison, WI, USA), and GeneXpert Flu/RSV XC (Cepheid, USA). Allplex RP1, ProFlu+ and GeneXpert tests showed 95%, 91% and 96% of accuracy; and 94%, 88% and 95% of sensitivity, respectively. Moreover, Allplex RP1 showed a FLUAV subtype sensitivity of 91% and 88% for FLUAV-H1pdm09 and FLUAV-H3 respectively, and ProFAST+ assay showed sensitivities of 100% for both targets. The three assays showed a 100% of specificity and PPV, while the NPV were 84%, 73% and 86% for Allplex RP1, Prodesse and GeneXpert, respectively. In this study, Seegene's Allplex RP1 assay showed to be highly sensitive, specific, and suitable for detection of FLUV and HRSV, including FLUAV subtyping. In addition, it is also a hands-on-time saving assay due to the automated nucleic acid extraction and PCR setup. Copyright © 2018. Published by Elsevier B.V.

Economic evaluation of nasogastric versus intravenous hydration in infants with bronchiolitis.

PubMed

Oakley, Ed; Carter, Rob; Murphy, Bridie; Borland, Meredith; Neutze, Jocelyn; Acworth, Jason; Krieser, David; Dalziel, Stuart; Davidson, Andrew; Donath, Susan; Jachno, Kim; South, Mike; Babl, Franz E

2017-06-01

Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospitalisation. We aimed to assess whether intravenous hydration (IVH) was more cost-effective than nasogastric hydration (NGH) as a planned secondary economic analysis of a randomised trial involving 759 infants (aged 2-12 months) admitted to hospital with a clinical diagnosis of bronchiolitis and requiring non-oral hydration. No Australian cost data exist to aid clinicians in decision-making around interventions in bronchiolitis. Cost data collections included hospital and intervention-specific costs. The economic analysis was reduced to a cost-minimisation study, focusing on intervention-specific costs of IVH versus NGH, as length of stay was equal between groups. All analyses are reported as intention to treat. Intervention costs were greater for IVH than NGH ($113 vs $74; cost difference of $39 per child). The intervention-specific cost advantage to NGH was robust to inter-site variation in unit prices and treatment activity. Intervention-specific costs account for <10% of total costs of bronchiolitis admissions, with NGH having a small cost saving across all sites. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Occurrence of human respiratory syncytial virus in summer in Japan.

PubMed

Shobugawa, Y; Takeuchi, T; Hibino, A; Hassan, M R; Yagami, R; Kondo, H; Odagiri, T; Saito, R

2017-01-01

In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.

A multi-tiered time-series modelling approach to forecasting respiratory syncytial virus incidence at the local level.

PubMed

Spaeder, M C; Fackler, J C

2012-04-01

Respiratory syncytial virus (RSV) is the most common cause of documented viral respiratory infections, and the leading cause of hospitalization, in young children. We performed a retrospective time-series analysis of all patients aged <18 years with laboratory-confirmed RSV within a network of multiple affiliated academic medical institutions. Forecasting models of weekly RSV incidence for the local community, inpatient paediatric hospital and paediatric intensive-care unit (PICU) were created. Ninety-five percent confidence intervals calculated around our models' 2-week forecasts were accurate to ±9·3, ±7·5 and ±1·5 cases/week for the local community, inpatient hospital and PICU, respectively. Our results suggest that time-series models may be useful tools in forecasting the burden of RSV infection at the local and institutional levels, helping communities and institutions to optimize distribution of resources based on the changing burden and severity of illness in their respective communities.

Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

PubMed

Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

2017-11-01

Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

2'-5'-Oligoadenylate Synthetase-Like Protein Inhibits Respiratory Syncytial Virus Replication and Is Targeted by the Viral Nonstructural Protein 1.

PubMed

Dhar, Jayeeta; Cuevas, Rolando A; Goswami, Ramansu; Zhu, Jianzhong; Sarkar, Saumendra N; Barik, Sailen

2015-10-01

2'-5'-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein. Here we describe differential inhibitory activities of human OASL and the two mouse OASL homologs against respiratory syncytial virus (RSV) replication. Interestingly, nonstructural protein 1 (NS1) of RSV promoted proteasome-dependent degradation of specific OASL isoforms. We conclude that OASL acts as a cellular antiviral protein and that RSV NS1 suppresses this function to evade cellular innate immunity and allow virus growth. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

PubMed

Malasao, Rungnapa; Okamoto, Michiko; Chaimongkol, Natthawan; Imamura, Tadatsugu; Tohma, Kentaro; Dapat, Isolde; Dapat, Clyde; Suzuki, Akira; Saito, Mayuko; Saito, Mariko; Tamaki, Raita; Pedrera-Rico, Gay Anne Granada; Aniceto, Rapunzel; Quicho, Reynaldo Frederick Negosa; Segubre-Mercado, Edelwisa; Lupisan, Socorro; Oshitani, Hitoshi

2015-01-01

Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05) and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013

PubMed Central

Malasao, Rungnapa; Okamoto, Michiko; Chaimongkol, Natthawan; Imamura, Tadatsugu; Tohma, Kentaro; Dapat, Isolde; Dapat, Clyde; Suzuki, Akira; Saito, Mayuko; Saito, Mariko; Tamaki, Raita; Pedrera-Rico, Gay Anne Granada; Aniceto, Rapunzel; Quicho, Reynaldo Frederick Negosa; Segubre-Mercado, Edelwisa; Lupisan, Socorro; Oshitani, Hitoshi

2015-01-01

Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05) and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines. PMID:26540236

Caveolae provide a specialized membrane environment for respiratory syncytial virus assembly

PubMed Central

Nguyen, Tra Huong; Leong, Daniel; Ravi, Laxmi Iyer; Tan, Boon Huan; Sandin, Sara; Sugrue, Richard J.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) is an enveloped virus that assembles into filamentous virus particles on the surface of infected cells. Morphogenesis of RSV is dependent upon cholesterol-rich (lipid raft) membrane microdomains, but the specific role of individual raft molecules in RSV assembly is not well defined. Here, we show that RSV morphogenesis occurs within caveolar membranes and that both caveolin-1 and cavin-1 (also known as PTRF), the two major structural and functional components of caveolae, are actively recruited to and incorporated into the RSV envelope. The recruitment of caveolae occurred just prior to the initiation of RSV filament assembly, and was dependent upon an intact actin network as well as a direct physical interaction between caveolin-1 and the viral G protein. Moreover, cavin-1 protein levels were significantly increased in RSV-infected cells, leading to a virus-induced change in the stoichiometry and biophysical properties of the caveolar coat complex. Our data indicate that RSV exploits caveolae for its assembly, and we propose that the incorporation of caveolae into the virus contributes to defining the biological properties of the RSV envelope. PMID:28154158

Human respiratory syncytial virus genomic and antigenic variants isolated in two hospitals during one epidemic, in Santiago, Chile.

PubMed

Luchsinger, Vivian; Noy, Andrea Elgueta; Avendaño, Luis F

2008-07-01

Human respiratory syncytial virus (HRSV) is a major cause of severe lower respiratory tract infection (LRI) in children. Distinct variants of the viruses have been described. The objective was to compare the antigenic and genetic variability of HRSV strains recovered from infants admitted to two hospitals during one epidemic in a big city. We analyzed nasopharyngeal aspirates from 201 infants admitted for LRI to two hospitals during 2002 in Santiago, Chile. The analyses were carried out using a panel of monoclonal antibodies against G glycoprotein epitopes (EIA) and RFLP for N and G genes. No differences in HRSV groups A/B and in N patterns distribution were observed among both hospitals. On the contrary, antigenic and genetic G patterns displayed a wide diversity of strains circulating during one epidemic, in one big city. RSV variability assessment depended rather on the tool used for analysis than on the geographical location.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment

PubMed Central

Griffiths, Cameron

2016-01-01

SUMMARY Respiratory syncytial virus (RSV) infection is a significant cause of hospitalization of children in North America and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. Despite its global impact on human health, there are relatively few therapeutic options available to prevent or treat RSV infection. Paradoxically, there is a very large volume of information that is constantly being refined on RSV replication, the mechanisms of RSV-induced pathology, and community transmission. Compounding the burden of acute RSV infections is the exacerbation of preexisting chronic airway diseases and the chronic sequelae of RSV infection. A mechanistic link is even starting to emerge between asthma and those who suffer severe RSV infection early in childhood. In this article, we discuss developments in the understanding of RSV replication, pathogenesis, diagnostics, and therapeutics. We attempt to reconcile the large body of information on RSV and why after many clinical trials there is still no efficacious RSV vaccine and few therapeutics. PMID:27903593

The Small Hydrophobic Protein of the Human Respiratory Syncytial Virus Forms Pentameric Ion Channels*

PubMed Central

Gan, Siok-Wan; Tan, Edward; Lin, Xin; Yu, Dejie; Wang, Juejin; Tan, Gregory Ming-Yeong; Vararattanavech, Ardcharaporn; Yeo, Chiew Ying; Soon, Cin Huang; Soong, Tuck Wah; Pervushin, Konstantin; Torres, Jaume

2012-01-01

The small hydrophobic (SH) protein is encoded by the human respiratory syncytial virus. Its absence leads to viral attenuation in the context of whole organisms, and it prevents apoptosis in infected cells. Herein, we have examined the structure of SH protein in detergent micelles and in lipid bilayers, by solution NMR and attenuated total reflection-Fourier transform infrared spectroscopy, respectively. We found that SH protein has a single α-helical transmembrane domain and forms homopentamers in several detergents. In detergent micelles, the transmembrane domain is flanked N-terminally by an α-helix that forms a ring around the lumen of the pore and C-terminally by an extended β-turn. SH protein was found in the plasma membrane of transiently expressing HEK 293 cells, which showed pH-dependent (acid-activated) channel activity. Channel activity was abolished in mutants lacking both native His residues, His22 and His51, but not when either His was present. Herein, we propose that the pentameric model of SH protein presented is a physiologically relevant conformation, albeit probably not the only one, in which SH contributes to RSV infection and replication. Viroporins are short (∼100 amino acids) viral membrane proteins that form oligomers of a defined size, act as proton or ion channels, and in general enhance membrane permeability in the host. However, with some exceptions, their precise biological role of their channel activity is not understood. In general, viroporins resemble poorly specialized proteins but are nevertheless critical for viral fitness. In vivo, viruses lacking viroporins usually exhibit an attenuated or weakened phenotype, altered tropism, and diminished pathological effects. We have chosen to study the SH protein, 64 amino acids long, found in the human respiratory syncytial virus because of the effect of RSV on human health and the lack of adequate antivirals. We show that SH protein forms oligomers that behave as ion channels when

A case of ulcerative colitis complicated with bronchiolitis obliterans organizing pneumonia (BOOP) and air leak syndrome.

PubMed

Aydoğdu, Müge; Gürsel, Gül; Özyilmaz, Ezgi; Akyürek, Nalan; Memış, Leyla

2012-01-01

Extraintestinal manifestations of inflammatory bowel diseases are well recognized and mainly affect the joints, skin, liver, and eyes; however, clinically significant pulmonary involvement is very rare. Early identification of pulmonary involvement is important and will be life-saving. We report herein a case of an ulcerative colitis patient, presenting with acute respiratory distress syndrome and bilateral recurring pneumothorax, pneumomediastinum and subcutaneous emphysema, i.e., air leak syndrome. He was diagnosed with open lung biopsy as bronchiolitis obliterans organizing pneumonia most probably due to viral etiology and responded well to steroid therapy, with almost complete resolution of radiographic and clinical findings. In inflammatory bowel disease patients, bronchiolitis obliterans organizing pneumonia developing due to viral or fungal infectious etiology or due to the inflammatory bowel disease itself may progress to acute respiratory distress syndrome and may present with air leak syndrome. Early detection is important and life-saving, since bronchiolitis obliterans organizing pneumonia often responds well to steroid treatment provided an infectious etiology has been excluded or adequate antimicrobial therapy has already been initiated.

Risk factors of respiratory syncytial virus infection among pediatric influenza-like illness and severe acute respiratory infections in Suzhou, China.

PubMed

Huang, Yukai; Hua, Jun; Wang, Dan; Chen, Liling; Zhang, Jun; Zhu, Hong; Tian, Jianmei; Zhang, Tao; Zhao, Genming

2018-03-01

The characteristics and risk factors of respiratory syncytial virus (RSV) infection among children has not yet been fully understood. To address the characteristics of RSV-associated illness and risk factors of RSV infection among children under 5 years of age in Suzhou, China. From April 2011 to March 2014, we conducted a prospective surveillance among children in Suzhou, China. Nasal or throat swabs were collected from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory infections (SARI). RSV was detected by reverse-transcriptase polymerase chain reaction and direct fluorescent antibody assay for children with ILI and SARI, respectively. Multivariable logistic-regression models were constructed to explore risk factors and symptoms of RSV infection. Of 3267 ILI and 1838 SARI children enrolled in the study, 192 (5.9%) and 287 (15.6%) tested positive for RSV, respectively. Among ILI patients, children with RSV infections visited clinics more often (P = 0.005) and had longer duration of fever (P = 0.032) than those without RSV infection. All RSV-positive children had an increased risk of having cough (OR = 2.9), rhinorrhea (OR = 1.6), breathing difficulty (OR = 3.4), wheezing (OR = 3.3), and irritability (OR = 2.7). Children aged <2 years, had history of prematurity (OR = 2.0) and recent respiratory infections (OR = 1.3) were more likely to get infected by RSV. Children with SARI had higher positive rate of RSV than those with ILI. Cough, rhinorrhea, and wheezing were the most common symptoms in RSV infection. Children aged <2 years, had history of prematurity and recent respiratory infections were the potential risk factors for RSV infection. © 2017 Wiley Periodicals, Inc.

Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection

NASA Astrophysics Data System (ADS)

Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi

2016-01-01

Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition

Molecular epidemiology of the SH (small hydrophobic) gene of human respiratory syncytial virus (HRSV), over 2 consecutive years.

PubMed

Lima, Hildenêr Nogueira; Botosso, Viviane Fongaro; Oliveira, Danielle Bruna Leal; Campos, Angélica Cristine de Almeida; Leal, Andrea Lima; Silva, Tereza Souza; Bosso, Patrícia Alves Ramos; Moraes, Claudia Trigo Pedroso; Filho, Claudionor Gomes da Silva; Vieira, Sandra Elisabete; Gilio, Alfredo Elias; Stewien, Klaus Eberhard; Durigon, Edison Luiz

2012-01-01

Human respiratory syncytial virus (HRSV) strains were isolated from nasopharyngeal aspirates collected from 965 children between 2004 and 2005, yielding 424 positive samples. We sequenced the small hydrophobic protein (SH) gene of 117 strains and compared them with other viruses identified worldwide. Phylogenetic analysis showed a low genetic variability among the isolates but allowed us to classify the viruses into different genotypes for both groups, HRSVA and HRSVB. It is also shown that the novel BA-like genotype was well segregated from the others, indicating that the mutations are not limited to the G gene. Copyright © 2011 Elsevier B.V. All rights reserved.

Adherence to Palivizumab for Respiratory Syncytial Virus Prevention in the Canadian Registry of Palivizumab.

PubMed

Chan, Parco; Li, Abby; Paes, Bosco; Abraha, Haben; Mitchell, Ian; Lanctôt, Krista L

2015-12-01

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants. Palivizumab, a means of passive prophylaxis, relies on patient adherence to ensure therapeutic effectiveness. The objective of this study is to evaluate the association between adherence and the incidence of RSV-associated outcomes and to identify demographic factors that may impact adherence. Infants were recruited into the Canadian registry of palivizumab (CARESS) with parental consent. Monthly interviews collected information on palivizumab administration and RSV-associated outcomes. An infant was considered adherent if they received all of their expected injections or ≥5 injections within the appropriate interdose intervals. Nineteen thousand two hundred thirty-five infants received a total of 83,447 injections from October 2005 to May 2014. Adherence was more likely in infants with higher maternal education and in those with siblings. Adherence was less likely in infants of aboriginal descent, with mothers who smoke and older infants. Adherence was significantly associated [odds ratio (95% confidence interval), P value] with a lower incidence of RSV infection [0.74 (0.60-0.93), 0.01] but not with RSV-associated hospitalization. However, in those hospitalized for RSV, adherence was significantly associated with the incidence of intubation and duration of hospitalization, intensive care stay and respiratory support. Adherence may have implications in children with less severe RSV infections and those who are already hospitalized for a RSV infection. Our study also identifies subpopulations that are more likely to be nonadherent to palivizumab therapy. Future studies should aim to validate the relationship among adherence, palivizumab levels and RSV-associated outcomes.

Respiratory Syncytial Virus Infection-associated Hospitalization Rates in Infants and Children With Cystic Fibrosis.

PubMed

Metz, Jakob; Eber, Ernst; Resch, Bernhard

2017-06-01

Infections with respiratory syncytial virus (RSV) are the leading cause for hospital admissions in infants and young children. The incidence of RSV-related hospitalizations in patients with cystic fibrosis (CF) is unclear. To date, no effective treatment for RSV infections is available. Thus, prophylaxis with the monoclonal antibody palivizumab is an important option. In a retrospective, single-center study at the Department of Pediatrics and Adolescent Medicine of the Medical University Graz, Austria, we analyzed all CF patients born between 1995 and 2012, who were admitted for respiratory problems between 1995 and 2014. We also defined a group of hypothetical RSV infections with the following criteria: admission caused by a respiratory infection during the first RSV season of life when no test for RSV was performed. Furthermore, we assessed the effectiveness of palivizumab as a prevention of RSV-related hospitalizations. A total of 51 patients with CF were identified. The RSV-related hospitalization rate for the first RSV season was 0. Two patients (3.9%) were hospitalized 3 and 4 times, respectively, caused by RSV infections. The mean age at the time of admission was 12.4 ± 2.5 years. One case (1.9%) met our criteria for hypothetical RSV infections. There was no difference in RSV-related hospitalization rates between patients who received palivizumab and those who did not. We found a low rate of RSV-related hospitalizations and could not demonstrate a benefit of palivizumab prophylaxis regarding a decrease of RSV-related hospital admissions. The role of RSV reinfections in CF patients beyond infancy appears to be underestimated.

Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field.

PubMed

Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A

2018-03-01

Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.

Molecular Characterization of Respiratory Syncytial Virus in Children with Repeated Infections with Subgroup B in the Philippines.

PubMed

Okamoto, Michiko; Dapat, Clyde P; Sandagon, Ann Marie D; Batangan-Nacion, Leilanie P; Lirio, Irene C; Tamaki, Raita; Saito, Mayuko; Saito-Obata, Mariko; Lupisan, Socorro P; Oshitani, Hitoshi

2018-05-02

Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes. We conducted a cohort study for children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between prior and subsequent RSV infections. We examined 1,802 children from May 2014 to January 2016 and collected 3,471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein. Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

The Human Respiratory Syncytial Virus Nonstructural Protein 1 Regulates Type I and Type II Interferon Pathways*

PubMed Central

Hastie, Marcus L.; Headlam, Madeleine J.; Patel, Nirav B.; Bukreyev, Alexander A.; Buchholz, Ursula J.; Dave, Keyur A.; Norris, Emma L.; Wright, Cassandra L.; Spann, Kirsten M.; Collins, Peter L.; Gorman, Jeffrey J.

2012-01-01

Respiratory syncytial viruses encode a nonstructural protein (NS1) that interferes with type I and III interferon and other antiviral responses. Proteomic studies were conducted on human A549 type II alveolar epithelial cells and type I interferon-deficient Vero cells (African green monkey kidney cells) infected with wild-type and NS1-deficient clones of human respiratory syncytial virus to identify other potential pathway and molecular targets of NS1 interference. These analyses included two-dimensional differential gel electrophoresis and quantitative Western blotting. Surprisingly, NS1 was found to suppress the induction of manganese superoxide dismutase (SOD2) expression in A549 cells and to a much lesser degree Vero cells in response to infection. Because SOD2 is not directly inducible by type I interferons, it served as a marker to probe the impact of NS1 on signaling of other cytokines known to induce SOD2 expression and/or indirect effects of type I interferon signaling. Deductive analysis of results obtained from cell infection and cytokine stimulation studies indicated that interferon-γ signaling was a potential target of NS1, possibly as a result of modulation of STAT1 levels. However, this was not sufficient to explain the magnitude of the impact of NS1 on SOD2 induction in A549 cells. Vero cell infection experiments indicated that NS1 targeted a component of the type I interferon response that does not directly induce SOD2 expression but is required to induce another initiator of SOD2 expression. STAT2 was ruled out as a target of NS1 interference using quantitative Western blot analysis of infected A549 cells, but data were obtained to indicate that STAT1 was one of a number of potential targets of NS1. A label-free mass spectrometry-based quantitative approach is proposed as a means of more definitive identification of NS1 targets. PMID:22322095

Impact of hospitalizations for bronchiolitis in preterm infants on long-term health care costs in Italy: a retrospective case-control study.

PubMed

Roggeri, Daniela Paola; Roggeri, Alessandro; Rossi, Elisa; Cataudella, Salvatore; Martini, Nello

2016-01-01

Bronchiolitis is an acute inflammatory injury of the bronchioles, and is the most frequent cause of hospitalization for lower respiratory tract infections in preterm infants. This was a retrospective, observational, case-control study conducted in Italy, based on administrative database analysis. The aim of this study was to evaluate differences in health care costs of preterm infants with and without early hospitalization for bronchiolitis. Preterm infants born in the period between January 1, 2009 and December 31, 2010 and hospitalized for bronchiolitis in the first year of life were selected from the ARNO Observatory database and observed for the first 4 years of life. These preterm infants were compared (paired 1-3) with preterm infants who were not hospitalized for bronchiolitis in the first year of life and with similar characteristics. Only direct health care costs reimbursed by the Italian National Health Service were considered for this study (drugs, hospitalizations, and diagnostic/therapeutic procedures). Of 40,823 newborns in the accrual period, 863 were preterm with no evidence of prophylaxis, and 22 preterm infants were hospitalized for bronchiolitis (cases) and paired with 62 controls. Overall, cases had 74% higher average cost per infant in the first 4 years of life than controls (18,624€ versus 10,189€, respectively). The major cost drivers were hospitalizations, accounting for >90% in both the populations. The increase in total yearly health care cost between cases and controls remained substantial even in the fourth year of life for all cost items. A relevant increase in hospitalizations and drug consumption linked to respiratory tract diseases was noted in infants hospitalized for bronchiolitis during the entire follow-up period. Preterm infants hospitalized for bronchiolitis in the first year of life were associated with increased resource consumption and costs throughout the entire period of observation; even in the fourth year, the

Respiratory viruses in young South African children with acute lower respiratory infections and interactions with HIV.

PubMed

Annamalay, Alicia A; Abbott, Salome; Sikazwe, Chisha; Khoo, Siew-Kim; Bizzintino, Joelene; Zhang, Guicheng; Laing, Ingrid; Chidlow, Glenys R; Smith, David W; Gern, James; Goldblatt, Jack; Lehmann, Deborah; Green, Robin J; Le Souëf, Peter N

2016-08-01

Human rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown. To describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa. Nasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses. Respiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01). RV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis. Copyright © 2016 Elsevier B.V. All rights reserved.

2′-5′-Oligoadenylate Synthetase-Like Protein Inhibits Respiratory Syncytial Virus Replication and Is Targeted by the Viral Nonstructural Protein 1

PubMed Central

Dhar, Jayeeta; Cuevas, Rolando A.; Goswami, Ramansu; Zhu, Jianzhong

2015-01-01

2′-5′-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein. Here we describe differential inhibitory activities of human OASL and the two mouse OASL homologs against respiratory syncytial virus (RSV) replication. Interestingly, nonstructural protein 1 (NS1) of RSV promoted proteasome-dependent degradation of specific OASL isoforms. We conclude that OASL acts as a cellular antiviral protein and that RSV NS1 suppresses this function to evade cellular innate immunity and allow virus growth. PMID:26178980

Multicenter Clinical Evaluation of the Alere i Respiratory Syncytial Virus Isothermal Nucleic Acid Amplification Assay.

PubMed

Hassan, Ferdaus; Hays, Lindsay M; Bonner, Aleta; Bradford, Bradley J; Franklin, Ruffin; Hendry, Phyllis; Kaminetsky, Jed; Vaughn, Michael; Cieslak, Kristin; Moffatt, Mary E; Selvarangan, Rangaraj

2018-03-01

The Alere i respiratory syncytial virus (RSV) assay is an isothermal nucleic acid amplification test capable of detecting RSV directly from respiratory specimens, with results being available in ≤13 min after test initiation. The objective of this study was to evaluate the performance characteristics of the Alere i RSV assay in a point-of-care setting by using direct nasopharyngeal (NP) swab specimens (direct NP) and nasopharyngeal swab specimens eluted and transported in viral transport medium (VTM NP). The study was a prospective, multicenter, clinical trial conducted at 9 sites across the United States to evaluate the clinical performance of the Alere i RSV assay with respiratory specimens obtained from both children (age, <18 years) and older adults (age, >60 years). The performance of the Alere i RSV assay was compared with that of the reference method, the Prodesse ProFlu+ real-time reverse transcriptase PCR (RT-PCR) assay. All specimens with discrepant test results were tested further by a second FDA-cleared PCR assay (the Verigene respiratory virus plus nucleic acid test; Luminex Inc., TX). A total of 554 subjects with signs and symptoms of respiratory infections were enrolled, and respiratory samples were collected in this study. In comparison with the ProFlu+ real-time RT-PCR, the overall sensitivity and specificity of Alere i RSV assay for the detection of RSV were 98.6% (95% confidence interval [CI], 94.4 to 99.7%) and 98.0% (95% CI, 95.8 to 99.1%), respectively, for direct NP and 98.6% (95% CI, 94.4 to 99.7%) and 97.8% (95% CI, 95.5 to 98.9%), respectively, for VTM NP. The Alere i RSV is a highly sensitive and specific molecular assay ideal for rapid RSV detection in patients in the point-of-care setting due to its minimal hands-on time and rapid result availability. Copyright © 2018 American Society for Microbiology.

Clinical and epidemiological characteristics of acute respiratory virus infections in Vietnamese children.

PubMed

Tran, D N; Trinh, Q D; Pham, N T K; Vu, M P; Ha, M T; Nguyen, T Q N; Okitsu, S; Hayakawa, S; Mizuguchi, M; Ushijima, H

2016-02-01

Information about viral acute respiratory infections (ARIs) is essential for prevention, diagnosis and treatment, but it is limited in tropical developing countries. This study described the clinical and epidemiological characteristics of ARIs in children hospitalized in Vietnam. Nasopharyngeal samples were collected from children with ARIs at Ho Chi Minh City Children's Hospital 2 between April 2010 and May 2011 in order to detect respiratory viruses by polymerase chain reaction. Viruses were found in 64% of 1082 patients, with 12% being co-infections. The leading detected viruses were human rhinovirus (HRV; 30%), respiratory syncytial virus (RSV; 23·8%), and human bocavirus (HBoV; 7·2%). HRV was detected all year round, while RSV epidemics occurred mainly in the rainy season. Influenza A (FluA) was found in both seasons. The other viruses were predominant in the dry season. HRV was identified in children of all age groups. RSV, parainfluenza virus (PIV) 1, PIV3 and HBoV, and FluA were detected predominantly in children aged 24 months, respectively. Significant associations were found between PIV1 with croup (P < 0·005) and RSV with bronchiolitis (P < 0·005). HBoV and HRV were associated with hypoxia (P < 0·05) and RSV with retraction (P < 0·05). HRV, RSV, and HBoV were detected most frequently and they may increase the severity of ARIs in children.

[Clinical signs of dysphagia in infants with acute viral bronchiolitis].

PubMed

Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

2014-09-01

To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

[Prediction of Severe Course in Infants with RSV Bronchiolitis under 6 Months. Spain].

PubMed

Ramos-Fernández, José Miguel; Moreno-Pérez, David; Gutiérrez-Bedmar, Mario; Hernández-Yuste, Alexandra; Cordón-Martínez, Ana María; Milano-Manso, Guillermo; Urda-Cardona, Antonio

2017-01-19

The need for mechanical ventilation (MV) in acute bronchiolitis (AB) by respiratory syncytial virus (RSV) varies depending on the series (6-18%). Our goal is to determine the admissions to PICU for MV in patients under 6 months with AB and define the risk factors for building a prediction model. Retrospective study of patients younger than 6 months admitted by BA-VRS between the periods April 1, 2010 and March 31, 2015 was made. The primary variable was the admission to PICU for MV. Related addition, to find risk factors in a model of binary logistic regression clinical variables were collected. A ROC curve model was developed and optimal cutoff point was identified. In 695 cases, the need of MV in the PICU (Y) was 56 (8.1%). Risk factors (Xi) included in the equation were: 1. male sex (OR 4.27) 2. postmenstrual age (OR: 0.76) 3. Weight income less than p3 (OR: 5.53) 4. intake lees than 50% (OR: 12.4) 5. Severity by scale (OR: 1.58) 6. apneas before admission (OR: 25.5) 7. bacterial superinfection (OR 5.03) and 8. gestational age more than 37 weeks OR (0.32). The area under the curve, sensitivity and specificity were 0.943, 0.84 and 0.93 respectively. The PICU admission for MV was 8.1 in every 100 healthy infants hospitalized for AB and year. The prediction model equation can help to predict patients at increased risk of severe evolution.

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

PubMed Central

Goodwin, Eileen; Gilman, Morgan S. A.; Wrapp, Daniel; Chen, Man; Ngwuta, Joan O.; Moin, Syed M.; Bai, Patricia; Sivasubramanian, Arvind; Connor, Ruth I.; Wright, Peter F.; Graham, Barney S.; McLellan, Jason S.; Walker, Laura M.

2018-01-01

SUMMARY Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated over 450 RSV fusion glycoprotein (F)-specific antibodies from seven RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naïve B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines. PMID:29396163

Children with Down syndrome are high-risk for severe respiratory syncytial virus disease.

PubMed

Stagliano, David R; Nylund, Cade M; Eide, Matilda B; Eberly, Matthew D

2015-03-01

To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity. A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization. The study included 633 200 children and 3 209 378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001). Down syndrome is independently associated with an increased risk for RSV hospitalization. Children with Down syndrome are older at time of RSV hospitalization and have more severe RSV illness than children without Down syndrome. This increased risk for hospitalization continues beyond 24 months. Published by Elsevier Inc.

Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection.

PubMed

Chen, Lan; Song, Weifeng; Davis, Ian C; Shrestha, Kedar; Schwiebert, Erik; Sullender, Wayne M; Matalon, Sadis

2009-05-01

We investigated the mechanisms by which respiratory syncytial virus (RSV) infection decreases vectorial Na+ transport across respiratory epithelial cells. Mouse tracheal epithelial (MTE) cells from either BALB/c or C57BL/6 mice and human airway H441 cells were grown on semipermeable supports under an air-liquid interface. Cells were infected with RSV-A2 and mounted in Ussing chambers for measurements of short-circuit currents (I(sc)). Infection with RSV for 24 hours (multiplicity of infection = 1) resulted in positive immunofluorescence for RSV antigen in less than 10% of MTE or H441 cells. In spite of the limited number of cells infected, RSV reduced both basal and amiloride-sensitive I(sc) in both MTE and H441 cells by approximately 50%, without causing a concomitant reduction in transepithelial resistance. Agents that increased intracellular cAMP (forskolin, cpt-CAMP, and IBMX) increased mainly Cl(-) secretion in MTE cells and Na+ absorption in H441 cells. RSV infection for 24 hours blunted both variables. In contrast, ouabain sensitive I(sc), measured across apically permeabilized H441 monolayers, remained unchanged. Western blot analysis of H441 cell lysates demonstrated reductions in alpha- but not gamma-ENaC subunit protein levels at 24 hours after RSV infection. The reduction in amiloride-sensitive I(sc) in H441 cells was prevented by pretreatment with inhibitors of de novo pyrimidine or purine synthesis (A77-1726 and 6-MP, respectively, 50 microM). Our results suggest that infection of both murine and human respiratory epithelial cells with RSV inhibits vectorial Na+ transport via nucleotide release. These findings are consistent with our previous studies showing reduced alveolar fluid clearance after RSV infection of BALB/c mice.

Genetic diversity of human respiratory syncytial virus circulating among children in Ibadan, Nigeria.

PubMed

Ogunsemowo, Olukunle; Olaleye, David O; Odaibo, Georgina N

2018-01-01

Human respiratory syncytial virus (HRSV) is the most common viral cause of acute lower respiratory tract infections (LRTIs) in infants and young children however, without an effective vaccine licensed for human use till date. Information on the circulating genotypes of HRSV from regions with high-burden of infection is vital in the global efforts towards the development of protective vaccine. We report here the genotypes of HRSV circulating among children in Ibadan, the first of such from Nigeria.Nasopharyngeal and oropharyngeal swabs collected from 231 children presenting with respiratory infections in some health facilities for care as well as those attending immunization centers for routine vaccination in Ibadan, Nigeria were used for the study. The 2nd hypervariable (HVR2) region of the glycoprotein (G) gene of HRSV was amplified and sequenced using HRSV group specific primers. HRSV was detected in 41 out of the 231 samples. Thirty-three of the isolates were successfully subtyped(22 subtype A and 11 subtype B). Fourteen of the subtype A and all the subtype B were successfully sequenced and genotyped. Phylogenetic analysis showed that genotype ON1 with 72 nucleotide (nt) duplication was the major subgroup A virus (11 of 14) detected together with genotype NA2. All the HRSV subtype B detected belong to the BA genotype with characteristic 60nt duplication. The ON1 genotypes vary considerably from the prototype strain due to amino acid substitutions including T292I which has not been reported elsewhere. The NA2 genotypes have mutations on four antigenic sites within the HVR2relative to the prototype A2. In conclusion, three genotypes of HRSV were found circulating in Ibadan, Nigeria. Additional study that will include isolates from other parts of the country will be done to determine the extent of genotype diversity of HRSV circulating in Nigeria.

Modifiable risk factors associated with bronchiolitis

PubMed Central

Nenna, Raffaella; Cutrera, Renato; Frassanito, Antonella; Alessandroni, Claudia; Nicolai, Ambra; Cangiano, Giulia; Petrarca, Laura; Arima, Serena; Caggiano, Serena; Ullmann, Nicola; Papoff, Paola; Bonci, Enea; Moretti, Corrado; Midulla, Fabio

2017-01-01

Background: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. Methods: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5–12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5–36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at ‘Sapienza’ University Rome and IRCCS Bambino Gesù Hospital. Infants’ parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers. Results: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2–3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7–4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1–2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2–2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls (p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. Conclusions: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures – for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke

Using Mathematical Transmission Modelling to Investigate Drivers of Respiratory Syncytial Virus Seasonality in Children in the Philippines

PubMed Central

Paynter, Stuart; Yakob, Laith; Simões, Eric A. F.; Lucero, Marilla G.; Tallo, Veronica; Nohynek, Hanna; Ware, Robert S.; Weinstein, Philip; Williams, Gail; Sly, Peter D.

2014-01-01

We used a mathematical transmission model to estimate when ecological drivers of respiratory syncytial virus (RSV) transmissibility would need to act in order to produce the observed seasonality of RSV in the Philippines. We estimated that a seasonal peak in transmissibility would need to occur approximately 51 days prior to the observed peak in RSV cases (range 49 to 67 days). We then compared this estimated seasonal pattern of transmissibility to the seasonal patterns of possible ecological drivers of transmissibility: rainfall, humidity and temperature patterns, nutritional status, and school holidays. The timing of the seasonal patterns of nutritional status and rainfall were both consistent with the estimated seasonal pattern of transmissibility and these are both plausible drivers of the seasonality of RSV in this setting. PMID:24587222

M Protein-Deficient Respiratory Syncytial Virus (RSV) Vaccine Protects Infant Baboons Against RSV Challenge

PubMed Central

Welliver, Robert C; Oomens, Antonius; Wolf, Roman; Papin, James; Ivanov, Vadim; Preno, Alisha; Staats, Rachel; Piedra, Pedro; Yu, Zhongxin

2017-01-01

Abstract Background RSV bronchiolitis is the most common cause of hospitalization of infants in the US, and may lead to the development of long-term airway disease. Inactivated vaccines may lead to enhanced disease, while replicating vaccines have caused unacceptable degrees of illness, and may revert back to wild type. We developed an RSV vaccine lacking the gene for the M protein (Mnull RSV). The M protein is responsible for reassembly of the virus after it infects cells and expresses its proteins. Infant baboons vaccinated intranasally (IN) with Mnull RSV develop serum neutralizing antibody (NA) responses, but the virus does not replicate. Methods 2-week-old baboons (n = 12) were primed IN with 107 vaccine units of Mnull RSV or a control preparation, and a similar booster dose was given 4 weeks later. Mnull RSV vaccination did not cause tachypnea, airway inflammation or other signs of illness when compared with sham-vaccinated controls. Two weeks after boosting, all infants were challenged intratracheally with human RSV A2. We continuously monitored respiratory rates and levels of overall activity. On various days following challenge, we obtained BAL fluids for leukocyte counts and degree of virus replication, and evaluated alveolar-arterial oxygen gradients (A-a O2). Results Vaccinated animals (vs. unvaccinated controls) had lower respiratory rates (P = 0.0014), improved A-a O2 (P = 0.0063) and reduced viral replication (P = 0.0014). Activity scores were higher in vaccine recipients than in unvaccinated animals. Vaccine recipients also were primed for earlier serum and secretory neutralizing antibody responses, and greater airway lymphocyte responses. Airway lymphocyte numbers (but not antibody responses) were associated with lower respiratory rates and reduced viral replication (P < 0.01). Conclusion Vaccination intranasally with Mnull RSV protected infant baboons against an RSV challenge without causing respiratory disease or enhanced illness, and

Constrictive (obliterative) bronchiolitis: diagnosis, etiology, and a critical review of the literature.

PubMed

Schlesinger, C; Meyer, C A; Veeraraghavan, S; Koss, M N

1998-10-01

Constrictive bronchiolitis (CB) (or obliterative bronchiolitis) designates inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles, with resultant narrowing of their lumens. It differs from bronchiolitis obliterans-organizing pneumonia in its histopathology and clinical course. Most cases of CB occur in the setting of organ transplants, particularly lung and heart-lung transplants, but also in bone marrow transplants. Other bona fide cases are rare: infection, particularly viral infection, appears to be a well-documented precursor to CB in children, but not in immunocompetent adults. Constrictive bronchiolitis also has been reported in the course of rheumatoid arthritis, in certain other autoimmune diseases such as pemphigus vulgaris, after inhalation of toxic gases such as nitrogen oxide, after ingestion of certain drugs or medicinal agents such as Sauropus androgynous, and as a cryptogenic illness. Recent reports suggest that CB, as defined by clinical criteria (that is, bronchiolitis obliterans syndrome), is very common in lung allograft recipients who survive more than 5 years and, although it is associated with significant mortality, it also can be clinically stable. Furthermore, with the current practice of close monitoring of these patients, it appears that CB may now be diagnosed at an earlier stage, at which resolution, or at least stabilization of progression, is possible. A histopathologic diagnosis of CB in lung transplant and other patients may be difficult to make due to the patchy distribution of lesions, the technical difficulty in obtaining tissue in late lesions with extensive fibrosis, and the failure to recognize lesions. With regard to the last of these, in early stages of disease, CB may be subtle and easily missed in routine hematoxylin-eosin-stained specimens, while in advanced stages the disease may be equally difficult to diagnose if the patchy scarring in the lung is

Associations of Nasopharyngeal Metabolome and Microbiome with Severity among Infants with Bronchiolitis. A Multiomic Analysis.

PubMed

Stewart, Christopher J; Mansbach, Jonathan M; Wong, Matthew C; Ajami, Nadim J; Petrosino, Joseph F; Camargo, Carlos A; Hasegawa, Kohei

2017-10-01

Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity. To determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis. We conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation). Nasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae. Although further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.

Phylogeny and population dynamics of respiratory syncytial virus (Rsv) A and B.

PubMed

Martinelli, Marianna; Frati, Elena Rosanna; Zappa, Alessandra; Ebranati, Erika; Bianchi, Silvia; Pariani, Elena; Amendola, Antonella; Zehender, Gianguglielmo; Tanzi, Elisabetta

2014-08-30

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children. RSV is characterised by high variability, especially in the G glycoprotein, which may play a significant role in RSV pathogenicity by allowing immune evasion. To reconstruct the origin and phylodynamic history of RSV, we evaluated the genetic diversity and evolutionary dynamics of RSV A and RSV B isolated from children under 3 years old infected in Italy from 2006 to 2012. Phylogenetic analysis revealed that most of the RSV A sequences clustered with the NA1 genotype, and RSV B sequences were included in the Buenos Aires genotype. The mean evolutionary rates for RSV A and RSV B were estimated to be 2.1 × 10(-3) substitutions (subs)/site/year and 3.03 × 10(-3) subs/site/year, respectively. The time of most recent common ancestor for the tree root went back to the 1940s (95% highest posterior density-HPD: 1927-1951) for RSV A and the 1950s (95%HPD: 1951-1960) for RSV B. The RSV A Bayesian skyline plot (BSP) showed a decrease in transmission events ending in about 2005, when a sharp growth restored the original viral population size. RSV B BSP showed a similar trend. Site-specific selection analysis identified 10 codons under positive selection in RSV A sequences and only one site in RSV B sequences. Although RSV remains difficult to control due to its antigenic diversity, it is important to monitor changes in its coding sequences, to permit the identification of future epidemic strains and to implement vaccine and therapy strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

PubMed Central

Agnes, J. T.; Zekarias, B.; Shao, M.; Anderson, M. L.; Gershwin, L. J.

2013-01-01

Our previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSV-plus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection. PMID:23649093

Bovine respiratory syncytial virus and Histophilus somni interaction at the alveolar barrier.

PubMed

Agnes, J T; Zekarias, B; Shao, M; Anderson, M L; Gershwin, L J; Corbeil, L B

2013-07-01

Our previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSV-plus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection.

Primary Sjögren's syndrome and bronchiolitis. An unusual association.

PubMed

Medina-Paz, Lourdes; Che-Morales, José Luis; Alonso Moshe Barrera-Pérez, Hirian; Cortes-Telles, Arturo

2017-03-03

Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands. It has been reported that the association between SS and respiratory involvement occurs in 11% and 45% of cases, and can be the initial manifestation of the disease. The diagnosis is based on the integration of clinical, immunological and histopathological criteria. This paper examines a 58-year-old man with SS, severe dyspnea and recurrent exacerbations associated with bronchiolitis-bronchiectasis. The absence of anti-Ro and anti-La antibodies associated with severe bronchiolitis is a clinical presentation that is poorly characterized in this group of patients; moreover, how to treat them remains unclear. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Comparison of Bovine coronavirus-specific and Bovine respiratory syncytial virus-specific antibodies in serum versus milk samples detected by enzyme-linked immunosorbent assay.

PubMed

Ohlson, Anna; Blanco-Penedo, Isabel; Fall, Nils

2014-01-01

Bovine coronavirus (BCV; Betacoronavirus 1) and Bovine respiratory syncytial virus (BRSV) are significant causes of enteric and respiratory disease in beef and dairy cattle throughout the world. Indirect enzyme-linked immunosorbent assays are widely used to detect serum antibodies for herd monitoring and prevalence studies. In dairy herds, milk is more readily collected than serum. Hence, in order to investigate the test agreement between serum and milk, both serum and milk samples from 105 cows in 27 dairy herds were analyzed in parallel for presence of immunoglobulin G antibodies to BCV and BRSV. The Bland-Altman analyses of data demonstrated good agreement between serum and milk antibody titers for both viruses. The results indicate milk samples are sufficient for surveillance of antibodies to BCV and BRSV.

Incidence of respiratory viruses in Peruvian children with acute respiratory infections.

PubMed

del Valle Mendoza, Juana; Cornejo-Tapia, Angela; Weilg, Pablo; Verne, Eduardo; Nazario-Fuertes, Ronald; Ugarte, Claudia; del Valle, Luis J; Pumarola, Tomás

2015-06-01

Acute respiratory infections are responsible for high morbi-mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses. © 2015 Wiley Periodicals, Inc.

Targeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication

PubMed Central

Bailly, B.; Richard, C.-A.; Sharma, G.; Wang, L.; Johansen, L.; Cao, J.; Pendharkar, V.; Sharma, D.-C.; Galloux, M.; Wang, Y.; Cui, R.; Zou, G.; Guillon, P.; von Itzstein, M.; Eléouët, J.-F.; Altmeyer, R.

2016-01-01

Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti-termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection. PMID:27194388

Acute viral bronchiolitis: Physician perspectives on definition and clinically important outcomes.

PubMed

Fernandes, Ricardo M; Andrade, Maria Gabriela; Constant, Carolina; Malveiro, Duarte; Magalhães, Manuel; Abreu, Daisy; Azevedo, Inês; Sousa, Eduarda; Salgado, Rizério; Bandeira, Teresa

2016-07-01

Two key limitations hamper intervention research in bronchiolitis: the absence of a clear definition of disease, and the heterogeneous choice of outcome measures in current clinical trials. We assessed how paediatricians and general practitioners (GPs) perceived definition and clinically important outcomes in bronchiolitis. A nationwide online survey (ABBA study) was conducted through the Portuguese Society of Paediatrics and GPs' mailing lists. We assessed agreement with statements on bronchiolitis definition, and participants were asked to score the relative importance of several outcomes. Principal component analysis (PCA) explored dimensions underlying disease definition. Outcomes were ranked by mean score and proportion given highest score. We included 514 paediatricians and 165 GPs (overall 59% were board-certified). Most paediatricians (76.5%) agreed with a definition based on coryza, wheezing and/or crackles/rales, compared to 38.1% GPs (P < 0.001). Less than 5% physicians agreed with a definition commonly used in clinical trials (<12 months, first episode of wheeze). We retained three dimensions on PCA: one based on coryza, rales/crepitations and no sudden onset; another on number of episodes and age; and a third on wheeze. Dimensions varied by physician specialization and training (P < 0.01). Hospital admission and respiratory distress were top rated outcomes by both groups of physicians. Physician definitions of bronchiolitis have considerable variability and often mismatch those of clinical trials. Rating of important outcomes was consistent. Our results highlight the need for a robust standardized definition of acute bronchiolitis in infants and support the development of a core outcome set for future clinical trials. Pediatr Pulmonol. 2016;51:724-732. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus.

PubMed

Salez, Nicolas; Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Charrel, Remi N

2015-04-01

A total of 281 clinical specimens (nasal swabs and nasopharyngeal aspirates) were tested with the Xpert® Flu/RSV XC. The results were compared to those obtained with the real-time retro transcriptase-polymerase chain reaction assays routinely used in our laboratory. The Xpert® Flu/RSV XC showed sensitivity/specificity of 97.8%/100% and 97.9%/100% for flu and respiratory syncytial virus, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

RNAi-dependent and -independent antiviral phenotypes of chromosomally integrated shRNA clones: role of VASP in respiratory syncytial virus growth.

PubMed

Musiyenko, Alla; Bitko, Vira; Barik, Sailen

2007-07-01

Stable RNA interference (RNAi) is commonly achieved by recombinant expression of short hairpin RNA (shRNA). To generate virus-resistant cell lines, we cloned a shRNA cassette against the phosphoprotein gene of respiratory syncytial virus (RSV) into a polIII-driven plasmid vector. Analysis of individual stable transfectants showed a spectrum of RSV resistance correlating with the levels of shRNA expressed from different chromosomal locations. Interestingly, resistance in a minority of clones was due to mono-allelic disruption of the cellular gene for vasodilator-stimulated phosphoprotein (VASP). Thus, pure clones of chromosomally integrated DNA-directed RNAi can exhibit gene disruption phenotypes resembling but unrelated to RNAi.

Oral immunization of mice with transgenic tomato fruit expressing respiratory syncytial virus-F protein induces a systemic immune response.

PubMed

Sandhu, J S; Krasnyanski, S F; Domier, L L; Korban, S S; Osadjan, M D; Buetow, D E

2000-04-01

Respiratory syncytial virus (RSV) is one of the most important pathogens of infancy and early childhood. Here a fruit-based edible subunit vaccine against RSV was developed by expressing the RSV fusion (F) protein gene in transgenic tomato plants. The F-gene was expressed in ripening tomato fruit under the control of the fruit-specific E8 promoter. Oral immunization of mice with ripe transgenic tomato fruits led to the induction of both serum and mucosal RSV-F specific antibodies. The ratio of immunoglobulin subclasses produced in response to immunization suggested that a type 1 T-helper cell immune response was preferentially induced. Serum antibodies showed an increased titer when the immunized mice were exposed to inactivated RSV antigen.

Serologic Cross-Reactions between Nucleocapsid Proteins of Human Respiratory Syncytial Virus and Human Metapneumovirus

PubMed Central

Zhang, Yange; Pohl, Jan; Brooks, W. Abdullah

2015-01-01

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥4-fold increase in titers of antibody to hRSV, 24 (25.8%) showed a concurrent increase in titers of antibody to hMPV; of 91 pairs showing an increase to hMPV, 13 (14.3%) showed a concurrent increase to hRSV. We speculated that common antigens shared by these viruses explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared for each virus against baculovirus-expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blotting, this truncated protein did not react with hMPV IgG-positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared for this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region. PMID:25740767

Serologic cross-reactions between nucleocapsid proteins of human respiratory syncytial virus and human metapneumovirus.

PubMed

Zhang, Yange; Pohl, Jan; Brooks, W Abdullah; Erdman, Dean D

2015-05-01

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥ 4-fold increase in titers of antibody to hRSV, 24 (25.8%) showed a concurrent increase in titers of antibody to hMPV; of 91 pairs showing an increase to hMPV, 13 (14.3%) showed a concurrent increase to hRSV. We speculated that common antigens shared by these viruses explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared for each virus against baculovirus-expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blotting, this truncated protein did not react with hMPV IgG-positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared for this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae; Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae; Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae

2014-04-15

We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATPmore » following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.« less

Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa.

PubMed

Salomonsen, Charlotte M; Breum, Solvej Ø; Larsen, Lars E; Jakobsen, Jeanette; Høiby, Niels; Hammer, Anne S

2012-11-26

Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found. This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates.

PubMed

Mazur, Natalie I; Higgins, Deborah; Nunes, Marta C; Melero, José A; Langedijk, Annefleur C; Horsley, Nicole; Buchholz, Ursula J; Openshaw, Peter J; McLellan, Jason S; Englund, Janet A; Mejias, Asuncion; Karron, Ruth A; Simões, Eric Af; Knezevic, Ivana; Ramilo, Octavio; Piedra, Pedro A; Chu, Helen Y; Falsey, Ann R; Nair, Harish; Kragten-Tabatabaie, Leyla; Greenough, Anne; Baraldi, Eugenio; Papadopoulos, Nikolaos G; Vekemans, Johan; Polack, Fernando P; Powell, Mair; Satav, Ashish; Walsh, Edward E; Stein, Renato T; Graham, Barney S; Bont, Louis J

2018-06-15

The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide. Copyright © 2018 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Comparison of CPAP and HFNC in Management of Bronchiolitis in Infants and Young Children.

PubMed

Pedersen, Majken Bisgaard; Vahlkvist, Signe

2017-04-20

Continuous positive airway pressure (CPAP) has been used in infants with bronchiolitis for decades. Recently, high flow nasal cannula (HFNC) therapy was introduced We conducted a retrospective study of treatment with CPAP vs. HFNC between 2013 and 2015, comparing the development in respiratory rate, fraction of inspired oxygen (FiO2) and heart rate, treatment failure, duration of treatment, and length of hospital stay. A sample size of 49 children were included. Median age was 1.9 months. Median baseline pCO₂ was 7.4 kPa in both groups, respiratory rate per minute was 57 vs. 58 (CPAP vs. HFNC). Respiratory rate decreased faster in the CPAP group ( p < 0.05). FiO2 decreased in the CPAP group and increased in the HFNC group during the first 12 h, whereafter it decreased in both groups. ( p < 0.01). Heart rate development was similar in both groups. Twelve children (55%) changed systems from HFNC to CPAP due to disease progression. There was no difference in length of treatment, hospital stay, or transmission to intensive care unit between the groups. CPAP was more effective than HFNC in decreasing respiratory rate (RR) and FiO2. No differences were observed in length of treatment or complications. Further studies should be conducted to compare the efficacy of the two treatments of bronchiolitis, preferably through prospective randomized trials.

Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector.

PubMed

Liang, Bo; Ngwuta, Joan O; Herbert, Richard; Swerczek, Joanna; Dorward, David W; Amaro-Carambot, Emerito; Mackow, Natalie; Kabatova, Barbora; Lingemann, Matthias; Surman, Sonja; Yang, Lijuan; Chen, Man; Moin, Syed M; Kumar, Azad; McLellan, Jason S; Kwong, Peter D; Graham, Barney S; Schaap-Nutt, Anne; Collins, Peter L; Munir, Shirin

2016-11-01

Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine/human PIV3 (rB/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced "high-quality" RSV-neutralizing antibodies, defined as antibodies that neutralize RSV in vitro without added complement (B. Liang et al., J Virol 89:9499-9510, 2015, doi:10.1128/JVI.01373-15). In the present study, we modified RSV F by replacing its cytoplasmic tail (CT) domain or its CT and transmembrane (TM) domains (TMCT) with counterparts from BPIV3 F, with or without pre-F stabilization. This resulted in RSV F being packaged in the rB/HPIV3 particle with an efficiency similar to that of RSV particles. Enhanced packaging was substantially attenuating in hamsters (10- to 100-fold) and rhesus monkeys (100- to 1,000-fold). Nonetheless, TMCT-directed packaging substantially increased the titers of high-quality RSV-neutralizing serum antibodies in hamsters. In rhesus monkeys, a strongly additive immunogenic effect of packaging and pre-F stabilization was observed, as demonstrated by 8- and 30-fold increases of RSV-neutralizing serum antibody titers in the presence and absence of added complement, respectively, compared to pre-F stabilization alone. Analysis of vaccine-induced F-specific antibodies by binding assays indicated that packaging conferred substantial stabilization of RSV F in the pre-F conformation. This provides an improved version of this well-tolerated RSV/HPIV3 vaccine candidate, with potently improved immunogenicity, which can be returned to clinical trials. Human respiratory syncytial virus (RSV) and

Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector

PubMed Central

Liang, Bo; Ngwuta, Joan O.; Herbert, Richard; Swerczek, Joanna; Dorward, David W.; Amaro-Carambot, Emerito; Mackow, Natalie; Kabatova, Barbora; Lingemann, Matthias; Surman, Sonja; Yang, Lijuan; Chen, Man; Moin, Syed M.; Kumar, Azad; McLellan, Jason S.; Kwong, Peter D.; Graham, Barney S.; Schaap-Nutt, Anne; Collins, Peter L.

2016-01-01

ABSTRACT Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine/human PIV3 (rB/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced “high-quality” RSV-neutralizing antibodies, defined as antibodies that neutralize RSV in vitro without added complement (B. Liang et al., J Virol 89:9499–9510, 2015, doi:10.1128/JVI.01373-15). In the present study, we modified RSV F by replacing its cytoplasmic tail (CT) domain or its CT and transmembrane (TM) domains (TMCT) with counterparts from BPIV3 F, with or without pre-F stabilization. This resulted in RSV F being packaged in the rB/HPIV3 particle with an efficiency similar to that of RSV particles. Enhanced packaging was substantially attenuating in hamsters (10- to 100-fold) and rhesus monkeys (100- to 1,000-fold). Nonetheless, TMCT-directed packaging substantially increased the titers of high-quality RSV-neutralizing serum antibodies in hamsters. In rhesus monkeys, a strongly additive immunogenic effect of packaging and pre-F stabilization was observed, as demonstrated by 8- and 30-fold increases of RSV-neutralizing serum antibody titers in the presence and absence of added complement, respectively, compared to pre-F stabilization alone. Analysis of vaccine-induced F-specific antibodies by binding assays indicated that packaging conferred substantial stabilization of RSV F in the pre-F conformation. This provides an improved version of this well-tolerated RSV/HPIV3 vaccine candidate, with potently improved immunogenicity, which can be returned to clinical trials. IMPORTANCE Human respiratory

Detection of airborne respiratory syncytial virus in a pediatric acute care clinic.

PubMed

Grayson, Stephanie A; Griffiths, Pamela S; Perez, Miriam K; Piedimonte, Giovanni

2017-05-01

Respiratory syncytial virus (RSV) is the most common cause of respiratory illness in infants and young children, but this virus is also capable of re-infecting adults throughout life. Universal precautions to prevent its transmission consist of gown and glove use, but masks and goggles are not routinely required because it is believed that RSV is unlikely to be transmitted by the airborne route. Our hypothesis was that RSV is present in respirable-size particles aerosolized by patients seen in a pediatric acute care setting. RSV-laden particles were captured using stationary 2-stage bioaerosol cyclone samplers. Aerosol particles were separated into three size fractions (<1, 1-4.1, and ≥4.1 μm) and were tested for the presence of RSV RNA by real-time PCR. Samplers were set 152 cm ("upper") and 102 cm ("lower") above the floor in each of two examination rooms. Of the total, 554 samples collected over 48 days, only 13 (or 2.3%) were positive for RSV. More than 90% of the RSV-laden aerosol particles were in the ≥4.1 μm size range, which typically settle to the ground within minutes, whereas only one sample (or 8%) was positive for particles in the 1-4.1 μm respirable size range. Our data indicate that airborne RSV-laden particles can be detected in pediatric outpatient clinics during the epidemic peak. However, RSV airborne transmission is highly inefficient. Thus, the logistical and financial implications of mandating the use of masks and goggles to prevent RSV spread seem unwarranted in this setting. Pediatr Pulmonol. 2017;52:684-688. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Real-Time Light Scattering Tracking of Gold Nanoparticles- bioconjugated Respiratory Syncytial Virus Infecting HEp-2 Cells

NASA Astrophysics Data System (ADS)

Wan, Xiao-Yan; Zheng, Lin-Ling; Gao, Peng-Fei; Yang, Xiao-Xi; Li, Chun-Mei; Li, Yuan Fang; Huang, Cheng Zhi

2014-03-01

Real-time tracking of virus invasion is crucial for understanding viral infection mechanism, which, however, needs simple and efficient labeling chemistry with improved signal-to-noise ratio. For that purpose, herein we investigated the invasion dynamics of respiratory syncytial virus (RSV) through dark-field microscopic imaging (iDFM) technique by using Au nanoparticles (AuNPs) as light scattering labels. RSV, a ubiquitous, non-segmented, pleiomorphic and negative-sense RNA virus, is an important human pathogen in infants, the elderly, and the immunocompromised. In order to label the enveloped virus of paramyxoviridae family, an efficient streptavidin (SA)-biotin binding chemistry was employed, wherein AuNPs and RSV particles modified with SA and biotin, respectively, allowing the AuNP-modified RSVs to maintain their virulence without affecting the native activities of RSV, making the long dynamic visualization successful for the RSV infections into human epidermis larynx carcinoma cells.

Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs.

PubMed

Mora, Alejandro Larios; Detalle, Laurent; Gallup, Jack M; Van Geelen, Albert; Stohr, Thomas; Duprez, Linde; Ackermann, Mark R

2018-05-07

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined: day 1-5 or day 3-5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.

Parental and household smoking and the increased risk of bronchitis, bronchiolitis and other lower respiratory infections in infancy: systematic review and meta-analysis.

PubMed

Jones, Laura L; Hashim, Ahmed; McKeever, Tricia; Cook, Derek G; Britton, John; Leonardi-Bee, Jo

2011-01-10

Passive smoke exposure increases the risk of lower respiratory infection (LRI) in infants, but the extensive literature on this association has not been systematically reviewed for nearly ten years. The aim of this paper is to provide an updated systematic review and meta-analysis of studies of the association between passive smoking and LRI, and with diagnostic subcategories including bronchiolitis, in infants aged two years and under. We searched MEDLINE and EMBASE (to November 2010), reference lists from publications and abstracts from major conference proceedings to identify all relevant publications. Random effect pooled odds ratios (OR) with 95% confidence intervals (CI) were estimated. We identified 60 studies suitable for inclusion in the meta-analysis. Smoking by either parent or other household members significantly increased the risk of LRI; odds ratios (OR) were 1.22 (95% CI 1.10 to 1.35) for paternal smoking, 1.62 (95% CI 1.38 to 1.89) if both parents smoked, and 1.54 (95% CI 1.40 to 1.69) for any household member smoking. Pre-natal maternal smoking (OR 1.24, 95% CI 1.11 to 1.38) had a weaker effect than post-natal smoking (OR 1.58, 95% CI 1.45 to 1.73). The strongest effect was on bronchiolitis, where the risk of any household smoking was increased by an OR of 2.51 (95% CI 1.96 to 3.21). Passive smoking in the family home is a major influence on the risk of LRI in infants, and especially on bronchiolitis. Risk is particularly strong in relation to post-natal maternal smoking. Strategies to prevent passive smoke exposure in young children are an urgent public and child health priority.

Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact.

PubMed

Sørup, Signe; Benn, Christine Stabell; Stensballe, Lone Graff; Aaby, Peter; Ravn, Henrik

2015-01-01

The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association was strongest for admissions with lower respiratory infections. To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. Nationwide cohort study of laboratory-confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. The study included 888 RSV hospital contacts in 128,588 person years of follow up (rate 6.8/1000 person years). Having MMR as the most recent vaccine was associated with a reduced rate of RSV hospital contacts compared with having DTaP-IPV-Hib as the most recent vaccine (Incidence rate ratio (IRR), 0.75; 95% confidence interval (CI), 0.63-0.89). After adjustment for potential confounders including exact age in days the IRR was 0.78 (95% CI, 0.66-0.93). The adjusted IRR was 0.74 (95% CI, 0.60-0.92) in males and 0.84 (95% CI, 0.66-1.06) in females (P Interaction, 0.42). There was no association in the first month after MMR vaccination (adjusted IRR, 0.97; 95% CI, 0.76-1.24) but the adjusted IRR was 0.70 (95% CI, 0.58-0.85) from one month after MMR vaccination. MMR vaccination was associated with reduced rate of hospital contacts related to laboratory-confirmed RSV infection. Further research on the association between MMR vaccination and other unrelated pathogens are warranted. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea.

PubMed

Jafri, Hasan S; Wu, Xionghua; Makari, Doris; Henrickson, Kelly J

2013-04-01

Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B. To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States. A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction. Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001). This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.

The association between gender and pediatric respiratory morbidity.

PubMed

Ben-Shmuel, Atar; Sheiner, Eyal; Wainstock, Tamar; Landau, Daniella; Vaknin, Flear; Walfisch, Asnat

2018-06-26

To evaluate the association between newborn gender and the risk for later pediatric respiratory morbidity. A population based cohort analysis was performed by comparing the risk of long-term respiratory morbidity (until 18 years of age) according to gender. Respiratory morbidity included hospitalizations involving pneumonia, asthma, bronchitis, bronchiolitis, upper respiratory tract infection (URTI), influenza, and bronchiectasis. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were constructed to compare cumulative respiratory morbidity. A Cox proportional hazards model controlled for confounders. During the study period 240 953 newborns met the inclusion criteria. Among them, 118 113 were females (49.0%) and 122 840 were males (51.0%). During the 18 years of follow-up, 13 719 (5.7%) different newborns were hospitalized with respiratory related morbidity. Males had significantly higher rates of respiratory morbidity as compared with females (6.4% vs 4.9% respectively, P < 0.001, OR 1.32, 95% CI 1.28-1.37). Specifically, pneumonia, bronchitis, asthma, bronchiolitis, and URTI were significantly more common in males. Males exhibited higher total cumulative respiratory morbidity (log rank P < 0.001), as well as higher cumulative morbidity in several sub-categories. These sub-categories included pneumonia, bronchitis, asthma, bronchiolitis, and URTI (P < 0.05 in all). The Cox regression model demonstrated male gender to be an independent risk factor for pediatric respiratory morbidity while adjusting for gestational age, birthweight, and other confounders (HR 1.29, 95% CI 1.25-1.34, P < 0.001). Males are at an increased risk for pediatric respiratory morbidity, independent of obstetrical characteristics such as gestational age and birthweight. © 2018 Wiley Periodicals, Inc.

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

PubMed Central

Stohr, Thomas; Palomo, Concepción; Piedra, Pedro A.; Gilbert, Brian E.; Mas, Vicente; Millar, Andrena; Power, Ultan F.; Stortelers, Catelijne; Allosery, Koen; Melero, José A.; Depla, Erik

2015-01-01

Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease. PMID:26438495

Influenza A virus among the hospitalized young children with acute respiratory infection. Is influenza A co infected with respiratory syncytial virus?

PubMed Central

Alavi, Seyed Mohammad; Makvandi, Manoochehr; Najafi-Fard, Saied; Alavi, Leila

2012-01-01

Background: Both influenza A virus (IAV) and respiratory syncytial virus (RSV) cause acute respiratory infection (ARI) in infants and young children. This study was conducted to determine Influenza A virus and its co infection with RSV among the hospitalized children with ARI. Methods: A total of 153 throat samples of the hospitalized young children aged between below one year and 5 years with the clinical signs of ARI were collected from the different hospitals in Khuzestan from June 2009 to April 2010. The samples were tested for Influenza A viruses by real time PCR. Positive IAV samples were tested for influenza A sub type H1N1 and for RSV by the nested PCR. Results: In this study, from the total 153 samples, 35 samples (22.9%) including 15 (42.8%) females and 20 (57.2%) males were positive for influenza A viruses. From the 35 positive samples for IAV, 14 were positive for swine H1N1 subtype. All the positive samples for influenza showed negative for RSV infection which revealed no coinfection with RSV. The prevalence of influenza A among age/sex groups was not significant. Conclusion: Influenza A is a prevalent viral agent isolated from young children with ARI. Influenza A subtype H1N1 was accounted for the 40 percent all laboratory-proven diagnoses of influenza in 2009. No evidence of coinfection of influenza A and RSV has been observed in the present study. PMID:24009929

Microscopic anatomy of the lower respiratory tract of the grey short-tailed opossum (Monodelphis domestica).

PubMed

Cope, L A; Henry, R W; Reed, R B

2012-04-01

The respiratory tracts of seven grey short-tailed opossums were histologically examined. Six opossums were prepared by perfusion with buffered formalin. Opossum seven was perfused with gluteraldehyde. Samples taken from the respiratory passages and lungs of specimens 1-6 were stained with haematoxylin and eosin. A mixture of methylene and azure blue was used for specimen 7. The trachea and right and left principal bronchi are lined with a pseudostratified ciliated columnar epithelium with occasional goblet cells. The secondary and tertiary bronchi and the primary and secondary bronchioles are lined by a simple ciliated columnar epithelium. The terminal bronchioles and a portion of the respiratory bronchioles are lined by a simple ciliated cuboidal epithelium. The terminal portion of the respiratory bronchioles and the alveolar ducts are lined with simple squamous epithelium. Alveoli are lined by type I and II pneumocytes. Tracheal glands are present in the tela submucosa. The fibromusculocartilaginous tunic of the trachea consists of c-shaped cartilage rings and the trachealis muscle. A lamina muscularis mucosa begins in the intrapulmonary portion of the principal bronchus and continues into the respiratory bronchioles. Bronchial glands are present in the propria submucosa and tela submucosa of the principal bronchi. The musculocartilaginous tunic is localized to the extrapulmonary portion of the principal bronchus. The bronchial cartilages are irregular shaped plates and limited to the extrapulmonary portion of the principal bronchus. The visceral pleura is a simple squamous mesothelium covering the outer surface of the lung. © 2011 Blackwell Verlag GmbH.

Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections

PubMed Central

Simeonov, Ivan; Gong, Xiaoyan; Kim, Oekyung; Poss, Mary; Chiaromonte, Francesca; Fricks, John

2010-01-01

The cell response to virus infection and virus perturbation of that response is dynamic and is reflected by changes in cell susceptibility to infection. In this study, we evaluated the response of human epithelial cells to sequential infections with human respiratory syncytial virus strains A2 and B to determine if a primary infection with one strain will impact the ability of cells to be infected with the second as a function of virus strain and time elapsed between the two exposures. Infected cells were visualized with fluorescent markers, and location of all cells in the tissue culture well were identified using imaging software. We employed tools from spatial statistics to investigate the likelihood of a cell being infected given its proximity to a cell infected with either the homologous or heterologous virus. We used point processes, K-functions, and simulation procedures designed to account for specific features of our data when assessing spatial associations. Our results suggest that intrinsic cell properties increase susceptibility of cells to infection, more so for RSV-B than for RSV-A. Further, we provide evidence that the primary infection can decrease susceptibility of cells to the heterologous challenge virus but only at the 16 h time point evaluated in this study. Our research effort highlights the merits of integrating empirical and statistical approaches to gain greater insight on in vitro dynamics of virus-host interactions. PMID:21994640

Maternal milk protects infants against bronchiolitis during the first year of life. Results from an Italian cohort of newborns.

PubMed

Lanari, Marcello; Prinelli, Federica; Adorni, Fulvio; Di Santo, Simona; Faldella, Giacomo; Silvestri, Michela; Musicco, Massimo

2013-06-01

Bronchiolitis is one of the primary causes of hospitalization in infancy. We evaluated the effect of breastfeeding on the occurrence of hospitalization for bronchiolitis in the first year of life. In a prospective cohort study, 1,814 newborns of =33 weeks of gestational age (wGA) were enrolled in 30 Italian Neonatology Units and followed-up for 1 year to assess hospitalizations for bronchiolitis. Children were grouped as 'never breastfed' and 'ever breastfed'; these latter were further divided into those 'exclusively breastfed' and 'breastfed associated with milk formula'. The risk of hospitalization for bronchiolitis was evaluated with survival analysis, and hazard ratios (HR) with 95% confidence interval [95% CI] were calculated. Among enrolled newborns 22.9% were 'never breastfed'; in the breastfed group, 65% were 'exclusively breastfed' and 35% were 'breastfed with associated milk formula'. At 12 months of age, the risk of hospitalization for bronchiolitis was significantly higher in the 'never breastfed' group (HR: 1.57; 95% CI: 1.00-2.48). 'Breastfed associated with formula milk' and 'exclusively breastfed' groups were at similar risk of hospitalization for bronchiolitis. This observed protective effect of maternal milk was not explained by the higher prevalence of conditions able to increase the risk of bronchiolitis among 'never breastfed newborns'. Breastfeeding, even in association with formula milk, reduces the risk of hospitalization for bronchiolitis during the first year of life. Encouraging breastfeeding might be an effective/inexpensive measure of prevention of lower respiratory tract infections in infancy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.

PubMed

Carbonell-Estrany, Xavier; Simões, Eric A F; Dagan, Ron; Hall, Caroline B; Harris, Brian; Hultquist, Micki; Connor, Edward M; Losonsky, Genevieve A

2010-01-01

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. This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

PubMed

de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

2016-11-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Development of Electrochemiluminescent Serology Assays to Measure the Humoral Response to Antigens of Respiratory Syncytial Virus.

PubMed

Maifeld, Sarah V; Ro, Bodrey; Mok, Hoyin; Chu, Marla; Yu, Li; Yamagata, Ryan; Leonardson, Tansy; Chio, Vera; Parhy, Bandita; Park, Samuel; Carlson, Marcia; Machhi, Shushil; Ulbrandt, Nancy; Falsey, Ann R; Walsh, Edward E; Wang, C Kathy; Esser, Mark T; Zuo, Fengrong

2016-01-01

Sensitive and precise serology assays are needed to measure the humoral response to antigens of respiratory syncytial virus (RSV) following natural infection or vaccination. We developed and evaluated a collection of electrochemiluminescent (ECL) serology assays using four RSV antigens (F, N, Ga and Gb). To assess the merits of ECL technology, the four ECL serology assays were evaluated using a well-characterized "gold standard" panel of acute and convalescent serum samples from fifty-nine RSV-positive and thirty RSV-negative elderly subjects (≥65 years old). The combined results from the four ECL assays demonstrated good concordance to the "gold standard" diagnosis, reaching 95% diagnostic sensitivity and 100% diagnostic specificity. Additionally, a combination of ECL assays provided higher diagnostic sensitivity than a commercially available diagnostic ELISA or cell-based microneutralization assay. In summary, these data demonstrate the advantages of using ECL-based serology assays and highlight their use as a sensitive diagnostic approach to detect recent RSV infection in an elderly population.

Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein.

PubMed

Tian, Daiyin; Battles, Michael B; Moin, Syed M; Chen, Man; Modjarrad, Kayvon; Kumar, Azad; Kanekiyo, Masaru; Graepel, Kevin W; Taher, Noor M; Hotard, Anne L; Moore, Martin L; Zhao, Min; Zheng, Zi-Zheng; Xia, Ning-Shao; McLellan, Jason S; Graham, Barney S

2017-11-30

A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.

Resistance to Human Respiratory Syncytial Virus (RSV) Infection Induced by Immunization of Cotton Rats with a Recombinant Vaccinia Virus Expressing the RSV G Glycoprotein

NASA Astrophysics Data System (ADS)

Elango, Narayanasamy; Prince, Gregory A.; Murphy, Brian R.; Venkatesan, Sundararajan; Chanock, Robert M.; Moss, Bernard

1986-03-01

A cDNA copy of the G glycoprotein gene of human respiratory syncytial virus (RSV) was placed under control of a vaccinia virus promoter and inserted into the thymidine kinase locus of the vaccinia virus genome. The recombinant vaccinia virus retained infectivity and expressed a 93-kDa protein that migrated with the authentic RSV G glycoprotein upon polyacrylamide gel electrophoresis. Glycosylation of the expressed protein and transport to the cell surface were demonstrated in the absence of other RSV proteins. Cotton rats that were inoculated intradermally with the infectious recombinant virus produced serum antibody to the G glycoprotein that neutralized RSV in vitro. Furthermore, the vaccinated animals were resistant to lower respiratory tract infection upon intranasal inoculation with RSV and had reduced titers of RSV in the nose.

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

PubMed Central

Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya

2016-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4+ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and

Cystic Fibrosis Pulmonary Exacerbations Attributable to Respiratory Syncytial Virus and Influenza: A Population-Based Study.

PubMed

Somayaji, Ranjani; Goss, Christopher H; Khan, Umer; Neradilek, Moni; Neuzil, Kathleen M; Ortiz, Justin R

2017-06-15

Characterization of the role of respiratory viral pathogens on cystic fibrosis (CF) pulmonary disease is needed. We aimed to determine the association of influenza and respiratory syncytial virus (RSV) activity with risk of pulmonary exacerbation (PEx) in persons with CF in the United States. We conducted a cohort study from January 2003 to March 2009 using the CF Foundation Patient Registry merged with Centers for Disease Control and Prevention respiratory virus surveillance data. The primary goal was to determine the association between regional influenza or RSV detections with risk of PEx requiring intravenous antibiotics or hospitalization. We analyzed outcomes by geographic region and week of event using multivariable regression models adjusted for demographic and clinical predictors of PEx stratified for children (<18 years) and adults (≥18 years) to calculate relative risks (RRs) of PEx. There were 21022 individuals (52% male) in the CF patient cohort in 2003 comprised of 12702 children and 8320 adults. The overall incidence rate of PEx was 521.9 per 10000 person-months. In children, a 10% increase in the proportion of surveillance tests positive for influenza or RSV was significantly associated with increased PEx risk (RR, 1.02; 95% confidence interval [CI], 1.01-1.03) and (RR, 1.05; 95% CI, 1.02-1.07), respectively. In adults, surveillance tests positive for influenza (RR, 1.02; 95% CI, 1.01-1.02), but not RSV (RR, 0.99; 95% CI, .98-1.01), had a significant association with PEx risk. Our large CF population-based cohort demonstrated a significant association between PEx risk and influenza activity in children and adults and with RSV activity in children. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Respiratory syncytial virus prophylaxis in cystic fibrosis: the Canadian registry of palivizumab data (2005-2016).

PubMed

Mitchell, Ian; Wong, S K; Paes, B; Ruff, M; Bjornson, C; Li, A; Lanctôt, K L

2018-05-04

Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24 months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5-8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6-9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.

Using high-flow nasal cannulas for infants with bronchiolitis admitted to paediatric wards is safe and feasible.

PubMed

Heikkilä, Paula; Sokuri, Paula; Mecklin, Minna; Nuolivirta, Kirsi; Tapiainen, Terhi; Peltoniemi, Outi; Renko, Marjo; Korppi, Matti

2018-05-26

Using a high-flow nasal cannula (HFNC) for infant bronchiolitis is increasingly common, but insufficiently studied. In this retrospective study, we examined the outcomes of HFNC and compared infants who did and did not respond to this oxygen delivery method. This 2012-2015 study of six Finnish hospitals focused on 88 infants under 12 months who received HFNC: 53 on paediatric wards and 35 in paediatric intensive care units (PICUs). We reviewed patient files for underlying factors, clinical parameters and HFNC treatment. The treatment failed if the patient was transferred to another respiratory support. We found HFNC treatment was successful in 76 (86%) infants, including all 53 on the paediatric wards and 23/35 PICU patients. The responders' heart rates were significantly lower, and their oxygen saturation was significantly higher at 60 minutes after HFNC treatment started and then stayed relatively constant. Their respiratory rate was only significantly lower after 360 minutes. In non-responders, the respiratory rate initially decreased but was higher at 180 and 360 minutes after the start of HFNC. We found preliminary evidence that oxygen support needs and heart rate were useful early predictors of HFNC therapy success in infants hospitalised with bronchiolitis, but respiratory rate was not. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

2005-01-20

Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

Nasogastric Hydration in Infants with Bronchiolitis Less Than 2 Months of Age.

PubMed

Oakley, Ed; Bata, Sonny; Rengasamy, Sharmila; Krieser, David; Cheek, John; Jachno, Kim; Babl, Franz E

2016-11-01

To determine whether nasogastric hydration can be used in infants less than 2 months of age with bronchiolitis, and characterize the adverse events profile of these infants compared with infants given intravenous (IV) fluid hydration. A descriptive retrospective cohort study of children with bronchiolitis under 2 months of age admitted for hydration at 3 centers over 3 bronchiolitis seasons was done. We determined type of hydration (nasogastric vs IV fluid hydration) and adverse events, intensive care unit admission, and respiratory support. Of 491 infants under 2 months of age admitted with bronchiolitis, 211 (43%) received nonoral hydration: 146 (69%) via nasogastric hydration and 65 (31%) via IV fluid hydration. Adverse events occurred in 27.4% (nasogastric hydration) and 23.1% (IV fluid hydration), difference of 4.3%; 95%CI (-8.2 to 16.9), P = .51. The majority of adverse events were desaturations (21.9% nasogastric hydration vs 21.5% IV fluid hydration, difference 0.4%; [-11.7 to 12.4], P = .95). There were no pulmonary aspirations in either group. Apneas and bradycardias were similar in each group. IV fluid hydration use was positively associated with intensive care unit admission (38.5% IV fluid hydration vs 19.9% nasogastric hydration; difference 18.6%, [5.1-32.1], P = .004); and use of ventilation support (27.7% IV fluid hydration vs 15.1% nasogastric hydration; difference 12.6 [0.3-23], P = .03). Fewer infants changed from nasogastric hydration to IV fluid hydration than from IV fluid hydration to nasogastric hydration (12.3% vs 47.7%; difference -35.4% [-49 to -22], P < .001). Nasogastric hydration can be used in the majority of young infants admitted with bronchiolitis. Nasogastric hydration and IV fluid hydration had similar rates of complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

PubMed

Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

2015-12-01

Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

Central Role of the NF-κB Pathway in the Scgb1a1-Expressing Epithelium in Mediating Respiratory Syncytial Virus-Induced Airway Inflammation.

PubMed

Tian, Bing; Yang, Jun; Zhao, Yingxin; Ivanciuc, Teodora; Sun, Hong; Wakamiya, Maki; Garofalo, Roberto P; Brasier, Allan R

2018-06-01

Lower respiratory tract infection with respiratory syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role of adaptive immunity in RSV infection, the identity of the major sentinel cells initially triggering inflammation is controversial. Here we evaluate the role of nonciliated secretoglobin ( Scgb1a1 )-expressing bronchiolar epithelial cells in RSV infection. Mice expressing a tamoxifen (TMX)-inducible Cre recombinase-estrogen receptor fusion protein (CreERTM) knocked into the Scgb1a1 locus were crossed with mice that harbor a RelA conditional allele ( RelA fl ), with loxP sites flanking exons 5 to 8 of the Rel homology domain. The Scgb1a1 CreERTM/+ × RelA fl/fl mouse is a RelA conditional knockout (RelA CKO ) of a nonciliated epithelial cell population enriched in the small bronchioles. TMX-treated RelA CKO mice have reduced pulmonary neutrophilic infiltration and impaired expression and secretion of NF-κB-dependent cytokines in response to RSV. In addition, RelA CKO mice had reduced expression levels of interferon (IFN) regulatory factor 1/7 (IRF1/7) and retinoic acid-inducible gene I (RIG-I), components of the mucosal IFN positive-feedback loop. We demonstrate that RSV replication induces RelA to complex with bromodomain-containing protein 4 (BRD4), a cofactor required for RNA polymerase II (Pol II) phosphorylation, activating the atypical histone acetyltransferase (HAT) activity of BRD4 required for phospho-Ser2 Pol II formation, histone H3K122 acetylation, and cytokine secretion in vitro and in vivo TMX-treated RelA CKO mice have less weight loss and reduced airway obstruction/hyperreactivity yet similar levels of IFN-γ production despite higher levels of virus production. These data indicate that the nonciliated Scgb1a1 -expressing epithelium is a major innate sensor for restricting RSV infection by mediating neutrophilic inflammation and chemokine and mucosal IFN production via the RelA-BRD4 pathway. IMPORTANCE RSV

New Generation Live Vaccines against Human Respiratory Syncytial Virus Designed by Reverse Genetics

PubMed Central

Collins, Peter L.; Murphy, Brian R.

2005-01-01

Development of a live pediatric vaccine against human respiratory syncytial virus (RSV) is complicated by the need to immunize young infants and the difficulty in balancing attenuation and immunogenicity. The ability to introduce desired mutations into infectious virus by reverse genetics provides a method for identifying and designing highly defined attenuating mutations. These can be introduced in combinations as desired to achieve gradations of attenuation. Attenuation is based on several strategies: multiple independent temperature-sensitive point mutations in the polymerase, a temperature-sensitive point mutation in a transcription signal, a set of non–temperature-sensitive mutations involving several genes, deletion of a viral RNA synthesis regulatory protein, and deletion of viral IFN α/β antagonists. The genetic stability of the live vaccine can be increased by judicious choice of mutations. The virus also can be engineered to increase the level of expression of the protective antigens. Protective antigens from antigenically distinct RSV strains can be added or swapped to increase the breadth of coverage. Alternatively, the major RSV protective antigens can be expressed from transcription units added to an attenuated parainfluenza vaccine virus, making a bivalent vaccine. This would obviate the difficulties inherent in the fragility and inefficient in vitro growth of RSV, simplifying vaccine design and use. PMID:16113487

A comparison of human metapneumovirus and respiratory syncytial virus WHO-defined severe pneumonia in Moroccan children.

PubMed

Jroundi, I; Mahraoui, C; Benmessaoud, R; Moraleda, C; Tligui, H; Seffar, M; El Kettani, S E C; Benjelloun, B S; Chaacho, S; Muñoz-Almagro, C; Ruiz, J; Alonso, P L; Bassat, Q

2016-02-01

Acute respiratory infections remain the principal cause of morbidity and mortality in Moroccan children. Besides bacterial infections, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are prominent among other viruses due to their high prevalence and association with severe clinical episodes. We aimed to describe and compare RSV- and hMPV-associated cases of WHO-defined severe pneumonia in a paediatric population admitted to Morocco's reference hospital. Children aged 2-59 months admitted to the Hôpital d'Enfants de Rabat, Morocco meeting WHO-defined severe pneumonia criteria were recruited during 14 months and thoroughly investigated to ascertain a definitive diagnosis. Viral prevalence of RSV, hMPV and other viruses causing respiratory symptoms was investigated in nasopharyngeal aspirate samples through the use of molecular methods. Of the 683 children recruited and included in the final analysis, 61/683 (8·9%) and 124/683 (18·2%) were infected with hMPV and RSV, respectively. Besides a borderline significant tendency for higher age in hMPV cases, patients infected with either of the viruses behaved similarly in terms of demographics, patient history, past morbidity and comorbidity, vaccination history, socioeconomic background and family environment. Clinical presentation on arrival was also similar for both viruses, but hMPV cases were associated with more severity than RSV cases, had a higher risk of intensive care need, and received antibiotic treatment more frequently. RSV and hMPV are common and potentially life-threatening causes of WHO-defined pneumonia in Moroccan children. Both viruses show indistinctive clinical symptomatology, but in Moroccan children, hMPV was associated with a more severe evolution.

Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells: Effectiveness of N-Acetylcysteine

PubMed Central

Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A.; Cortijo, Julio

2012-01-01

Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H2O2 levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD. PMID:23118923

Epidemiology, clinical characteristics, laboratory findings and severity of respiratory syncytial virus acute lower respiratory infection in Malaysian children, 2008-2013.

PubMed

Ng, Khuen F; Tan, Kah K; Sam, Zhi H; Ting, Grace Ss; Gan, Wan Y

2017-04-01

The aim of this study is to describe epidemiology, clinical features, laboratory data and severity of respiratory syncytial virus (RSV) acute lower respiratory infection (ALRI) in Malaysian children and to determine risk factors associated with prolonged hospital stay, paediatric intensive care unit (PICU) admission and mortality. Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 450 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2008 to 2013 with documented diagnosis of RSV ALRI were collected and analysed. Most admissions were children below 2 years old (85.8%; 386/450). Commonest symptoms were fever (84.2%; 379/450), cough (97.8%; 440/450) and rhinorrhea (83.6%; 376/450). The median age among febrile patients (n = 379) was 9.0 months with interquartile range (IQR) of 4.0-19.0 months whereas the median age among those who were apyrexial (n = 71) was 2 months with IQR of 1-6 months (P-value <0.001). 15.3% (69/450) needed intensive care and 1.6% (7/450) died. Young age, history of prematurity, chronic comorbidity and thrombocytosis were significantly associated with prolonged hospital stay, PICU admission and mortality. Infants less than 6 months old with RSV ALRI tend to be afebrile at presentation. Younger age, history of prematurity, chronic comorbidity and thrombocytosis are predictors of severe RSV ALRI among Malaysian children. Case fatality rate for Malaysian children below 5 years of age with RSV ALRI in our centre is higher than what is seen in developed countries, suggesting that there is room for improvement. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

PubMed

Jat, Kana R; Mathew, Joseph L

2015-01-07

Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in infants. There is no specific treatment for bronchiolitis except for supportive therapy. Continuous positive airway pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing deflation of over-distended lungs in bronchiolitis. The increase in airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. In observational studies, CPAP is found to be beneficial in acute bronchiolitis. To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. We searched CENTRAL (2014, Issue 3), MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981 to April 2014) and LILACS (1982 to April 2014). We considered randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. Two review authors independently assessed study eligibility, extracted data using a structured proforma, analysed the data and performed meta-analyses. We included two studies with a total of 50 participants under 12 months of age. In one study there was a high risk of bias for incomplete outcome data and selective reporting, and both studies had an unclear risk of bias for several domains including random sequence generation. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (two RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality evidence). Neither trial measured our other primary outcome of time to recovery. One trial found that CPAP significantly improved respiratory rate compared with no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute, 95% CI -9.30 to -2.10), although the other

Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

PubMed Central

Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

2018-01-01

Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

PubMed

Botosso, Viviane F; Zanotto, Paolo M de A; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E; Vieira, Sandra E; Stewien, Klaus E; Peret, Teresa C T; Jamal, Leda F; Pardini, Maria I de M C; Pinho, João R R; Massad, Eduardo; Sant'anna, Osvaldo A; Holmes, Eddie C; Durigon, Edison L

2009-01-01

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

PubMed Central

Botosso, Viviane F.; Zanotto, Paolo M. de A.; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E.; Vieira, Sandra E.; Stewien, Klaus E.; Peret, Teresa C. T.; Jamal, Leda F.; Pardini, Maria I. de M. C.; Pinho, João R. R.; Massad, Eduardo; Sant'Anna, Osvaldo A.; Holmes, Eddie C.; Durigon, Edison L.

2009-01-01

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites. PMID:19119418

Helmet Versus Nasal-Prong CPAP in Infants With Acute Bronchiolitis.

PubMed

Mayordomo-Colunga, Juan; Rey, Corsino; Medina, Alberto; Martínez-Camblor, Pablo; Vivanco-Allende, Ana; Concha, Andrés

2018-04-01

Nasal prongs are frequently used to deliver noninvasive CPAP in bronchiolitis, especially in the youngest children. A helmet interface is an alternative that might be comparable to nasal prongs. We sought to compare these interfaces. We performed a prospective, randomized, crossover, single-center study in an 8-bed multidisciplinary pediatric ICU in a university hospital. Infants age <3 months who were consecutively admitted to the pediatric ICU during a bronchiolitis epidemic season and fulfilled inclusion criteria were recruited. Subjects were randomly allocated to receive CPAP via a helmet or nasal prongs for 60 min. The subjects were then placed on the other CPAP system for another 60-min period (helmet then nasal prongs [H-NP] or nasal prongs then helmet [NP-H]). Measurements were taken at 30, 60, 90, and 120 min. Failure was defined as the need for further respiratory support. Sixteen subjects were included, with 9 in the H-NP group and 7 in the NP-H group. CPAP significantly reduced respiratory distress, showing no differences between the H-NP and NP-H groups in terms of improving the Modified Wood's Clinical Asthma Score from 4.8 ± 1 to 3 ± 0.9 and 2.7 ± 1.7 points at 60 min and 120 min in the H-NP group, respectively, and from 4.2 ± 0.9 to 2.8 ± 0.9 and to 2.9 ± 0.9 at 60 min and 120 min, respectively, in the NP-H group. Sedatives were used in only 3 subjects (2 in the NP-H group, P = .77). The failure rate was similar in both groups (3 of 9 subjects vs 3 of 7 subjects, P = .70). No significant differences were seen for heart rate, breathing frequency, F IO 2 , or transcutaneous oxygen saturation response. Our results suggest that CPAP delivered by nasal prongs and CPAP delivered by helmet are similar in terms of efficacy in young infants with acute bronchiolitis. Copyright © 2018 by Daedalus Enterprises.

Association between Hyponatremia and Higher Bronchiolitis Severity among Children in the Intensive Care Unit with Bronchiolitis

PubMed Central

Hasegawa, Kohei; Stevenson, Michelle D.; Mansbach, Jonathan M.; Schroeder, Alan R.; Sullivan, Ashley F.; Espinola, Janice A.; Piedra, Pedro A.; Camargo, Carlos A.

2016-01-01

Background It remains unclear whether hyponatremia independently predicts a higher severity in children with bronchiolitis. Objective To investigate the association between hyponatremia and bronchiolitis severity in children hospitalized to the intensive care unit (ICU) for bronchiolitis. Methods We conducted a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis during the winters of 2007 to 2010. We classified patients into two groups: normonatremia (135–145 mEq/L) and hyponatremia (<135 mEq/L) based on the first-measured serum sodium concentration on the day of hospitalization. Outcomes were use of mechanical ventilation and ICU length-of-stay (LOS). To examine the association of sodium status with outcomes, we fit logistic and linear regression models with propensity score adjustment. Results Of 231 children hospitalized to the ICU for bronchiolitis, 193 patients (84%) were categorized into the normonatremia group, and 38 children (16%) into hyponatremia group. Compared to children with normonatremia, those with hyponatremia had higher risks of mechanical ventilation use (40% vs. 58%; P=0.04) and longer ICU LOS (median, 3 days vs. 6 days; P=0.007). Likewise, in the adjusted analyses, children with hyponatremia had significantly higher risks of mechanical ventilation use (OR, 2.14; 95%CI, 1.03–4.48; P=0.04) and longer ICU LOS (β-coefficient 2.21 days; 95%CI, 0.68–3.73 days; P=0.003). Conclusions In this prospective, multicenter study of children hospitalized for bronchiolitis, hyponatremia on the day of hospitalization was associated with a higher severity. Our data support hyponatremia as a prognostic factor that might improve the ability of clinicians to predict the disease course of children with severe bronchiolitis. PMID:26136313

Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Morrow, Matthew P; Kraynyak, Kimberly A; McCoy, Jay R; Yim, Kevin C; Muthumani, Karuppiah; Humeau, Laurent; Weiner, David B; Sardesai, Niranjan Y; Broderick, Kate E

2017-05-15

Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy. Copyright © 2017. Published by Elsevier Ltd.

Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Gaie; Jeffree, Chris E.; McDonald, Terence

2004-10-01

The assembly of respiratory syncytial virus (RSV) in lipid-rafts was examined in Hep2 cells. Confocal and electron microscopy showed that during RSV assembly, the cellular distribution of the complement regulatory proteins, decay accelerating factor (CD55) and CD59, changes and high levels of these cellular proteins are incorporated into mature virus filaments. The detergent-solubility properties of CD55, CD59, and the RSV fusion (F) protein were found to be consistent with each protein being located predominantly within lipid-raft structures. The levels of these proteins in cell-released virus were examined by immunoelectronmicroscopy and found to account for between 5% and 15% of themore » virus attachment (G) glycoprotein levels. Collectively, our findings suggest that an intimate association exists between RSV and lipid-raft membranes and that significant levels of these host-derived raft proteins, such as those regulating complement activation, are subsequently incorporated into the envelope of mature virus particles.« less

Rapid testing for respiratory syncytial virus in a paediatric emergency department: benefits for infection control and bed management.

PubMed

Mills, J M; Harper, J; Broomfield, D; Templeton, K E

2011-03-01

Respiratory syncytial virus (RSV) is responsible for annual winter outbreaks of respiratory tract infection among children in temperate climates, placing severe pressure on hospital beds. Cohorting of affected infants has been demonstrated to be an effective strategy in reducing nosocomial transmission of RSV, and may keep cubicles free for other patients who require them. Testing of symptomatic children for RSV is standard practice, but unfortunately traditional laboratory testing is not rapid enough to aid decision-making processes. Rapid point-of-care testing (POCT) in the emergency department has been suggested as an alternative. We performed a prospective study to quantify the amount of cubicle time saved by using POCT results to allow a targeted cohorting strategy. Over the four-month study period, the POCT allowed 183 children to be admitted directly to a designated cohort area, thus saving 568.5 cubicle-days for other patients. This is equivalent to five cubicles being left free for each day of the study period. This is the first time the benefits of using POCT have been quantified in this way. POCT for RSV is a safe, cost-effective and efficient way to improve bed management. Copyright © 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Secondary RNA structure and its role in RNA interference to silence the respiratory syncytial virus fusion protein gene.

PubMed

Vig, Komal; Lewis, Nuruddeen; Moore, Eddie G; Pillai, Shreekumar; Dennis, Vida A; Singh, Shree R

2009-11-01

RNA interference (RNAi) is a post-transcriptional, gene silencing mechanism which uses small interfering RNA molecules (siRNA) for gene silencing. Respiratory Syncytial Virus (RSV) is an important respiratory pathogen of medical significance that causes high mortality in infants. The fusion (F) protein of RSV is a good target for therapeutic purposes as it is primarily responsible for penetration of the virus into host cells and subsequent syncytium formation during infection. In the present study, four siRNAs were designed and used individually as well as a mixture, to silence the RSV F gene. The relationship between siRNA design, target RNA structure, and their thermodynamics was also investigated. Silencing of F gene was observed using indirect immunofluorescence, western blot, reverse transcription PCR, and progeny viral titers. Our results show F gene silencing by all the four siRNAs individually and collectively. RT-PCR analysis revealed a decrease in mRNA level which corresponded to decreased F protein expression. siRNAs also inhibited RSV progeny as shown by viral titer estimation on infected HEp-2 cells. The present study demonstrates the silencing of the F gene using siRNA. Thermodynamic characteristics of the target RSV mRNA and siRNA seem to play an important role in siRNA gene silencing efficiency.

Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study.

PubMed

García-García, María Luz; Calvo, Cristina; Rey, Cristina; Díaz, Beatriz; Molinero, Maria Del Mar; Pozo, Francisco; Casas, Inmaculada

2017-01-01

Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children's mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.

A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS).

PubMed

Paes, B; Mitchell, I; Li, A; Lanctôt, K L

2012-10-01

We examined the dosing regimens, compliance, and outcomes of premature infants who received palivizumab within the Canadian Registry of Palivizumab (CARESS). Infants receiving ≥1 dose of palivizumab during the 2006-2011 respiratory syncytial virus (RSV) seasons were recruited across 30 sites. Respiratory illness events were captured monthly. Infants ≤32 completed weeks gestational age (GA) (Group 1) were compared to 33-35 completed weeks GA infants (Group 2) following prophylaxis. In total, 6,654 patients were analyzed (Group 1, n = 5,183; Group 2, n = 1,471). The mean GA was 29.9 ± 2.9 versus 34.2 ± 2.2 weeks for Groups 1 and 2, respectively. Group differences were significant (all p-values <0.05) for the following: proportion of males, Caucasians, siblings, multiple births, maternal smoking, smoking during pregnancy, household smokers, >5 household individuals, birth weight, and enrolment age. Overall, infants received 92.6 % of expected injections. Group 1 received significantly more injections, but a greater proportion of Group 2 received injections within recommended intervals. The hospitalization rates were similar for Groups 1 and 2 for respiratory illness (4.7 % vs. 3.7 %, p = 0.1) and RSV (1.5 % vs. 1.4 %, p = 0.3). Neither the time to first respiratory illness [hazard ratio = 0.9, 95 % confidence interval (CI) 0.7-1.2, p = 0.5] nor to first RSV hospitalization (hazard ratio = 1.3, 95 % CI 0.8-2.2, p = 0.3) were different. Compliance with RSV prophylaxis is high. Despite the higher number of palivizumab doses in infants ≤32 completed weeks GA, the two groups' respiratory illness and RSV-positive hospitalization rates were similar.

Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread

PubMed Central

McCarty, Thomas; Martin, Scott E.; Le Nouën, Cyril; Buehler, Eugen; Chen, Yu-Chi; Smelkinson, Margery; Ganesan, Sundar; Fischer, Elizabeth R.; Brock, Linda G.; Liang, Bo; Munir, Shirin; Collins, Peter L.; Buchholz, Ursula J.

2016-01-01

Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells. Consistent with reduced spread, there was a 10-fold reduction in the release of infectious progeny virions in ARP2-depleted cells at 72 hr post-infection. In addition, we found that RSV infection induced filopodia formation and increased cell motility in A549 cells and that this phenotype was ARP2 dependent. Filopodia appeared to shuttle RSV to nearby uninfected cells, facilitating virus spread. Expression of the RSV F protein alone from a plasmid or heterologous viral vector in A549 cells induced filopodia, indicating a new role for the RSV F protein, driving filopodia induction and virus spread. Thus, this study identified roles for ARP2 and filopodia in RSV-induced cell motility, RSV production, and RSV cell-to-cell spread. PMID:27926942

Oxidative and antioxidative status of children with acute bronchiolitis.

PubMed

Dundaroz, Rusen; Erenberk, Ufuk; Turel, Ozden; Demir, Aysegul Dogan; Ozkaya, Emin; Erel, Ozcan

2013-01-01

Oxidative stress has been shown to contribute to the pathogenesis of acute and chronic lung inflammatory diseases. This article aimed to evaluate the oxidant/antioxidant status of children with acute bronchiolitis through the measurement of plasma total antioxidant capacity, total oxidant status, and oxidative stress index. Children with acute bronchiolitis admitted to the pediatric emergency department of a university hospital between January and April of 2012 were compared with age-matched healthy controls. Patients with acute bronchiolitis were classified as mild and moderate bronchiolitis. Oxidative and antioxidative status were assessed by measurement of plasma total antioxidant capacity, total oxidant status, and oxidative stress index. Thirty-one children with acute bronchiolitis aged between 3 months and 2 years, and 39 healthy children were included. Total oxidative status (TOS) was higher in patients with acute bronchiolitis than the control group (5.16±1.99 μmol H2O2 versus 3.78±1.78 μmol H2O2 [p=0.004]). Total antioxidant capacity (TAC) was lower in children with bronchiolitis than the control group (2.51±0.37 μmol Trolox eqv/L versus 2.75±0.39 μmol Trolox eqv/L [p=0.013]). Patients with moderate bronchiolitis presented higher TOS levels than those with mild bronchiolitis and the control group (p=0.03, p<0.001, respectively). Patients with moderate bronchiolitis had higher oxidative stress index levels than the control group (p=0.015). Oxygen saturation level of bronchiolitis patients was inversely correlated with TOS (r=-0.476, p<0.05). The balance between oxidant and antioxidant systems is disrupted in children with moderate bronchiolitis, which indicates that this stress factor may have a role in the pathogenesis of the disease. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Recombinant Influenza Virus Carrying the Conserved Domain of Respiratory Syncytial Virus (RSV) G Protein Confers Protection against RSV without inflammatory disease

PubMed Central

Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul; Lee, Young-Tae; Cho, Min-Kyoung; Kwon, Young-Man; Lee, Jong Seok; Plemper, Richard K.; Kang, Sang-Moo

2014-01-01

Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses (PR8/RSV.HA-G) carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein. PR8/RSV.HA-G virus showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice with PR8/RSV.HA-G induced IgG2a isotype dominant antibodies and RSV neutralizing activity. Mice with single intranasal inoculation of PR8/RSV.HA-G were protected against RSV infection as evidenced by significant reduction of lung viral loads to a detection limit upon RSV challenge. PR8/RSV.HA-G inoculation of mice did not induce pulmonary eosinophilia and inflammation upon RSV infection. These findings support a concept that recombinant influenza viruses carrying the RSV G conserved-domain can be developed as a promising RSV vaccine candidate without pulmonary disease. PMID:25553517

Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palomo, Concepción; Mas, Vicente; Vázquez, Mónica

Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to exploremore » the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.« less

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.

PubMed

Iwane, Marika K; Chaves, Sandra S; Szilagyi, Peter G; Edwards, Kathryn M; Hall, Caroline B; Staat, Mary A; Brown, Cedric J; Griffin, Marie R; Weinberg, Geoffrey A; Poehling, Katherine A; Prill, Mila M; Williams, John V; Bridges, Carolyn B

2013-04-01

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.

Respiratory syncytial virus infection and disease in infants and young children observed from birth in Kilifi District, Kenya.

PubMed

Nokes, D James; Okiro, Emelda A; Ngama, Mwanajuma; Ochola, Rachel; White, Lisa J; Scott, Paul D; English, Michael; Cane, Patricia A; Medley, Graham F

2008-01-01

In developing countries, there are few data that characterize the disease burden attributable to respiratory syncytial virus (RSV) and clearly define which age group to target for vaccine intervention. Six hundred thirty-five children, recruited during the period 2002-2003, were intensively monitored until each experienced 3 epidemics of RSV infection. RSV infection was diagnosed using immunofluorescence of nasal washing specimens collected at each episode of acute respiratory infection. Incidence estimates were adjusted for seasonality of RSV exposure. For 1187 child-years of observation (CYO), a total of 409 (365 primary and 82 repeat) episodes of RSV infection were identified. Adjusted incidence estimates of lower respiratory tract infection (LRTI), severe LRTI, and hospital admission were 90 cases per 1000 CYO, 43 cases per 1000 CYO, and 10 cases per 1000 CYO, respectively, and corresponding estimates among infants were 104 cases per 1000 CYO, 66 cases per 1000 CYO, and 13 cases per 1000 CYO, respectively. The proportion of cases of all-cause LRTI, and severe LRTI and hospitalizations attributable to RSV in the cohort was 13%, 19%, and 5%, respectively. Fifty-five percent to 65% of RSV-associated LRTI and severe LRTI occurred in children aged >6 months. The risk of RSV disease following primary symptomatic infection remained significant beyond the first year of life, and one-quarter of all reinfections were associated with LRTI. RSV accounts for a substantial proportion of the total respiratory disease in this rural population; we estimate that 85,000 cases of severe LRTI per year occur in infants in Kenya. The majority of this morbidity occurs during late infancy and early childhood--ages at which the risk of disease following infection remains significant. Disease resulting from reinfection is common. Our results inform the debate on the target age group and effectiveness of a vaccine.

Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya

2015-08-15

The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH proteinmore » in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.« less

Genetic variability human respiratory syncytial virus subgroups A and B in Turkey during six successive epidemic seasons, 2009-2015.

PubMed

Bayrakdar, Fatma; Kocabas, Can Naci; Altas, Ayse Basak; Kavuncuoglu, H Gokhan; Cosgun, Yasemin; Mısırlıoglu, Emine Dibek; Durmaz, Ihsan; Korukluoglu, Gulay; Ozkul, Aykut

2018-03-01

Human respiratory syncytial virus (HRSV) is most important viral respiratory pathogen of acute lower respiratory tract infections in infants and young children worldwide. The circulating pattern and genetic characteristics in the HRSV attachment glycoprotein gene were investigated in Turkey during six consecutive seasons from 2009 to 2015. HRSVA was dominant in the all epidemic seasons except 2011-2012 season. Partial sequences of the HVR2 region of the G gene of 479 HRSVA and 135 HRSVB were obtained. Most Turkish strains belonged to NA1, ON1, and BA9, which were the predominant genotypes circulating worldwide. Although three novel genotypes, TR-A, TR-BA1, and TR-BA2, were identified, they were not predominant. Clinical data were available for 69 HRSV-positive patients who were monitored due to acute lower respiratory tract illness. There were no significant differences in the clinical diagnosis, hospitalization rates, laboratory findings and treatment observed between the HRSVA and HRSVB groups, and co-infections in this study. The major population afflicted by HRSV infections included infants and children between 13 and 24 months of age. We detected that the CB1, GB5, and THB strains clustered in the same branch with a bootstrap value of 100%. CB-B and BA12 strains clustered in the same branch with a bootstrap value of 65%. The BA11 genotype was clustered in the BA9 genotype in our study. The present study may contribute on the molecular epidemiology of HRSV in Turkey and provide data for HRSV strains circulating in local communities and other regions worldwide. © 2017 Wiley Periodicals, Inc.

Profilin Is Required for Optimal Actin-Dependent Transcription of Respiratory Syncytial Virus Genome RNA

PubMed Central

Burke, Emily; Mahoney, Nicole M.; Almo, Steven C.; Barik, Sailen

2000-01-01

Transcription of human respiratory syncytial virus (RSV) genome RNA exhibited an obligatory need for the host cytoskeletal protein actin. Optimal transcription, however, required the participation of another cellular protein that was characterized as profilin by a number of criteria. The amino acid sequence of the protein, purified on the basis of its transcription-optimizing activity in vitro, exactly matched that of profilin. RSV transcription was inhibited 60 to 80% by antiprofilin antibody or poly-l-proline, molecules that specifically bind profilin. Native profilin, purified from extracts of lung epithelial cells by affinity binding to a poly-l-proline matrix, stimulated the actin-saturated RSV transcription by 2.5- to 3-fold. Recombinant profilin, expressed in bacteria, stimulated viral transcription as effectively as the native protein and was also inhibited by poly-l-proline. Profilin alone, in the absence of actin, did not activate viral transcription. It is estimated that at optimal levels of transcription, every molecule of viral genomic RNA associates with approximately the following number of protein molecules: 30 molecules of L, 120 molecules of phosphoprotein P, and 60 molecules each of actin and profilin. Together, these results demonstrated for the first time a cardinal role for profilin, an actin-modulatory protein, in the transcription of a paramyxovirus RNA genome. PMID:10623728

[Quantitative fluorogenic real-time PCR assay for respiratory syncytial virus detection].

PubMed

Zhang, Qi-wei; You, Shang-you; Sun, Ji-min; Wu, Qi; Yu, Chun-hua; Zhang, Chu-yu

2005-07-01

To Establish a rapid and objective quantitative fluorogenic real-time PCR assay for early detection of human respiratory syncytial virus (hRSV). Two pairs of primers and one TaqMan Fluorogenic probe that are specific for the recognition of the most conservative N gene of hRSV for virus detection with LighCycler PCR in 93 nasopharyngeal secretion specimens collected from infants and young children. The assay was compared with virus isolation, routine PCR, nested PCR, and enzyme-linked immunosorbent assay (ELISA). This TaqMan assay had a sensitivity of 1 x 10(2) cDNA copies/microl with a dynamic range between 1 x 10(2) and 1 x 10(7) cDNA copies/microl, which was the same as that of nested PCR, but 10 times more sensitive than routine PCR. The specificity of the assay was evaluated by comparing hRSV with polivirus type 1, coxsackie virus type 2, influenza A, influenza B and adenovirus type 7. A PCR product of the expected size (195 bp) was produced and fluorescence signal detected for hRSV, but not for any of the other viruses. The results in LightCycler and Rotor-Gene instrument were consistent. Forty-four specimens (43.9%) were hRSV-positive with this assay and 4 (4/93,4.3%) were hRSV-positive with ELISA, showing rather low correlation between the two methods. No visible relation was found between the concentration of hRSV RNA and severity of the disease. This assay is rapid, sensitive, specific and quantitative, and has the potential of wide application for early diagnosis of hRSV infection and evaluation of the therapeutic effect.

Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years

PubMed Central

Collins, Peter L.; Melero, José A.

2011-01-01

Human respiratory syncytial virus (RSV) is a ubiquitous pathogen that infects everyone worldwide early in life and is a leading cause of severe lower respiratory tract disease in the pediatric population as well as in the elderly and in profoundly immunosuppressed individuals. RSV is an enveloped, nonsegmented negative-sense RNA virus that is classified in Family Paramyxoviridae and is one of its more complex members. Although the replicative cycle of RSV follows the general pattern of the Paramyxoviridae, it encodes additional proteins. Two of these (NS1 and NS2) inhibit the host type I and type III interferon (IFN) responses, among other functions, and another gene encodes two novel RNA synthesis factors (M2-1 and M2-2). The attachment (G) glycoprotein also exhibits unusual features, such as high sequence variability, extensive glycosylation, cytokine mimicry, and a shed form that helps the virus evade neutralizing antibodies. RSV is notable for being able to efficiently infect early in life, with the peak of hospitalization at 2–3 months of age. It also is notable for the ability to reinfect symptomatically throughout life without need for significant antigenic change, although immunity from prior infection reduces disease. It is widely thought that re-infection is due to an ability of RSV to inhibit or subvert the host immune response. Mechanisms of viral pathogenesis remain controversial. RSV is notable for a historic, tragic pediatric vaccine failure involving a formalin-inactivated virus preparation that was evaluated in the 1960’s and that was poorly protective and paradoxically primed for enhanced RSV disease. RSV also is notable for the development of a successful strategy for passive immunoprophylaxis of high-risk infants using RSV-neutralizing antibodies. Vaccines and new antiviral drugs are in pre-clinical and clinical development, but controlling RSV remains a formidable challenge. PMID:21963675

Bronchiolitis - discharge

MedlinePlus

... bronchiolitis. Your health care provider may prescribe such medicine for your child. DO NOT give your child decongestant nose drops, antihistamines, or any other cold medicines unless your child's doctor tells you to. When to Call the ...

Use of palivizumab with other infection control measures to control respiratory syncytial virus outbreaks in neonatal care units.

PubMed

Hammoud, Majeda S; Al-Taiar, Abdullah; Raina, Aditiya; Elsori, Dalal; Al-Qabandi, Sarah; Al-Essa, Mazen

2016-10-01

No guidelines exist on the use of palivizumab during outbreaks of Respiratory Syncytial Virus (RSV) in Neonatal Intensive Care Units (NICUs). We aimed to describe an outbreak of RSV in NICU settings and the role of palivizumab in controlling the outbreak. The index case was a 30-day-old premature infant. During the outbreak, 13 cases of RSV were confirmed by RT-PCR. All infants in the NICU received palivizumab after RSV diagnosis. Of the 13 cases, seven were male; and the median (interquartile) of birth weight was 1585 (IQR: 1480-1705) g. All cases were premature under 34-weeks-gestation. Age at onset of disease varies between 10 and 160 days. Only four cases occurred after administering palivizumab and applying other infection control measures. During nosocomial outbreaks of RSV, administration of palivizumab to all infants in NICU appears to be rational and may help contain outbreaks. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of hospital and community-acquired respiratory syncytial virus in children with severe lower respiratory tract infections in Ho Chi Minh City, Vietnam, 2010

PubMed Central

Tuan, Tran Anh; Thanh, Tran Tan; Hai, Nguyen thi Thanh; Tinh, Le Binh Bao; Kim, Le thi Ngoc; Do, Lien Anh Ha; Chinh B'Krong, Nguyen thi Thuy; Tham, Nguyen thi; Hang, Vu thi Ty; Merson, Laura; Farrar, Jeremy; Thuong, Tang Chi; de Jong, Menno D; Schultsz, Constance; van Doorn, H Rogier

2015-01-01

Background Human respiratory syncytial virus (RSV) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce. Methods During a 1-year surveillance study in 2010, we took serial samples from children admitted to the Emergency Unit of the Respiratory Ward of Children's Hospital 1 in Ho Chi Minh City, Vietnam. RSV was detected within 72 hours of admission to the ward in 26% (376/1439; RSV A: n = 320; RSV B: n = 54; and RSV A and B: n = 2). Among those negative in the first 72 hours after admission, 6·6% (25/377) acquired nosocomial RSV infection during hospitalization (RSV A: n = 22; and RSV B: n = 3). Results Children with nosocomial RSV infection were younger (P = 0·001) and had a longer duration of hospitalization (P < 0·001). The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without (P < 0·001). Phylogenetic analysis of partial G gene sequences obtained from 79% (316/401) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant (A NA1: n = 275; A GA5: n = 5; B BA3: n = 3; B BA9: n = 26; and B BA10: n = 7). The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam, previously. Conclusion Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen, data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam. PMID:25702707

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice.

PubMed

Henderson, F W; Clyde, W A; Collier, A M; Denny, F W; Senior, R J; Sheaffer, C I; Conley, W G; Christian, R M

1979-08-01

To develop a broad understanding of the causes and patterns of occurrence of wheezing associated respiratory infections, we analyzed data from an 11-year study of acute lower respiratory illness in a pediatric practice. Although half of the WARI occurred in children less than 2 years of age, wheezing continued to be observed in 19% of children greater than 9 years of age who had lower respiratory illness. Males experienced LRI 1.25 times more often than did females; the relative risk of males for WARI was 1.35. A nonbacterial pathogen was recovered from 21% of patients with WARI; respiratory syncytial virus, parainfluenza virus types 1 and 3, adenoviruses, and Mycoplasma pneumoniae accounted for 81% of the isolates. Patient age influenced the pattern of recovery of these agents. The most common cause of WARI in children under 5 years of age was RSV whereas Mycoplasma pneumoniae was the most frequent isolate from school age children with wheezing illness. The data expand our understanding of the causes of WARI and are useful to diagnosticians and to researchers interested in the control of lower respiratory disease.

Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine

2010-01-20

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by themore » fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the

Comparative epidemiology of human metapneumovirus- and respiratory syncytial virus-associated hospitalizations in Guatemala

PubMed Central

McCracken, John P; Arvelo, Wences; Ortíz, José; Reyes, Lissette; Gray, Jennifer; Estevez, Alejandra; Castañeda, Oscar; Langley, Gayle; Lindblade, Kim A

2014-01-01

Background Human metapneumovirus (HMPV) is an important cause of acute respiratory infections (ARI), but little is known about how it compares with respiratory syncytial virus (RSV) in Central America. Objectives In this study, we describe hospitalized cases of HMPV- and RSV-ARI in Guatemala. Methods We conducted surveillance at three hospitals (November 2007–December 2012) and tested nasopharyngeal and oropharyngeal swab specimens for HMPV and RSV using real-time reverse transcription-polymerase chain reaction. We calculated incidence rates, and compared the epidemiology and outcomes of HMPV-positive versus RSV-positive and RSV-HMPV-negative cases. Results We enrolled and tested specimens from 6288 ARI cases; 596 (9%) were HMPV-positive and 1485 (24%) were RSV-positive. We observed a seasonal pattern of RSV but not HMPV. The proportion HMPV-positive was low (3%) and RSV-positive high (41%) for age <1 month, whereas these proportions were similar (∼20%) by age 2 years. The annual incidence of hospitalized HMPV-ARI was 102/100 000 children aged <5 years [95% confidence interval (CI): 75–178], 2·6/100 000 persons aged 5–17 years (95%CI: 1·2–5·0), and 2·6/100 000 persons aged ≥18 years (95%CI: 1·5–4·9). Among children aged <5 years, HMPV-positive cases were less severe than HMPV-RSV-negative cases after adjustment for confounders [odds ratio (OR) for intensive care = 0·63, 95% CI 0·47–0·84]; OR for death = 0·46, 95% CI 0·23–0·92). Conclusions Human metapneumovirus is a substantial contributor to ARI hospitalization in Guatemala, but HMPV hospitalizations are less frequent than RSV and, in young children, less severe than other etiologies. Preventive interventions should take into account the wide variation in incidence by age and unpredictable timing of incidence peaks. PMID:24761765

Human respiratory syncytial virus in children with lower respiratory tract infections or influenza-like illness and its co-infection characteristics with viruses and atypical bacteria in Hangzhou, China.

PubMed

Yu, Xinfen; Kou, Yu; Xia, Daozong; Li, Jun; Yang, Xuhui; Zhou, Yinyan; He, Xiaoyan

2015-08-01

Human respiratory syncytial virus (RSV) is the most important viral pathogen in children. However, its epidemic patterns and co-infection characteristics are not fully understood. We attempted to determine the level of genetic variation of RSV, and describe the prevalence and co-infection characteristics of RSV in Hangzhou during two epidemic seasons. Single respiratory samples from 1820 pediatric patients were screened for RSV and genotyped by RT-PCR and sequencing. In all RSV positive specimens, we screened for viruses and atypical bacteria. Demographic and clinical information was recorded and analyzed. A total of 34.5% and 3.8% of samples from acute lower respiratory tract infections (ALRI) and influenza-like illness (ILI) were positive for RSV, respectively. Phylogenetic analysis revealed that 61.1% of the selected 167 RSV strains were NA1, 31.1% were BA, 3.6% were ON1, 2.4% were CB1, and 1.8% were NA3. A new genotype, BA11 was identified, which comprised 98.1% of BA strains in this study, while the rest were BA10. A total of 36.4% and 9.1% of RSV-positive children with ALRI and ILI respectively were found to be co-infected. Rhinovirus was the most common additional respiratory virus, followed by human metapneumovirus. Except for fever, no significant differences in other clinical presentation between the RSV mono-infection and co-infection groups were observed. The circulating RSV strains had high genetic variability with RSV-B showing a more local pattern. In ALRI cases, co-infection of RSV with other viruses or atypical bacteria has no significant effect on the clinical presentation except fever. Copyright © 2015 Elsevier B.V. All rights reserved.

Hypertonic Saline for the Treatment of Bronchiolitis in Infants and Young Children: A Critical Review of the Literature

PubMed Central

Baron, Jeffrey

2016-01-01

Bronchiolitis, an infection of the lower respiratory tract, is the leading cause of infant and child hospitalization in the United States. Therapeutic options for management of bronchiolitis are limited. Hypertonic saline inhalation therapy has been studied in numerous clinical trials with mixed results. In 2014, the American Academy of Pediatrics (AAP) published updated guidelines on the diagnosis and management of bronchiolitis, which include new recommendations on the use of hypertonic saline. We reviewed all published clinical trials mentioned in the 2014 AAP guidelines, as well as additional trials published since the guidelines, and critically evaluated each trial to determine efficacy, safety, and expectations of hypertonic saline inhalation therapy. A total of 2682 infants were studied over the course of 22 clinical trials. Nine trials were carried out in the outpatient/clinic/emergency department and 13 in the inpatient setting. We agree with the AAP guidelines regarding the recommendation to use nebulized hypertonic saline for infants hospitalized with bronchiolitis, with the expectation of reducing bronchiolitis scores and length of stay when it is expected to last more than 72 hours. However, we also believe there might be an advantage for hypertonic saline in reducing admission rates from the emergency department, based on close examination of the results of recent trials. This review also highlights important gaps in the available literature that need to be addressed in order to define the role of inhaled hypertonic saline therapy. PMID:26997926

[Respiratory syncytial virus outbreak in a tertiary hospital Neonatal Intensive Care Unit].

PubMed

Moreno Parejo, Carlos; Morillo García, Aurea; Lozano Domínguez, Carmen; Carreño Ochoa, Concepción; Aznar Martín, Javier; Conde Herrera, Manuel

2016-09-01

Investigation and control of a respiratory syncytial virus (RSV) outbreak that affected the Neonatal Intensive Care Unit (NICU) of a university hospital from October to December 2012. Cohort study of children admitted to the NICU. The infection attack rate was calculated. A descriptive analysis of the cases and a multivariate analysis was performed using the variables that were shown to be risk factors for RSV infection. Preventive measures taken were: contact isolation; hand hygiene training and observation; exclusivity of a health team of nurses and physicians for positive cases, restrictions on visitor numbers; surveillance RSV testing, and palivizumab prophylaxis. The outbreak had three epidemic waves and 20 positive cases out of a total of 48 children admitted. The overall attack rate was 42%. Half of positive cases were children, with a median age of 36 days (p25=22, p75=58). The independent risk factors for RSV infection were birth weight below 1000 grams (OR=23.5; P=.002) and to have another nosocomial infection the week before the diagnosis of RSV infection (OR=19.98; P=.016). It was an outbreak with a high number of cases, due to the delay in notification, prolonged RSV carrier status, and low adherence to hand hygiene practice, which favoured the cross-transmission of infection. The most effective preventive measures were direct observation of hand hygiene and supervision of isolation measures. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010-2011.

PubMed

Moyes, Jocelyn; Cohen, Cheryl; Pretorius, Marthi; Groome, Michelle; von Gottberg, Anne; Wolter, Nicole; Walaza, Sibongile; Haffejee, Sumayya; Chhagan, Meera; Naby, Fathima; Cohen, Adam L; Tempia, Stefano; Kahn, Kathleen; Dawood, Halima; Venter, Marietjie; Madhi, Shabir A

2013-12-15

There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Children aged <5 years admitted to sentinel surveillance hospitals with physician-diagnosed neonatal sepsis or ALRTI were enrolled. Nasopharyngeal aspirates were tested by multiplex real-time polymerase chain reaction assays for RSV and other viruses. Associations between possible risk factors and severe outcomes for RSV infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

Clinical characteristics and direct medical cost of respiratory syncytial virus infection in children hospitalized in Suzhou, China.

PubMed

Zhang, Tao; Zhu, Qiuli; Zhang, Xuelan; Ding, Yunfang; Steinhoff, Mark; Black, Steven; Zhao, Genming

2014-04-01

There have been few studies on children hospitalized with respiratory syncytial virus (RSV) published from mainland China. We performed a retrospective review of medical charts to describe the epidemiology, clinical features and direct medical cost of laboratory-proven RSV children hospitalized in Suzhou, China. Testing is routine for RSV for children admitted to the respiratory ward at Suzhou University Children's Hospital. We performed a retrospective study on children with documented RSV infection hospitalized at Suzhou University Children Hospital during 2005-2009 using a structured chart review instrument. A total of 2721 hospitalized children (15.0% of those tested) were positive by immunofluorescent assay for RSV during 2005-2009, and 64.0% of them were male. Eighty-seven percentage of the RSV-infected children were 2 years old and younger, and 56.6% were ≤ 6 months of age. The median length of hospital stay was 8 days. Of the RSV-infected children, 92.5% developed pneumonia and 21.8% experienced wheezing. In total, 49 (5.1%) of RSV-positive children were transferred to the ICU. Children ≤ 6 months old and who had congenital heart disease had higher risk of severe RSV disease. The mean cost of each RSV-related hospitalization was US$571.8 (US$909.6 for children referred to ICU and US$565.4 for those cared for on the wards). Multivariable logistic regression showed that compared with the ≤ 6 months children, those aged >6 months old had higher hospitalization cost; children with respiratory distress or with chronic lung diseases tended to have higher hospitalization costs than others. RSV infections and severe RSV diseases mostly occurred in early infancy. The direct medical cost was high relative to family income. Effective strategies of RSV immunization of young children in China may be beneficial in addressing this disease burden.

Detection of viruses and atypical bacteria associated with acute respiratory infection of children in Hubei, China.

PubMed

Wu, Zegang; Li, Yan; Gu, Jian; Zheng, Hongyun; Tong, Yongqing; Wu, Qing

2014-02-01

Acute respiratory infection is the major cause of disease and death in children, particularly in developing countries. However, the spectrum of pathogenic viruses and atypical bacteria that exist in many of these countries remains incompletely characterized. The aim of this study was to examine the spectrum of pathogenic viruses and atypical bacteria associated with acute respiratory infection in children under the age of 16. A total of 10 435 serum sera specimens were collected from hospitalized children presenting with acute respiratory infection symptoms. Indirect immunofluorescence assays were performed to detect immunoglobulin M antibodies against nine common pathogens: mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila, coxiella burnetii and chamydophila pneumonia. Of the 10 435 specimens examined, 7046 tested positive for at least one pathogen. Among all of the tested pathogens, mycoplasma pneumonia had the highest detection rate (56.9%). Influenza virus A and influenza virus B epidemics occurred during both winter and summer. The detection rate of respiratory syncytial virus and adenovirus was higher in spring. Cases of mixed infection were more complex: 4136 specimens (39.6%) tested positive for ≥2 pathogens. There were statistically significant difference in detection rates of mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila and chamydophila pneumonia among different age groups (P < 0.05). The most common pathogens causing acute respiratory infection among children in Hubei of China were mycoplasma pneumonia, influenza virus B and respiratory syncytial virus. The detection rates for each pathogen displayed specific seasonal and age group variations. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

PubMed

Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

2016-06-01

Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

PubMed Central

Nair, Harish; Nokes, D James; Gessner, Bradford D; Dherani, Mukesh; Madhi, Shabir A; Singleton, Rosalyn J; O'Brien, Katherine L; Roca, Anna; Wright, Peter F; Bruce, Nigel; Chandran, Aruna; Theodoratou, Evropi; Sutanto, Agustinus; Sedyaningsih, Endang R; Ngama, Mwanajuma; Munywoki, Patrick K; Kartasasmita, Cissy; Simões, Eric AF; Rudan, Igor; Weber, Martin W; Campbell, Harry

2010-01-01

Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation. PMID:20399493

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis.

PubMed

Nair, Harish; Nokes, D James; Gessner, Bradford D; Dherani, Mukesh; Madhi, Shabir A; Singleton, Rosalyn J; O'Brien, Katherine L; Roca, Anna; Wright, Peter F; Bruce, Nigel; Chandran, Aruna; Theodoratou, Evropi; Sutanto, Agustinus; Sedyaningsih, Endang R; Ngama, Mwanajuma; Munywoki, Patrick K; Kartasasmita, Cissy; Simões, Eric A F; Rudan, Igor; Weber, Martin W; Campbell, Harry

2010-05-01

The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. In 2005, an estimated 33.8 (95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000-199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. WHO; Bill & Melinda Gates Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.

Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children.

PubMed

Buchholz, Ursula J; Cunningham, Coleen K; Muresan, Petronella; Gnanashanmugam, Devasena; Sato, Paul; Siberry, George K; Rexroad, Vivian; Valentine, Megan; Perlowski, Charlotte; Schappell, Elizabeth; Thumar, Bhagvinji; Luongo, Cindy; Barr, Emily; Aziz, Mariam; Yogev, Ram; Spector, Stephen A; Collins, Peter L; McFarland, Elizabeth J; Karron, Ruth A

2018-04-11

Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation. RSV-seronegative 6-24-month-old children received an intranasal dose of 105.3 plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285). RSV serum neutralizing antibody titers before and 56 days after vaccination, vaccine virus infectivity (defined as vaccine virus shedding detectable in nasal wash and/or a ≥4-fold rise in serum antibodies), reactogenicity, and genetic stability were assessed. During the following RSV transmission season, participants were monitored for respiratory illness, with serum antibody titers measured before and after the season. A total of 85% of vaccinees were infected with RSVcps2 (median peak titer, 0.5 log10 PFU/mL by culture and 2.9 log10 copies/mL by polymerase chain reaction analysis); 77% shed vaccine virus, and 59% developed a ≥4-fold rise in RSV-serum neutralizing antibody titers. Respiratory tract and/or febrile illness occurred at the same rate (50%) in the vaccine and placebo groups. Deattenuation was not detected at either of 2 stabilized mutation sites. RSVcps2 was well tolerated and moderately immunogenic and had increased genetic stability in 6-24-month-old RSV-seronegative children. NCT01852266 and NCT01968083.

Chimeric Bovine/Human Parainfluenza Virus Type 3 Expressing Respiratory Syncytial Virus (RSV) F Glycoprotein: Effect of Insert Position on Expression, Replication, Immunogenicity, Stability, and Protection against RSV Infection

PubMed Central

Munir, Shirin; Amaro-Carambot, Emerito; Surman, Sonja; Mackow, Natalie; Yang, Lijuan; Buchholz, Ursula J.; Collins, Peter L.; Schaap-Nutt, Anne

2014-01-01

ABSTRACT A recombinant chimeric bovine/human parainfluenza type 3 virus (rB/HPIV3) vector expressing the respiratory syncytial virus (RSV) fusion F glycoprotein previously exhibited disappointing levels of RSV F immunogenicity and genetic stability in children (D. Bernstein et al., Pediatr. Infect. Dis. J. 31:109–114, 2012; C.-F. Yang et al., Vaccine 31:2822–2827, 2013). To investigate parameters that might affect vaccine performance and stability, we constructed and characterized rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions. There was a 30- to 69-fold gradient in RSV F expression from the first to the sixth position. The inserts moderately attenuated vector replication in vitro and in the upper and lower respiratory tracts of hamsters: this was not influenced by the level of RSV F expression and syncytium formation. Surprisingly, inserts in the second, third, and sixth positions conferred increased temperature sensitivity: this was greatest for the third position and was the most attenuating in vivo. Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6. Evaluation of insert stability suggested that RSV F is under selective pressure to be silenced during vector replication in vivo, but this was not exacerbated by a high level of RSV F expression and generally involved a small percentage of recovered vector. Vector passaged in vitro accumulated mutations in the HN open reading frame, causing a dramatic increase in plaque size that may have implications for vaccine production and immunogenicity. IMPORTANCE The research findings presented here will be instrumental for improving the design of a bivalent pediatric vaccine for respiratory syncytial virus and parainfluenza virus type 3, two major causes of severe respiratory tract infection in infants and young

Comparative analysis of the effects of two chest physical therapy interventions in patients with bronchiolitis during hospitalization period

PubMed Central

Remondini, Renata; dos Santos, Adriana Zamprônio; de Castro, Giselle; do Prado, Cristiane; da Silva, Luiz Vicente Ribeiro Ferreira

2014-01-01

Objective To evaluate and compare the effects of two chest physiotherapy interventions in patients hospitalized due to acute bronchiolitis. Methods Prospective randomized study with a sample of 83 calls for 29 patients aged between 3 months and 1 year hospitalized for acute bronchiolitis. Patients were distributed randomly into two groups: Group 1, submitted to postural drainage, tapping and tracheal aspiration; and Group 2, submitted to postural drainage, expiratory acceleration flow and tracheal aspiration. Assessments were made before and 10 and 60 minutes after the end of therapy. Patients also underwent drug treatment. The endpoint was to compare two physical therapy interventions as to clinical improvement in infants with acute bronchiolitis by means of oxygen saturation and the Respiratory Distress Assessment Instrument score. The parents/guardians was requested to answer a questionnaire about the treatment applied before the last evaluation in order to measure their satisfaction related to the interventions made. Results The groups were similar regarding the use of antibiotics and bronchodilators. A greater number of patients used corticosteroids in Group 2. A relevant improvement was observed on Respiratory Distress Assessment Instrument score with physical therapy, with reduction of the score 10 minutes after interventions, and the same score 60 minutes later, with no differences between techniques applied. There was no significant variation of pulse oximetry after chest physiotherapy. Most items assessed by the questionnaire had satisfactory answers. Conclusion No differences were observed between groups regarding the items assessed (time required to discharge from study, pulse oximetry in room air and disease severity according to the Respiratory Distress Assessment Instrument score). Parents answered positively about the effects of therapy in the majority of items in the questionnaire, both for the expiratory acceleration flow technique and for tapping

Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

PubMed Central

Foronjy, Robert F.; Dabo, Abdoulaye J.; Taggart, Clifford C.; Weldon, Sinead; Geraghty, Patrick

2014-01-01

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. PMID:24587397

Respiratory Syncytial Virus–Associated Mortality in Hospitalized Infants and Young Children

PubMed Central

Wilkes, Jacob; Korgenski, Kent; Sheng, Xiaoming

2015-01-01

BACKGROUND AND OBJECTIVE: Respiratory syncytial virus (RSV) is a common cause of pediatric hospitalization, but the mortality rate and estimated annual deaths are based on decades-old data. Our objective was to describe contemporary RSV-associated mortality in hospitalized infants and children aged <2 years. METHODS: We queried the Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID) for 2000, 2003, 2006, and 2009 and the Pediatric Health Information System (PHIS) administrative data from 2000 to 2011 for hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for RSV infection and mortality. RESULTS: The KID data sets identified 607 937 RSV-associated admissions and 550 deaths (9.0 deaths/10 000 admissions). The PHIS data set identified 264 721 RSV-associated admissions and 671 deaths (25.4 deaths/10 000 admissions) (P < .001 compared with the KID data set). The 2009 KID data set estimated 42.0 annual deaths (3.0 deaths/10 000 admissions) for those with a primary diagnosis of RSV. The PHIS data set identified 259 deaths with a primary diagnosis of RSV, with mortality rates peaking at 14.0/10 000 admissions in 2002 and 2003 and decreasing to 4.0/10 000 patients by 2011 (odds ratio: 0.27 [95% confidence interval: 0.14–0.52]). The majority of deaths in both the KID and PHIS data sets occurred in infants with complex chronic conditions and in those with other acute conditions such as sepsis that could have contributed to their deaths. CONCLUSIONS: Deaths associated with RSV are uncommon in the 21st century. Children with complex chronic conditions account for the majority of deaths, and the relative contribution of RSV infection to their deaths is unclear. PMID:25489019

Seasonal Timing of Infant Bronchiolitis, Apnea and Sudden Unexplained Infant Death

PubMed Central

Sloan, Chantel D.; Gebretsadik, Tebeb; Rosas-Salazar, Christian; Wu, Pingsheng; Carroll, Kecia N.; Mitchel, Edward; Anderson, Larry J.; Larkin, Emma K.; Hartert, Tina V.

2016-01-01

Rates of Sudden Unexplained Infant Death (SUID), bronchiolitis, and central apnea increase in winter in temperate climates. Though associations between these three conditions are suggested, more work is required to establish if there is a causal pathway linking bronchiolitis to SUID through inducing central apnea. Utilizing a large population-based cohort of infants studied over a 20-year period (n = 834,595, from birth years 1989–2009)), we analyzed ecological associations between timing of SUID cases, bronchiolitis, and apnea healthcare visits. Data were analyzed between 2013 and 2015. We used a Cox Proportional Hazards model to analyze possible interactions between maternal smoking and maternal asthma with infant bronchiolitis on time to SUID. SUID and bronchiolitis both occurred more frequently in winter. An increase in bronchiolitis clinical visits occurred within a few days prior to apnea visits. We found a temporal relationship between infant bronchiolitis and apnea. In contrast, no peak in SUID cases was seen during peaks of bronchiolitis. Among those without any bronchiolitis visits, maternal smoking was associated with an increased risk of SUID: Hazard Ratio (HR) of 2.38 (95% CI: 2.11, 2.67, p-value <0.001). Maternal asthma was associated with an increased risk of SUID among infants with at least one bronchiolitis visit: HR of 2.40 (95% CI: 1.04, 5.54, p-value = 0.04). Consistent trends between bronchiolitis, apnea, and SUID were not established due to small numbers of SUID cases. However, interaction analysis revealed potential differential associations of bronchiolitis and SUID by maternal smoking, maternal asthma status. PMID:27404386

Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.

PubMed

Cunningham, Steve; Rodriguez, Aryelly; Adams, Tim; Boyd, Kathleen A; Butcher, Isabella; Enderby, Beth; MacLean, Morag; McCormick, Jonathan; Paton, James Y; Wee, Fiona; Thomas, Huw; Riding, Kay; Turner, Steve W; Williams, Chris; McIntosh, Emma; Lewis, Steff C

2015-09-12

The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study [BIDS]). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation [SpO2] <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference -1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care

The Fecal Microbiota Profile and Bronchiolitis in Infants

PubMed Central

Linnemann, Rachel W.; Mansbach, Jonathan M.; Ajami, Nadim J.; Espinola, Janice A.; Petrosino, Joseph F.; Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Thompson, Amy D.; Camargo, Carlos A.

2016-01-01

BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. PMID:27354456

Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models.

PubMed

White, L J; Mandl, J N; Gomes, M G M; Bodley-Tickell, A T; Cane, P A; Perez-Brena, P; Aguilar, J C; Siqueira, M M; Portes, S A; Straliotto, S M; Waris, M; Nokes, D J; Medley, G F

2007-09-01

The nature and role of re-infection and partial immunity are likely to be important determinants of the transmission dynamics of human respiratory syncytial virus (hRSV). We propose a single model structure that captures four possible host responses to infection and subsequent reinfection: partial susceptibility, altered infection duration, reduced infectiousness and temporary immunity (which might be partial). The magnitude of these responses is determined by four homotopy parameters, and by setting some of these parameters to extreme values we generate a set of eight nested, deterministic transmission models. In order to investigate hRSV transmission dynamics, we applied these models to incidence data from eight international locations. Seasonality is included as cyclic variation in transmission. Parameters associated with the natural history of the infection were assumed to be independent of geographic location, while others, such as those associated with seasonality, were assumed location specific. Models incorporating either of the two extreme assumptions for immunity (none or solid and lifelong) were unable to reproduce the observed dynamics. Model fits with either waning or partial immunity to disease or both were visually comparable. The best fitting structure was a lifelong partial immunity to both disease and infection. Observed patterns were reproduced by stochastic simulations using the parameter values estimated from the deterministic models.

Incidence and risk factors of respiratory syncytial virus-related hospitalizations in premature infants in Germany.

PubMed

Liese, Johannes G; Grill, Eva; Fischer, Birgit; Roeckl-Wiedmann, Irmgard; Carr, David; Belohradsky, Bernd H

2003-04-01

Premature infants have an increased risk of developing complicated respiratory syncytial virus (RSV) infections. Epidemiological data on RSV-related hospitalizations are a prerequisite to develop guidelines for the use of preventive measures. The objective of this study was to determine incidence and risk factors of RSV-related rehospitalizations (RSV-RH) of premature infants. We recruited 1,103 infants with a gestational age of less than 35 weeks, primarily admitted to nine neonatologic care units in southern Germany between Nov. 1, 1998 and Oct. 31, 1999. Questionnaires were sent to all parents of infants discharged from neonatal care units to determine the risk of rehospitalization for acute respiratory infections (ARI-RH) and RSV-RH in the 1999-2000 season. The questionnaire response rate was 68.4%. The 717 included infants of the responders had a mean gestational age of 31.6 weeks (Range: 23-35) and a mean birth weight of 1,747 g (range: 430-4,050 g). The risk for an ARI-RH was 10.6% and the risk for RSV-RH 5.2% during the observation period. Premature infants with chronic lung disease (CLD) had a probability of 24.5% for ARI-RH and of 15% for RSV-RH. The following factors were independently associated with an increased risk of RSV-RH: male gender (adjusted Odds-Ratio (OR): 8.7; 95% confidence interval (CI): 2.6-29.1), chronic lung disease (OR: 3.99; 95%CI: 1.4-11.2), discharge between October and December (OR: 2.1; 95%CI: 0.99-4.4), day-care attendance of siblings (OR: 3.9; 95%CI: 1.9-8.3). The risk for RSV rehospitalization among premature infants discharged from neonatal care facilities in southern Germany was low. Additional risk factors and high costs of prophylaxis have to be considered when infants are selected for RSV prophylaxis using monoclonal antibodies.

Palivizumab prophylaxis for respiratory syncytial virus in infants with cystic fibrosis: is there a need?

PubMed

Bjornson, Candice; Chan, Parco; Li, Abby; Paes, Bosco; Lanctôt, Krista L; Mitchell, Ian

2018-06-01

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study's objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged < 2 years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ 2 and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B) = 0.23 [0.11-0.49], p < 0.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; t = 2.39 [df = 7], p = 0.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (t = 3.52 [df = 15], p = 0.003) and hospital LOS (t = 2.11 [df = 52], p = 0.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups.

Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie

2004-12-05

The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95%more » of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells.« less

Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil.

PubMed

Gurgel, Ricardo Queiroz; Bezerra, Patrícia Gomes de Matos; Duarte, Maria do Carmo Menezes Bezerra; Moura, Adriana Ávila; Souza, Edna Lucia; Silva, Luciana Sobral da Silveira; Suzuki, Claudia Eiko; Peixoto, Rodrigo Buzzatti

2016-04-01

Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.

Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation.

PubMed

Jaramillo, Andrés; Fernández, Félix G; Kuo, Elbert Y; Trulock, Elbert P; Patterson, G A; Mohanakumar, T

2005-02-01

Lung transplantation is recognized as the only viable treatment option in a variety of end-stage pulmonary diseases. However, the long-term survival after lung transplantation is limited by the development of obliterative bronchiolitis, and its clinical correlate bronchiolitis obliterans syndrome (BOS), which is considered to represent chronic lung allograft rejection. Histopathologically, BOS is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The specific etiology and pathogenesis of BOS are not well understood. The current premise is that BOS represents a common lesion in which different inflammatory insults such as ischemia-reperfusion, rejection, and infection can lead to a similar histological and clinical outcome. However, the low incidence of BOS in non-transplanted individuals and the observation that early development of BOS is predicted by the frequency and severity of acute rejection episodes indicate that alloimmune-dependent mechanisms play a crucial role in the pathogenesis of BOS. The evidence presented in this review indicates that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the lung allograft. This process is aggravated by alloimmune-independent mechanisms such as ischemia-reperfusion and infection. Currently, treatment of BOS is frequently unsuccessful. Therefore, a better understanding of the immunopathogenesis of BOS is of paramount importance toward improving long-term patient and graft survival after lung transplantation.

Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

PubMed

Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

2015-03-01

The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

Design and Characterization of Epitope-Scaffold Immunogens That Present the Motavizumab Epitope from Respiratory Syncytial Virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLellan, Jason S.; Correia, Bruno E.; Chen, Man

2012-06-28

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potentmore » neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 {angstrom} resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.« less

Recombinant measles viruses expressing respiratory syncytial virus proteins induced virus-specific CTL responses in cotton rats.

PubMed

Yamaji, Yoshiaki; Nakayama, Tetsuo

2014-07-31

Respiratory syncytial virus (RSV) is a common cause of serious lower respiratory tract illnesses in infants. Natural infections with RSV provide limited protection against reinfection because of inefficient immunological responses that do not induce long-term memory. RSV natural infection has been shown to induce unbalanced immune response. The effective clearance of RSV is known to require the induction of a balanced Th1/Th2 immune response, which involves the induction of cytotoxic T lymphocytes (CTL). In our previous study, recombinant AIK-C measles vaccine strains MVAIK/RSV/F and MVAIK/RSV/G were developed, which expressed the RSV fusion (F) protein or glycoprotein (G). These recombinant viruses elicited antibody responses against RSV in cotton rats, and no infectious virus was recovered, but small amounts of infiltration of inflammatory cells were observed in the lungs following RSV challenge. In the present study, recombinant AIK-C measles vaccine strains MVAIK/RSV/M2-1 and MVAIK/RSV/NP were developed, expressing RSV M2-1 or Nucleoprotein (NP), respectively. These viruses exhibited temperature-sensitivity (ts), which was derived from AIK-C, and expressed respective RSV antigens. The intramuscular inoculation of cotton rats with the recombinant measles virus led to the induction of CD8(+) IFN-γ(+) cells. No infectious virus was recovered from a lung homogenate following the challenge. A Histological examination of the lungs revealed a significant reduction in inflammatory reactions without alveolar damage. These results support the recombinant measles viruses being effective vaccine candidates against RSV that induce RSV-specific CTL responses with or without the development of an antibody response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.

PubMed

McLellan, Jason S; Correia, Bruno E; Chen, Man; Yang, Yongping; Graham, Barney S; Schief, William R; Kwong, Peter D

2011-06-24

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.

A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice.

PubMed

Céspedes, Pablo F; Rey-Jurado, Emma; Espinoza, Janyra A; Rivera, Claudia A; Canedo-Marroquín, Gisela; Bueno, Susan M; Kalergis, Alexis M

2017-02-01

Human respiratory syncytial virus (hRSV) is a major health burden worldwide, causing the majority of hospitalizations in children under two years old due to bronchiolitis and pneumonia. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that take place throughout the patient life. Although significant efforts have been invested worldwide, currently there are no licensed vaccines to prevent hRSV infection. Here, we describe that a recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV) confers protective immunity to the virus in mice. Our results show that a single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×10 7 plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8. Compared to unimmunized infected controls, vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages, parameters that are characteristic of hRSV infection in mice. Also, ex vivo re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-γ and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8 + and CD4 + T cell response capable of both restraining viral spread and preventing damage of the lungs. All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bordetella Pertussis is an Uncommon Pathogen in Children Hospitalized with Bronchiolitis During the Winter Season

PubMed Central

Piedra, Pedro A.; Mansbach, Jonathan M.; Jewell, Alan M.; Thakar, Sneha D.; Grant, Cameron C.; Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A.

2015-01-01

Background In the United States (U.S.), Bordetella pertussis incidence has increased. Cough and apnea are common findings in pertussis and also in bronchiolitis, the most common cause of hospitalization in U.S. infants. The objective was to determine the prevalence of B. pertussis infection in children hospitalized with bronchiolitis and to describe its clinical course. Methods Children hospitalized with bronchiolitis and age <2 years were eligible for a prospective, multicenter cohort study during three consecutive winter seasons (November to March) from 2007 to 2010. 16 sites in 12 states participated using a standardized enrollment protocol. Families were asked the 2010 Centers for Disease Control and Prevention (CDC) pertussis classification questions. Nasopharyngeal aspirates were obtained and tested by real time polymerase chain reaction for 16 viruses, Mycoplama pneumoniae and B. pertussis. Results 2068 (94%) of 2,207 children had one or more respiratory pathogens. B. pertussis was identified in 4 children (0.2%; 95% CI, 0.1–0.5%) with 3 having a viral co-infection. All 4 were younger than four months; 2 met the CDC definition of probable pertussis, and 3 had received at least one dose of an acellular pertussis vaccine. During the hospitalization, 2 had paroxysmal cough, 1 required ICU care, and the median length of stay was 13 days. Conclusion Our data support that B. pertussis is an uncommon pathogen in U.S. children hospitalized with bronchiolitis in the winter. Making a diagnosis of pertussis can be challenging because the disease can be atypical, and may not meet the CDC definition of probable infection. PMID:25970109

A model of the costs of community and nosocomial pediatric respiratory syncytial virus infections in Canadian hospitals

PubMed Central

Jacobs, Philip; Lier, Douglas; Gooch, Katherine; Buesch, Katharina; Lorimer, Michelle; Mitchell, Ian

2013-01-01

BACKGROUND: Approximately one in 10 hospitalized patients will acquire a nosocomial infection (NI) after admission to hospital, of which 71% are due to respiratory viruses, including the respiratory syncytial virus (RSV). NIs are concerning and lead to prolonged hospitalizations. The economics of NIs are typically described in generalized terms and specific cost data are lacking. OBJECTIVE: To develop an evidence-based model for predicting the risk and cost of nosocomial RSV infection in pediatric settings. METHODS: A model was developed, from a Canadian perspective, to capture all costs related to an RSV infection hospitalization, including the risk and cost of an NI, diagnostic testing and infection control. All data inputs were derived from published literature. Deterministic sensitivity analyses were performed to evaluate the uncertainty associated with the estimates and to explore the impact of changes to key variables. A probabilistic sensitivity analysis was performed to estimate a confidence interval for the overall cost estimate. RESULTS: The estimated cost of nosocomial RSV infection adds approximately 30.5% to the hospitalization costs for the treatment of community-acquired severe RSV infection. The net benefits of the prevention activities were estimated to be equivalent to 9% of the total RSV-related costs. Changes in the estimated hospital infection transmission rates did not have a significant impact on the base-case estimate. CONCLUSIONS: The risk and cost of nosocomial RSV infection contributes to the overall burden of RSV. The present model, which was developed to estimate this burden, can be adapted to other countries with different disease epidemiology, costs and hospital infection transmission rates. PMID:24421788

Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France.

PubMed

Loubet, P; Lenzi, N; Valette, M; Foulongne, V; Krivine, A; Houhou, N; Lagathu, G; Rogez, S; Alain, S; Duval, X; Galtier, F; Postil, D; Tattevin, P; Vanhems, P; Carrat, F; Lina, B; Launay, O

2017-04-01

The aim of this study was to analyse characteristics and outcome of respiratory syncytial virus (RSV) infection in adults hospitalized with influenza-like illness (ILI). Patients hospitalized with ILI were included in this prospective, multicentre study carried out in six French hospitals during three consecutive influenza seasons (2012-2015). RSV and other respiratory viruses were detected by multiplex PCR in nasopharyngeal swabs. Risk factors for RSV infection were identified by backward stepwise logistic regression analysis. A total of 1452 patients hospitalized with ILI were included, of whom 59% (861/1452) were >65 years and 83% (1211/1452) had underlying chronic illnesses. RSV was detected in 4% (59/1452), and influenza virus in 39% (566/1452). Risk factors for RSV infection were cancer (adjusted OR 2.1, 95% CI 1.1-4.1, p 0.04), and immunosuppressive treatment (adjusted OR 2.0, 95% CI 1.1-3.8, p 0.03). Patients with RSV had a median length of stay of 9 days (6-25), and 57% of them (30/53) had complications, including pneumonia (23/53, 44%) and respiratory failure (15/53, 28%). Fifteen per cent (8/53) were admitted to an intensive care unit, and the in-hospital mortality rate was 8% (4/53). Pneumonia was more likely to occur in patients with RSV than in patients with RSV-negative ILI (44% (23/53) versus 26% (362/1393), p 0.006) or with influenza virus infection (44% versus 28% (157/560), p 0.02). RSV is an infrequent cause of ILI during periods of influenza virus circulation but can cause severe complications in hospitalized adults. Risk factors for RSV detection in adults hospitalized with ILI include cancer and immunosuppressive treatment. Specific immunization and antiviral therapy might benefit patients at risk. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Use of laboratory and administrative data to understand the potential impact of human parainfluenza virus 4 on cases of bronchiolitis, croup, and pneumonia in Alberta, Canada.

PubMed

Fathima, Sumana; Simmonds, Kimberley; Invik, Jesse; Scott, Allison N; Drews, Steven

2016-08-11

Human Parainfluenza Virus (hPIV) causes severe respiratory illness in infants and adults. Our study describes the association of hPIV1-4 with bronchiolitis, croup, and pneumonia using retrospective laboratory, administrative and public health data. Due to issues including the historic lack of hPIV4 in some commercial respiratory virus panels, the description of the impact of hPIV4 on croup, bronchiolitis, and pneumonia at population levels has often been limited. This study will use routine clinical laboratory data, and administrative data to provide a preliminary description of the impact of hPIV4 on these diseases in our population. A three year cohort of patients positive for hPIV was linked with data from physician visits and hospital admissions to define cases and hospitalization status. International Classification of Disease (ICD-9) codes were used to determine if cases had croup, bronchiolitis, and pneumonia. We also looked at differences in hospitalization status, age and gender among hPIV1-4. All statistical analysis was done using SPSS (Version 19.0.0, IBM Corp© 2010) and Graphpad Prism V6 (GraphPad Software, Inc., 2012). Only hPIV1 and hPIV4 specimens had positivity rates greater than 5 % of all specimens sent for respiratory virus panel testing. hPIV1 exhibited a biennial pattern while the pattern for hPIV3 was less interpretable due to lower positivity rates. Circulation patterns for hPIV2 and hPIV4 were not assessed due to the low positivity rates of theses specimens. From 2010 to 2013, there were 2300 hPIV cases with hPIV3 (46 %) being the most common, followed by hPIV1 (27 %), hPIV4 (16 %) and hPIV2 (11 %). The median age was 2 years for all hPIV types. Males were slightly greater than females for hPIV1 and hPIV2, with an equal distribution for hPIV3 and slightly more females than males for hPIV4. hPIV1 and hPIV2 had the highest or proportion of croup while hPIV3 and hPIV4 had the highest proportion of pneumonia. Within hPIV4 cases

Estimating influenza and respiratory syncytial virus-associated mortality in Western Kenya using health and demographic surveillance system data, 2007-2013.

PubMed

Emukule, Gideon O; Spreeuwenberg, Peter; Chaves, Sandra S; Mott, Joshua A; Tempia, Stefano; Bigogo, Godfrey; Nyawanda, Bryan; Nyaguara, Amek; Widdowson, Marc-Alain; van der Velden, Koos; Paget, John W

2017-01-01

Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa. We used the negative binomial regression method and the rate-difference method (i.e. deaths during low and high influenza/RSV activity months), to estimate excess mortality attributable to influenza and RSV using verbal autopsy data collected through a health and demographic surveillance system in Western Kenya, 2007-2013. Excess mortality rates were calculated for a) all-cause mortality, b) respiratory deaths (including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB) related deaths. Using the negative binomial regression method, the mean annual all-cause excess mortality rate associated with influenza and RSV was 14.1 (95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000 person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0-27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality rates associated with influenza were among ≥50 years, particularly among persons with TB (41.6[95% CI 0.0-122.7]); and with RSV were among <5 years. Using the rate-difference method, the excess mortality rate for influenza and RSV was 44.8 (95% CI 36.8-54.4) and 19.7 (95% CI 14.7-26.5) per 100,000 PY, respectively, for all-cause deaths; and 9.6 (95% CI 6.3-14.7) and 6.6 (95% CI 3.9-11.0) per 100,000 PY, respectively, for respiratory deaths. Our study shows a substantial excess mortality associated with influenza and RSV in Western Kenya, especially among children <5 years and older persons with TB, supporting recommendations for influenza vaccination and efforts to develop RSV vaccines.

Development of a questionnaire to assess the impact on parents of their infant’s bronchiolitis hospitalization

PubMed Central

2013-01-01

Background Bronchiolitis is a distressing respiratory condition and the most common cause of hospitalization during the first year of life. The hospitalization of an infant is a stressful event for parents and deserves careful consideration. The objective of this work was to develop and validate a self-administered instrument that comprehensively assesses the impact on parents of the hospitalization of their infant for bronchiolitis. Methods The Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©) was developed using a literature review and pre-study interviews with both parents and clinicians. For finalization and psychometric validation, it was included in a multicenter, longitudinal, observational study conducted in France. Parents of infants under the age of 1 year and hospitalized for bronchiolitis were asked to complete the questionnaire at hospital discharge, and 3 months after. Results Seven hundred and seven questionnaires were completed by the parents of the 463 eligible infants. After finalization, based on principal component analyses, the IBHQ included 30 core items allowing the calculation of 7 dimension core scores (Worries and distress; Fear for future; Guilt; Impact on daily organization; Physical impact; Impact on behavior with hospitalized infant; Financial impact), as well as 16 optional items, allowing the calculation of 5 optional dimension scores (Disturbed breastfeeding; Physical reaction of hospitalized infant; Impact on feeding; Impact on behavior with other infants; Siblings’ reaction). Internal consistency reliability and construct validity of the IBHQ were satisfactory. The highest impact was observed for “Worries and distress”, “Fear for future” and “Impact on daily organization” scores. Conclusions The IBHQ is a reliable and valid instrument for assessing the multifaceted impact on parents of the hospitalization of their infant for bronchiolitis. PMID:23849687

Sustainability in the AAP Bronchiolitis Quality Improvement Project.

PubMed

Shadman, Kristin A; Ralston, Shawn L; Garber, Matthew D; Eickhoff, Jens; Mussman, Grant M; Walley, Susan C; Rice-Conboy, Elizabeth; Coller, Ryan J

2017-11-01

Adherence to American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline recommendations improved significantly through the AAP's multiinstitutional collaborative, the Bronchiolitis Quality Improvement Project (BQIP). We assessed sustainability of improvements at participating institutions for 1 year following completion of the collaborative. Twenty-one multidisciplinary hospital-based teams provided monthly data for key inpatient bronchiolitis measures during baseline and intervention bronchiolitis seasons. Nine sites provided data in the season following completion of the collaborative. Encounters included children younger than 24 months who were hospitalized for bronchiolitis without comorbid chronic illness, prematurity, or intensive care. Changes between baseline-, intervention-, and sustainability-season data were assessed using generalized linear mixed-effects models with site-specific random effects. Differences between hospital characteristics, baseline performance, and initial improvement between sites that did and did not participate in the sustainability season were compared. A total of 2275 discharges were reviewed, comprising 995 baseline, 877 intervention, and 403 sustainability- season encounters. Improvements in all key bronchiolitis quality measures achieved during the intervention season were maintained during the sustainability season, and orders for intermittent pulse oximetry increased from 40.6% (95% confidence interval [CI], 22.8-61.1) to 79.2% (95% CI, 58.0- 91.3). Sites that did and did not participate in the sustainability season had similar characteristics. BQIP participating sites maintained improvements in key bronchiolitis quality measures for 1 year following the project's completion. This approach, which provided an evidence-based best-practice toolkit while building the quality-improvement capacity of local interdisciplinary teams, may support performance gains that persist beyond the active phase of the

Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.

PubMed

Flower, Mark; Nandakumar, Lakshmy; Singh, Mahendra; Wyld, David; Windsor, Morgan; Fielding, David

2017-05-01

As a modern phenomenon, there is currently limited understanding of the possible toxic effects and broader implications of electronic nicotine delivery systems (ENDS). Large volumes of aerosolized particles are inhaled during "vaping" and there are now an increasing number of case reports demonstrating toxic effects of ENDS, as well as human studies demonstrating impaired lung function in users. This article presents a case of respiratory bronchiolitis interstitial lung disease (RB-ILD) precipitated by vaping in a 33-year-old male with 10 pack years of traditional cigarette and prior treatment for mixed germ cell tumour. The patient had started vaping 10-15 times per day while continuing to smoke 10 traditional cigarettes per day. After 3 months of exposure to e-cigarette vapour, chest computed tomography demonstrated multiple new poorly defined pulmonary nodules with fluffy parenchyma opacification centred along the terminal bronchovascular units. Video-assisted thoracoscopy with lung biopsy of the right upper and right middle lobes was undertaken. The microscopic findings were overall consistent with RB-ILD. This case demonstrates toxicity with use of ENDS on open lung biopsy with resolution of radiographic findings on cessation. We believe that this is the first case where open lung biopsy has demonstrated this and our findings are consistent with RB-ILD.

Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

PubMed

Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

2017-07-15

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein

PubMed Central

Leemans, A.; De Schryver, M.; Van der Gucht, W.; Heykers, A.; Pintelon, I.; Hotard, A. L.; Moore, M. L.; Melero, J. A.; McLellan, J. S.; Graham, B. S.; Broadbent, L.; Power, U. F.; Caljon, G.; Cos, P.; Maes, L.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F

Structure and functional dynamics characterization of the ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domain by combining molecular dynamics with excited normal modes.

PubMed

Araujo, Gabriela C; Silva, Ricardo H T; Scott, Luis P B; Araujo, Alexandre S; Souza, Fatima P; de Oliveira, Ronaldo Junio

2016-12-01

The human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infection in children and elderly people worldwide. Its genome encodes 11 proteins including SH protein, whose functions are not well known. Studies show that SH protein increases RSV virulence degree and permeability to small compounds, suggesting it is involved in the formation of ion channels. The knowledge of SH structure and function is fundamental for a better understanding of its infection mechanism. The aim of this study was to model, characterize, and analyze the structural behavior of SH protein in the phospholipids bilayer environment. Molecular modeling of SH pentameric structure was performed, followed by traditional molecular dynamics (MD) simulations of the protein immersed in the lipid bilayer. Molecular dynamics with excited normal modes (MDeNM) was applied in the resulting system in order to investigate long time scale pore dynamics. MD simulations support that SH protein is stable in its pentameric form. Simulations also showed the presence of water molecules within the bilayer by density distribution, thus confirming that SH protein is a viroporin. This water transport was also observed in MDeNM studies with histidine residues of five chains (His22 and His51), playing a key role in pore permeability. The combination of traditional MD and MDeNM was a very efficient protocol to investigate functional conformational changes of transmembrane proteins that act as molecular channels. This protocol can support future investigations of drug candidates by acting on SH protein to inhibit viral infection. Graphical Abstract The ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domainᅟ.

Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

PubMed

Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

2016-01-01

The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3). From this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

A nuclear factor-κB signaling pathway via protein kinase C δ regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells

PubMed Central

Masaki, Tomoyuki; Kojima, Takashi; Okabayashi, Tamaki; Ogasawara, Noriko; Ohkuni, Tsuyoshi; Obata, Kazufumi; Takasawa, Akira; Murata, Masaki; Tanaka, Satoshi; Hirakawa, Satoshi; Fuchimoto, Jun; Ninomiya, Takafumi; Fujii, Nobuhiro; Tsutsumi, Hiroyuki; Himi, Tetsuo; Sawada, Norimasa

2011-01-01

Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma, and severe lower respiratory tract disease in infants and young children. The airway epithelium, which has a well-developed barrier regulated by tight junctions, is the first line of defense during respiratory virus infection. In upper airway human nasal epithelial cells (HNECs), however, the primary site of RSV infection, the mechanisms of replication and budding of RSV, and the epithelial cell responses, including the tight junctional barrier, remain unknown. To investigate the detailed mechanisms of replication and budding of RSV in HNECs and the epithelial cell responses, we established an RSV-infected model using human telomerase reverse transcriptase–-transfected HNECs. We first found that the expression and barrier function of tight junction molecules claudin-4 and occludin were markedly induced together with production of proinflammatory cytokines interleukin 8 and tumor necrosis factor-α in HNECs after RSV infection, and the induction of tight junction molecules possibly contributed to budding of RSV. Furthermore, the replication and budding of RSV and the epithelial cell responses in HNECs were regulated via a protein kinase C δ/hypoxia-inducible factor-1α/nuclear factor-κB pathway. The control of this pathway in HNECs may be useful not only for prevention of replication and budding of RSV, but also in therapy for RSV-induced respiratory pathogenesis. PMID:21562222

The discovery of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 1.

PubMed

Bond, Silas; Draffan, Alistair G; Fenner, Jennifer E; Lambert, John; Lim, Chin Yu; Lin, Bo; Luttick, Angela; Mitchell, Jeffrey P; Morton, Craig J; Nearn, Roland H; Sanford, Vanessa; Stanislawski, Pauline C; Tucker, Simon P

2015-02-15

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. Compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of A and B strains of RSV targeting the fusion glycoprotein. SAR was developed by systematic exploration of the phenyl (R(1)) and benzoyl (R(2)) groups. Furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted in active analogues with improved properties (aqueous solubility, protein binding and logD) and excellent rat pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17). Copyright © 2014 Elsevier Ltd. All rights reserved.

Antigenic relatedness between glycoproteins of human respiratory syncytial virus subgroups A and B: evaluation of the contributions of F and G glycoproteins to immunity.

PubMed Central

Johnson, P R; Olmsted, R A; Prince, G A; Murphy, B R; Alling, D W; Walsh, E E; Collins, P L

1987-01-01

The degree of antigenic relatedness between human respiratory syncytial virus (RSV) subgroups A and B was estimated from antibody responses induced in cotton rats by respiratory tract infection with RSV. Glycoprotein-specific enzyme-linked immunosorbent assays of antibody responses induced by RSV infection demonstrated that the F glycoproteins of subgroups A and B were antigenically closely related (relatedness, R approximately 50%), whereas the G glycoproteins were only distantly related (R approximately 5%). Intermediate levels of antigenic relatedness (R approximately 25%) were seen in neutralizing antibodies from cotton rats infected with RSV of the two subgroups. Immunity against the F glycoprotein of subgroup A, induced by vaccinia-A2-F, conferred a high level of protection which was of comparable magnitude against challenge by RSV of either subgroup. In comparison, immunity against the G glycoprotein of subgroup A, induced by vaccinia-A2-G, conferred less complete, but significant, protection. Importantly, in vaccinia-A2-G-immunized animals, suppression of homologous challenge virus replication was significantly greater (13-fold) than that observed for the heterologous virus. PMID:3305988

Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.

PubMed

Al-Saiedy, Mustafa; Gunasekara, Lasantha; Green, Francis; Pratt, Ryan; Chiu, Andrea; Yang, Ailian; Dennis, John; Pieron, Cora; Bjornson, Candice; Winston, Brent; Amrein, Matthias

2018-03-01

Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.

Comparison of the Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa ProFlu+™ assay for detecting influenza and respiratory syncytial viruses.

PubMed

Selvaraju, Suresh B; Bambach, Adrienne V; Leber, Amy L; Patru, Maria-Magdalena; Patel, Anami; Menegus, Marilyn A

2014-09-01

The relative performance of 2 widely used reverse transcription polymerase chain reaction (RT-PCR) assays, the Focus diagnostics Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa Proflu+™ assay, was evaluated using 735 prospectively and retrospectively collected nasopharyngeal swab specimens. Overall, the assays showed positive and negative agreements of 100% and 99.7% for influenza A, 98.1% and 99.9% for influenza B, and 99.3% and 99.5% for respiratory syncytial virus. The relative analytical sensitivity of the 2 assays was also similar. Copyright © 2014 Elsevier Inc. All rights reserved.

Respiratory syncytial virus infection disrupts monolayer integrity and function in cystic fibrosis airway cells.

PubMed

Kong, Michele; Maeng, Patrick; Hong, Jeong; Szczesniak, Rhonda; Sorscher, Eric; Sullender, Wayne; Clancy, John Paul

2013-09-19

Respiratory Syncytial Virus (RSV) infection is a common contributor to pulmonary symptoms in children with cystic fibrosis (CF). Here we examined RSV infection in immortalized bronchial epithelial cells (CFBE41o-) expressing wild-type (wt) or F508del cystic fibrosis transmembrane conductance regulator (CFTR), for monolayer integrity and RSV replication. CFBE41o- monolayers expressing wt or F508del CFTR were grown on permeable supports and inoculated with RSV A2 strain. Control experiments utilized UV-inactivated RSV and heat-killed RSV. Monolayer resistance and RSV production was monitored for up to six days post-infection. Within 24 h, a progressive decrease in monolayer resistance was observed in RSV infected F508del CFBE41o- cells, while the monolayer integrity of RSV infected wt CFTR CFBE41o- cells remained stable. RSV replication was necessary to disrupt F508del CFBE41o- monolayers as UV-irradiated and heat killed RSV had no effect on monolayer integrity, with an earlier and much more pronounced peak in RSV titer noted in F508del relative to wt CFTR-expressing cells. RSV infection of wt CFBE41o- monolayers also resulted in blunting of CFTR response. These findings identify an enhanced sensitivity of CFBE41o- cells expressing F508del CFTR to RSV infection, replication and monolayer disruption independent of the cellular immune response, and provide a novel mechanism by which cystic fibrosis airway epithelia are susceptible to RSV-dependent injury.

Multiplex detection of respiratory pathogens

DOEpatents

McBride, Mary [Brentwood, CA; Slezak, Thomas [Livermore, CA; Birch, James M [Albany, CA

2012-07-31

Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

Respiratory virus detection during hospitalisation for lower respiratory tract infection in children under 2 years in South Auckland, New Zealand.

PubMed

Trenholme, Adrian A; Best, Emma J; Vogel, Alison M; Stewart, Joanna M; Miller, Charissa J; Lennon, Diana R

2017-06-01

To describe respiratory virus detection in children under 2 years of age in a population admitted with lower respiratory infection and to assess correlation with measures of severity. Nasopharyngeal aspirates from infants admitted with lower respiratory tract infection (n = 1645) over a 3-year time period were tested by polymerase chain reaction. We collected epidemiological and clinical data on all children. We assessed the correlation of presence of virus with length of hospital stay, intensive care admission and consolidation on chest X-ray. Of the children admitted 34% were Maori, 43% Pacific and 75% lived in areas in the bottom quintile for socio-economic deprivation. A virus was found in 94% of those tested including 30% with multiple viruses. Picornavirus was present in 59% including 34% as the sole virus. Respiratory syncytial virus was found in 39%. Virus co-detection was not associated with length of stay, chest X-ray changes or intensive care unit admission. In this disadvantaged predominately Maori and Pacific population, picornavirus is commonly found as a sole virus, respiratory syncytial virus is frequent but immunisation preventable influenza is infrequent. We did not find that co-detection of viruses was linked to severity. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Development, implementation, and evaluation of a community- and hospital-based respiratory syncytial virus prophylaxis program.

PubMed

Bracht, Marianne; Heffer, Michael; O'Brien, Karel

2005-02-01

To implement and deliver a respiratory syncytial virus prophylaxis (RSVP) program in response to the Canadian Pediatric Society recommendations. A novel program was designed to provide inpatient RSVP for at-risk infants cared for in 1 tertiary care newborn intensive care unit (NICU). This inpatient program was part of a coordinated approach to RSVP, designed and implemented by 3 hospitals. An RSVP program logic model was created and used by a multidisciplinary team to evaluate the in-house program and identify areas of program activity requiring improvement. Following the 2000 to 2001 RSV season, a compliance and outcomes audit was performed in the tertiary center; 193 infants were enrolled in the RSVP program and 162 infants had received RSVP in the NICU [Mean = 1.64 doses]. Telephone follow-up with the parents of discharged infants identified that 159 infants (98%) had successfully completed their full course of RSVP. Using the RSVP program logic model, 5 areas for program improvement were identified including infant recruitment, patient transfer/discharge processes, product procurement, preparation/distribution/administration of doses, and healthcare team communication. Interdisciplinary collaboration is an important factor in the success of the RSVP program and has supported a consistent model of care for the delivery of RSVP. The program logic model provided a useful structure to systematically review the RSVP program in this organization.

Promising approaches for the treatment and prevention of viral respiratory illnesses.

PubMed

Papadopoulos, Nikolaos G; Megremis, Spyridon; Kitsioulis, Nikolaos A; Vangelatou, Olympia; West, Peter; Xepapadaki, Paraskevi

2017-10-01

Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs.

PubMed

Li, X; Botts, S; Morton, D; Knickerbocker, M J; Adler, R

2006-03-01

Accidental intra-airway exposure of dogs with pure oleic acid produced bronchiolitis obliterans and bronchopneumonia. Pulmonary changes included multifocal to coalescing necrosis of bronchioles and adjacent alveoli, hemorrhage, inflammation, and exudation of fibrin. Hyperplasia of bronchiolar and alveolar epithelial cells and proliferation of loose fibrovascular connective tissue formed polyps or plugs of variable size and shape. Polyps in the airways primarily consisted of fibroblasts with loose or myxoid stroma and were variably covered with attenuated epithelial cells. Some polyps had prominent vasculature, mixed inflammatory cell infiltration, and/or necrosis. Polyps or plugs variably effaced bronchioles and adjacent alveoli. The changes closely resembled human bronchiolitis obliterans-organizing pneumonia (BOOP). Controlled intra-airway delivery of oleic acid in dogs may be a potential animal model of obstructive pulmonary diseases such as BOOP or bronchiolitis obliterans.

Preclinical Characterization of PC786, an Inhaled Small-Molecule Respiratory Syncytial Virus L Protein Polymerase Inhibitor

PubMed Central

Coates, Matthew; Brookes, Daniel; Kim, Young-In; Allen, Heather; Fordyce, Euan A. F.; Meals, Elizabeth A.; Colley, Thomas; Ciana, Claire-Lise; Parra, Guillaume F.; Sherbukhin, Vladimir; Stockwell, Jennifer A.; Thomas, Jennifer C.; Hunt, S. Fraser; Anderson-Dring, Lauren; Onions, Stuart T.; Cass, Lindsey; Murray, Peter J.; Strong, Pete; DeVincenzo, John P.; Rapeport, Garth

2017-01-01

ABSTRACT Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Here we report the preclinical profiles of PC786, a potent nonnucleoside RSV L protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective antiviral activity against laboratory-adapted or clinical isolates of RSV-A (50% inhibitory concentration [IC50], <0.09 to 0.71 nM) and RSV-B (IC50, 1.3 to 50.6 nM), which were determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. The underlying inhibition of virus replication was confirmed by PCR analysis. The effects of PC786 were largely unaffected by the multiplicity of infection (MOI) and were retained in the face of established RSV replication in a time-of-addition study. Persistent anti-RSV effects of PC786 were also demonstrated in human bronchial epithelial cells. In vivo intranasal once daily dosing with PC786 was able to reduce the virus load to undetectable levels in lung homogenates from RSV-infected mice and cotton rats. Treatment with escalating concentrations identified a dominant mutation in the L protein (Y1631H) in vitro. In addition, PC786 potently inhibited RSV RNA-dependent RNA polymerase (RdRp) activity in a cell-free enzyme assay and minigenome assay in HEp-2 cells (IC50, 2.1 and 0.5 nM, respectively). Thus, PC786 was shown to be a potent anti-RSV agent via inhibition of RdRp activity, making topical treatment with this compound a novel potential therapy for the treatment of human RSV infections. PMID:28652242

Continuous positive airway pressure with helmet versus mask in infants with bronchiolitis: an RCT.

PubMed

Chidini, Giovanna; Piastra, Marco; Marchesi, Tiziana; De Luca, Daniele; Napolitano, Luisa; Salvo, Ida; Wolfler, Andrea; Pelosi, Paolo; Damasco, Mirco; Conti, Giorgio; Calderini, Edoardo

2015-04-01

Noninvasive continuous positive airway pressure (CPAP) is usually applied with a nasal or facial mask to treat mild acute respiratory failure (ARF) in infants. A pediatric helmet has now been introduced in clinical practice to deliver CPAP. This study compared treatment failure rates during CPAP delivered by helmet or facial mask in infants with respiratory syncytial virus-induced ARF. In this multicenter randomized controlled trial, 30 infants with respiratory syncytial virus-induced ARF were randomized to receive CPAP by helmet (n = 17) or facial mask (n = 13). The primary endpoint was treatment failure rate (defined as due to intolerance or need for intubation). Secondary outcomes were CPAP application time, number of patients requiring sedation, and complications with each interface. Compared with the facial mask, CPAP by helmet had a lower treatment failure rate due to intolerance (3/17 [17%] vs 7/13 [54%], P = .009), and fewer infants required sedation (6/17 [35%] vs 13/13 [100%], P = .023); the intubation rates were similar. In successfully treated patients, CPAP resulted in better gas exchange and breathing pattern with both interfaces. No major complications due to the interfaces occurred, but CPAP by mask had higher rates of cutaneous sores and leaks. These findings confirm that CPAP delivered by helmet is better tolerated than CPAP delivered by facial mask and requires less sedation. In addition, it is safe to use and free from adverse events, even in a prolonged clinical setting. Copyright © 2015 by the American Academy of Pediatrics.

A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.

PubMed

Wang, Dai; Phan, Shannon; DiStefano, Daniel J; Citron, Michael P; Callahan, Cheryl L; Indrawati, Lani; Dubey, Sheri A; Heidecker, Gwendolyn J; Govindarajan, Dhanasekaran; Liang, Xiaoping; He, Biao; Espeseth, Amy S

2017-06-01

Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 10 3 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 10 6 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys

Bordetella pertussis is an uncommon pathogen in children hospitalized with bronchiolitis during the winter season.

PubMed

Piedra, Pedro A; Mansbach, Jonathan M; Jewell, Alan M; Thakar, Sneha D; Grant, Cameron C; Sullivan, Ashley F; Espinola, Janice A; Camargo, Carlos A

2015-06-01

In the United States (U.S.), Bordetella pertussis incidence has increased. Cough and apnea are common findings in pertussis and also in bronchiolitis, the most common cause of hospitalization in U.S. infants. The objective was to determine the prevalence of B. pertussis infection in children hospitalized with bronchiolitis and to describe its clinical course. Children hospitalized with bronchiolitis and age <2 years were eligible for a prospective, multicenter cohort study during 3 consecutive winter seasons (November-March) from 2007 to 2010. Sixteen sites in 12 states participated using a standardized enrollment protocol. Families were asked the 2010 Centers for Disease Control and Prevention pertussis classification questions. Nasopharyngeal aspirates were obtained and tested by real-time polymerase chain reaction for 16 viruses, Mycoplasma pneumoniae and B. pertussis. Two thousand sixty-eight (94%) of 2207 children had 1 or more respiratory pathogens. B. pertussis was identified in 4 children [0.2%; 95% confidence interval (CI): 0.1-0.5%] with 3 having a viral co-infection. All 4 were younger than 4 months; 2 met the Centers for Disease Control and Prevention definition of probable pertussis; and 3 had received at least 1 dose of an acellular pertussis vaccine. During the hospitalization, 2 had paroxysmal cough, 1 required intensive care unit care and the median length of stay was 13 days. Our data support that B. pertussis is an uncommon pathogen in U.S. children hospitalized with bronchiolitis in the winter. Making a diagnosis of pertussis can be challenging because the disease can be atypical and may not meet the Centers for Disease Control and Prevention definition of probable infection.

Infection with novel respiratory syncytial virus genotype Ontario (ON1) in adult hematopoietic cell transplant recipients, Texas, 2011-2013.

PubMed

Avadhanula, Vasanthi; Chemaly, Roy F; Shah, Dimpy P; Ghantoji, Shashank S; Azzi, Jacques M; Aideyan, Letisha O; Mei, Minghua; Piedra, Pedro A

2015-02-15

Respiratory syncytial virus (RSV) can cause severe respiratory disease in adult hematopoietic cell transplant (HCT) recipients. RSV subgroups A and B have evolved into multiple genotypes. We report on a recently described RSV genotype (ON1) in a cohort of adult HCT recipients in Texas. Twenty adult HCT recipients were enrolled as a part of an efficacy trial of ribavirin therapy. RSV identification and genotyping was performed using molecular techniques. RSV-specific neutralizing antibody (NAb) responses were measured. ON1 genotype was detected in 3 of 6 patients in the 2011-2012 season and in 8 of 14 patients in 2012-2013 season. Other genotypes detected were NA1 and BA. NAb levels were low at enrollment. Eight of 9 patients who cleared the RSV infection within 2 weeks mounted a ≥4-fold NAb response, compared with 2 of 8 who shed the virus for >2 weeks. The clinical course of those infected with ON1 was comparable to the course for individuals infected with other genotypes. This is the first report of RSV ON1 genotype in the United States, and ON1 genotype was dominant genotype in adult HCT recipients. Interestingly, faster viral clearance was associated with a ≥4-fold NAb response, likely indicating a reconstituted immune system. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Clinical and epidemiological differences between Bordetella pertussis and respiratory syncytial virus infections in infants: a matched case control study].

PubMed

Giménez-Sánchez, Francisco; Cobos-Carrascosa, Elena; Sánchez-Forte, Miguel; López-Sánchez, María Ángeles; González-Jiménez, Yolanda; Azor-Martínez, Ernestina

2014-01-01

An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

From the American Academy of Pediatrics: Policy statements--Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections.

PubMed

2009-12-01

Palivizumab was licensed in June 1998 by the US Food and Drug Administration for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients who are at increased risk of severe disease. Safety and efficacy have been established for infants born at or before 35 weeks' gestation with or without chronic lung disease of prematurity and for infants and children with hemodynamically significant heart disease. The American Academy of Pediatrics (AAP) published a policy statement on the use of palivizumab in November 1998 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1998;102[5]:1211-1216) and revised it in December 2003 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1442-1446), and an AAP technical report on palivizumab was published in 2003 (Meissner HC, Long SS; American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1447-1452). On the basis of the availability of additional data regarding seasonality of RSV disease as well as the limitations in available data on risk factors for identifying children who are at increased risk of serious RSV lower respiratory tract disease, AAP recommendations for immunoprophylaxis have been updated in an effort to ensure optimal balance of benefit and cost from this expensive intervention. This statement updates and replaces the 2003 AAP statement and the 2006 Red Book and is consistent with the 2009 Red Book recommendations.

Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal.

PubMed

Chu, Helen Y; Tielsch, James; Katz, Joanne; Magaret, Amalia S; Khatry, Subarna; LeClerq, Stephen C; Shrestha, Laxman; Kuypers, Jane; Steinhoff, Mark C; Englund, Janet A

2017-10-01

Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia in children. RSV-specific antibody (ab) protects infants from disease, and may be increased by a potential strategy of maternal RSV vaccination. To describe the effect of RSV antibody on RSV infection risk in infants in a resource-limited setting. In a prospective study in Nepal, women were enrolled during pregnancy and maternal and infant cord blood were collected at birth. Weekly surveillance for respiratory illness was performed from birth to 180days. Nasal swabs were tested for RSV by PCR and serum was tested using an RSV antibody microneutralization assay. Antibody concentrations at time of RSV infection were estimated based on a decay rate of 0.026 log 2 /day. Cord:maternal RSV antibody transfer ratio was 1.03 (0.88-1.19), with RSV antibody concentration of log 2 11.3 and log 2 11.7 in 310 paired maternal and infant samples, respectively. Cord blood RSV antibody was log 2 12.1 versus 11.6 in those with or without RSV infection (P=0.86). Among infants with RSV infection, estimated RSV antibody concentration at time of infection did not differ in infants with upper (n=8; log 2 10.7) versus lower respiratory tract infection (n=21; log 2 9.8; P=0.37). Cord blood RSV antibody concentrations did not correlate with age at primary RSV infection (R=0.11; P=0.57). Transplacental transfer of RSV antibody from mother to the fetus was highly efficient in mother-infant pairs in rural Nepal, though higher antibody concentrations were not protective against earlier or more severe RSV infection in infants. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

DIFFERENTIAL GENE EXPRESSION INDUCED BY RESPIRATORY SYNCTIAL VIRUS IN HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

Respiratory syncytial virus (RSV), a negative-stranded RNA virus, is a common viral pathogen for respiratory infection in both children and immunocompromised adults. Early host defense may play a critical role in determining the severity of the infection. To gain further insight ...

[Risk factors for acute respiratory syncytial virus infection of lower respiratory tract in hospitalized infants].

PubMed

Zhang, Xiaobo; Liu, Lijuan; Shi, Peng; Jiang, Gaoli; Jia, Pin; Wang, Chuankai; Wang, Libo; Qian, Liling

2014-05-01

To investigate the clinical epidemiologic characteristics and analyze risk factors for acute respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infection (ALRI). ALRI infants admitted to Children's Hospital of Fudan University from March 1st, 2011 to February 29th, 2012, were enrolled in this study. Patient information included demographic characteristics, feeding history, family status, clinical presentation, accessory examination, treatment and prognosis. According to the etiology of ALRI infants, we compared the seasonal distribution, demographic characteristics, household characteristics and underlying diseases between RSV-positive patients and RSV-negative patients. Univariate and multiple Logistic regression analyses were used to determine factors that were associated with risk of RSV infection. Among 1 726 ALRI infants, there were 913 RSV-positive infants (52.9%). The occurrence of RSV infection had a seasonal variation, with a peak in winter (59.1%). The median (P25, P75) age of RSV infants was 64 (21-155) days. The gestational age (GA) and body weight (BW) was (37.5 ± 2.4) weeks and (3.07 ± 0.66) kg, respectively. The male/female ratio among these was 1.9: 1. RSV infection was more popular among infants in the families with smoking members, crowded living conditions, history of atopic mother. Differences of the proportion of patients with underlying disease between RSV-positive and negative groups were statistically significant (59.4% vs. 54.2%, P < 0.05). Univariate logistic regression demonstrated that factors increasing the risk of RSV infection were: GA<37 weeks (OR = 1.346, 95%CI: 1.037-1.748), birth weight <2 500 g (OR = 1.447, 95%CI: 1.103-1.898), underlying diseases (OR = 1.232, 95%CI: 1.018-1.492), underlying CHD (OR = 1.391, 95%CI: 1.120-1.728), environmental tobacco smoke exposure (OR = 1.254, 95%CI: 1.035-1.519), mother with atopic diseases (OR = 1.827, 95%CI: 1.296-2.573), crowded house

Respiratory syncytial virus and influenza are the key viral pathogens in children <2 years hospitalized with bronchiolitis and pneumonia in Islamabad Pakistan.

PubMed

Bashir, Uzma; Nisar, Nadia; Arshad, Yasir; Alam, Muhammad Masroor; Ashraf, Asiya; Sadia, Hajra; Kazi, Birjees Mazher; Zaidi, Syed Sohail Zahoor

2017-03-01

Pneumonia remains a leading cause of morbidity and mortality in developing countries. Comprehensive surveillance data are needed to review the prevention and control strategies. We conducted active surveillance of acute lower respiratory infections among children aged <2 years hospitalized at two hospitals of Islamabad, Pakistan. Viral etiology was determined using real-time PCR on respiratory specimens collected during March 2011-April 2012. The overall mean age was 7.83 ± 5.25 months while no statistical difference between age or sex distribution of patients with positive and negative viral etiology (p > 0.05). The average weight of the study group was 6.1 ± 2.25 kg. ≥1 viral pathogens were detected in 75% cases. Major respiratory viruses included RSV-A: 44%, RSV-B: 23%, Influenza-A: 24.5%, Influenza-B: 7%, Adenovirus: 8.4% and HmPV: 5.2%. A single, dual or multiple viral pathogens were detected in 43%, 27% and 5.2% patients respectively. Common symptoms were cough (95%), apnoea (84%), fever (78%), wheeze (64.5%), nasal congestion (55%) and rhinorrhea (48%). Among the RSV positive cases, 2-6 months age group had highest detection rate for RSV-A (30%, n = 21/69) and RSV-B (20%, n = 14/69) while patients infected with Influenza-A were in 2.1-6 months age group (61%, 23/38). Statistically significant difference was observed between RSV-positive and negative cases for nutrition status (p = 0.001), cigarette/wood smoke exposure (p = 0.001) and concomitant clinical findings. Most patients had successful outcome on combination therapy with bronchodilators, inhaled steroids and antibiotics. Our findings underscore high burden of ALRI in Pakistan. Interventions targeting viral pathogens coupled with improved diagnostic approaches are critical for better prevention and control.

The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection

PubMed Central

Haynes, Lia M.; Anderson, Larry J.

2017-01-01

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting. PMID:28671606

The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection.

PubMed

Bakre, Abhijeet A; Harcourt, Jennifer L; Haynes, Lia M; Anderson, Larry J; Tripp, Ralph A

2017-07-03

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182-186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study.

PubMed

Wathuo, Miriam; Medley, Graham F; Nokes, D James; Munywoki, Patrick K

2016-12-14

Background A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the 'area under the curve' using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log 10 ribonucleic acid (RNA) copies. Young age (<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual's first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

Development of an Adenovirus-Based Respiratory Syncytial Virus Vaccine: Preclinical Evaluation of Efficacy, Immunogenicity, and Enhanced Disease in a Cotton Rat Model

PubMed Central

Kim, Eun; Okada, Kaori; Beeler, Judy A.; Crim, Roberta L.; Piedra, Pedro A.; Gilbert, Brian E.

2014-01-01

ABSTRACT The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5.RSV-F) and the protection provided following immunization with Ad5.RSV-F and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given i.m. or i.n., and these responses correlated with reduced replication of the virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5.RSV-F at 1 × 1011 viral particles (v.p.) elicited antibody titers 64- to 256-fold greater than those seen after natural infection. CRs boosted with Ad5.RSV-F i.n. 28 days after an i.m. dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F-protein antigenic sites revealed substantial differences between antibodies elicited by Ad5.RSV-F and those seen after RSV infection; differences in antibody profiles were also seen between CRs given Ad5.RSV-F i.m. and CRs given Ad5.RSV-F i.n. Ad5.RSV-F priming did not result in enhanced disease following live-virus challenge, in contrast to the histopathology seen in CRs given the formalin-inactivated RSV/A/Burnett vaccine. IMPORTANCE Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in infants and young children and a serious health threat in the immunocompromised and the elderly. Infection severity increased in children in an immunization trial, hampering the over 4-decade-long quest for a successful RSV vaccine. In this study, we show that a genetically engineered RSV-F-encoding adenoviral vector provides protective

International Variation in Asthma and Bronchiolitis Guidelines.

PubMed

Bakel, Leigh Anne; Hamid, Jemila; Ewusie, Joycelyne; Liu, Kai; Mussa, Joseph; Straus, Sharon; Parkin, Patricia; Cohen, Eyal

2017-11-01

Guideline recommendations for the same clinical condition may vary. The purpose of this study was to determine the degree of agreement among comparable asthma and bronchiolitis treatment recommendations from guidelines. National and international guidelines were searched by using guideline databases (eg, National Guidelines Clearinghouse: December 16-17, 2014, and January 9, 2015). Guideline recommendations were categorized as (1) recommend, (2) optionally recommend, (3) abstain from recommending, (4) recommend against a treatment, and (5) not addressed by the guideline. The degree of agreement between recommendations was evaluated by using an unweighted and weighted κ score. Pairwise comparisons of the guidelines were evaluated similarly. There were 7 guidelines for asthma and 4 guidelines for bronchiolitis. For asthma, there were 166 recommendation topics, with 69 recommendation topics given in ≥2 guidelines. For bronchiolitis, there were 46 recommendation topics, with 21 recommendation topics provided in ≥2 guidelines. The overall κ for asthma was 0.03, both unweighted (95% confidence interval [CI]: -0.01 to 0.07) and weighted (95% CI: -0.01 to 0.10); for bronchiolitis, it was 0.32 unweighted (95% CI: 0.16 to 0.52) and 0.15 weighted (95% CI: -0.01 to 0.5). Less agreement was found in national and international guidelines for asthma than for bronchiolitis. Additional studies are needed to determine if differences are based on patient preferences and values and economic considerations or if other recommendation-level, guideline-level, and condition-level factors are driving these differences. Copyright © 2017 by the American Academy of Pediatrics.

Decrease in Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) Enhanced Disease with RSV G Glycoprotein Peptide Immunization in BALB/c Mice

PubMed Central

Rey, Gertrud U.; Miao, Congrong; Caidi, Hayat; Trivedi, Suvang U.; Harcourt, Jennifer L.; Tripp, Ralph A.; Anderson, Larry J.; Haynes, Lia M.

2013-01-01

Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study. PMID:24376637

Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soukup, J.; Koren, H.S.; Becker, S.

1993-01-01

The study was performed to evaluate the effect of ozone (O3) exposure at 1 ppm for 2 hr on the susceptibility/resistance of adult human alveolar macrophages (AM) to infection with respiratory syncytial virus (RSV) in vitro and on RSV-induced cytokine production by the AM. AM were first exposed to O3 or to filtered air and then infected with RSV at multiplicities of infection (m.o.i.) of 0.1 1.0 and 10. The percentage RSV-infected AM and the amount of infectious virus released by the cells were determined at Days 2 and 4 after infection. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)more » levels in the supernatants were determined on Day 2. No difference in the percentage infected AM or in the amount of infectious RSV produced was found between control and O3-exposed cultures. However, O3-exposed AM infected with RSV at m.o.i. 1 produced less IL-1 in response to RSV infection than control AM:63.6 pg/ml compared with 98.5 pg/ml. No difference in IL-1 was seen with m.o.i. 10. IL-6 levels were also decreased, but only after infection with m.o.i. 0.1. At this level of infection 830 pg/ml was produced by control AM as compared to 468.2 pg/ml by O3-exposed AM. TNF production was unaffected by O3 at all multiplicities of infection. (Copyright (c) 1993 by Academic Press, Inc.)« less

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children.

PubMed

Okiro, Emelda A; White, Lisa J; Ngama, Mwanajuma; Cane, Patricia A; Medley, Graham F; Nokes, D James

2010-01-22

Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community.

Management of acute bronchiolitis in emergency wards in Spain: variability and appropriateness analysis (aBREVIADo Project).

PubMed

Ochoa Sangrador, Carlos; González de Dios, Javier

2012-07-01

Most patients with acute bronchiolitis have a mild course and only require outpatient care. However, some of them have to go to emergency departments, because they have respiratory distress or feeding problems. There, they frequently receive diagnostic and therapeutic procedures. We want to know the variability and appropriateness of these procedures. A cross-sectional study (October 2007 to March 2008) was carried out on 2,430 diagnosed cases of bronchiolitis in hospital emergency departments, which required no hospitalization. An analysis of the appropriateness of the treatments was made in 2,032 cases gathered in ten departments with at least 100 cases, using as criterion the recommendations of a consensus conference. We estimated the adjusted percentages of each department. Most of the bronchiolitis were mild, in spite that they underwent multiple diagnostic and therapeutic procedures. In the acute phase, different treatments were used: inhaled beta 2 agonists (61.4%), antipyretics (17.1%), oral steroids (11.3%), and nebulized adrenaline (9.3%). In the maintenance phase, the most common treatments were: inhaled beta 2 agonists (50.5%), oral steroids (17%), oral beta 2 agonists (14.9%), and antibiotics (6.1%). The 64% of the treatments used in the acute phase and the 55.9% in the maintenance phase were considered inappropriate in the appropriateness analysis; a great heterogeneity among centers was found. There are discrepancies between clinical practice and evidence-based management of bronchiolitis in Spanish emergency departments. Inappropriate treatments were used in more than half of patients. The wide variation between centers shows the influence of local prescribing habits and reveals the scope for improvement.

Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

PubMed

Galván, José María; Rajas, Olga; Aspa, Javier

2015-11-01

Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Natural History of Human Respiratory Syncytial Virus Inferred from Phylogenetic Analysis of the Attachment (G) Glycoprotein with a 60-Nucleotide Duplication

PubMed Central

Trento, Alfonsina; Viegas, Mariana; Galiano, Mónica; Videla, Cristina; Carballal, Guadalupe; Mistchenko, Alicia S.; Melero, José A.

2006-01-01

A total of 47 clinical samples were identified during an active surveillance program of respiratory infections in Buenos Aires (BA) (1999 to 2004) that contained sequences of human respiratory syncytial virus (HRSV) with a 60-nucleotide duplication in the attachment (G) protein gene. This duplication was analogous to that previously described for other three viruses also isolated in Buenos Aires in 1999 (A. Trento et al., J. Gen. Virol. 84:3115-3120, 2003). Phylogenetic analysis indicated that BA sequences with that duplication shared a common ancestor (dated about 1998) with other HRSV G sequences reported worldwide after 1999. The duplicated nucleotide sequence was an exact copy of the preceding 60 nucleotides in early viruses, but both copies of the duplicated segment accumulated nucleotide substitutions in more recent viruses at a rate apparently higher than in other regions of the G protein gene. The evolution of the viruses with the duplicated G segment apparently followed the overall evolutionary pattern previously described for HRSV, and this genotype has replaced other prevailing antigenic group B genotypes in Buenos Aires and other places. Thus, the duplicated segment represents a natural tag that can be used to track the dissemination and evolution of HRSV in an unprecedented setting. We have taken advantage of this situation to reexamine the molecular epidemiology of HRSV and to explore the natural history of this important human pathogen. PMID:16378999

Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and conventional dairy herds.

PubMed

Wolff, Cecilia; Emanuelson, Ulf; Ohlson, Anna; Alenius, Stefan; Fall, Nils

2015-01-13

Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. It has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. Organically managed (OM) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (CM) herds. The objective of this study was to challenge the hypothesis of a lower occurrence of BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and May 2013 milk samples from four homebred primiparous cows were collected in 75 to 65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was analysed with commercial indirect ELISAs. Herds were classified as positive if at least one individual sample was positive. The prevalence of positive herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among OM and CM herds, over the three sampling occasions. There was no statistically significant difference between OM and CM herds at any sampling occasion. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The incidence of herds turning sero-negative between samplings corresponded to the incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in the herds and analysed. Several herds were negative on individual samples but positive in BTM. Herd-level data on production, health and reproduction were retrieved from VÄXA Sweden and the study herds were representative of the source population. There was no difference in prevalence of or incidence risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of herds becoming seropositive was balanced by herds becoming seronegative it should be possible to lower the prevalence of these two

Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection

PubMed Central

Mejias, Asuncion; Dimo, Blerta; Suarez, Nicolas M.; Garcia, Carla; Suarez-Arrabal, M. Carmen; Jartti, Tuomas; Blankenship, Derek; Jordan-Villegas, Alejandro; Ardura, Monica I.; Xu, Zhaohui; Banchereau, Jacques; Chaussabel, Damien; Ramilo, Octavio

2013-01-01

Background Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. Methods and Findings This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%–98%]) and specificity (98% [95% CI 88%–99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. Conclusions Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for

Formation of a stable mimic of ambient particulate matter containing viable infectious respiratory syncytial virus and its dry-deposition directly onto cell cultures.

PubMed

Cruz-Sanchez, Teresita M; Haddrell, Allen E; Hackett, Tillie L; Singhera, Gurpreet K; Marchant, David; Lekivetz, Ryan; Meredith, Anna; Horne, Derrick; Knight, Darryl A; van Eeden, Stephen F; Bai, Tony R; Hegele, Richard G; Dorscheid, Delbert R; Agnes, George R

2013-01-15

Epidemiological associations of worse respiratory outcomes from combined exposure to ambient particulate matter (PM) and respiratory viral infection suggest possible interactions between PM and viruses. To characterize outcomes of such exposures, we developed an in vitro mimic of the in vivo event of exposure to PM contaminated with respiratory syncytial virus (RSV). Concentration of infectious RSV stocks and a particle levitation apparatus were the foundations of the methodology developed to generate specific numbers of PM mimics (PM(Mimics)) of known composition for dry, direct deposition onto airway epithelial cell cultures. Three types of PM(Mimics) were generated for this study: (i) carbon alone (P(C)), (ii) carbon and infectious RSV (P(C+RSV)), and (iii) aerosols consisting of RSV (A(RSV)). P(C+RSV) were stable in solution and harbored infectious RSV for up to 6 months. Unlike A(RSV) infection, P(C+RSV) infection was found to be dynamin dependent and to cause lysosomal rupture. Cells dosed with PM(Mimics) comprised of RSV (A(RSV)), carbon (P(C)), or RSV and carbon (P(C+RSV)) responded differentially as exemplified by the secretion patterns of IL-6 and IL-8. Upon infection, and prior to lung cell death due to viral infection, regression analysis of these two mediators in response to incubation with A(RSV), P(C), or P(C+RSV) yielded higher concentrations upon infection with the latter and at earlier time points than the other PM(Mimics). In conclusion, this experimental platform provides an approach to study the combined effects of PM-viral interactions and airway epithelial exposures in the pathogenesis of respiratory diseases involving inhalation of environmental agents.

Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line

PubMed Central

Sarmiento, Rosa E; Tirado, Rocio G; Valverde, Laura E; Gómez-Garcia, Beatriz

2007-01-01

Background The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV) antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2) were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs) and intracellular viral proteins were detected by indirect immunoflourescence. Results Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death. Conclusion The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell. PMID:17608950

T cell source of type 1 cytokines determines illness patterns in respiratory syncytial virus-infected mice.

PubMed Central

Tang, Y. W.; Graham, B. S.

1997-01-01

Manipulation of the cytokine microenvironment at the time of vaccination can influence immune responses to remote challenge, providing a strategy to study the molecular pathogenesis of respiratory syncytial virus (RSV) vaccine-enhanced disease in the mouse model. Although treatment with antibody against IL-4 or recombinant IL-12 (rIL-12) at the time of formalin-inactivated RSV vaccination induced a similar shift in the pattern of cytokine mRNA expression upon live virus challenge, anti-IL-4 treated mice had increased CD8+ cytotoxic T lymphocyte activity and reduced illness compared with rIL-12-treated mice. To define effector mechanisms responsible for these patterns, CD4+ and/or CD8+ T lymphocytes were selectively depleted in vivo at the time of RSV challenge. In rIL-12-treated mice, CD4+ lymphocytes made the largest contribution to IFN-gamma mRNA, RSV clearance, and illness, while in anti-IL-4 treated mice, CD8+ lymphocytes were the major effector. The effector responsible for virus clearance also mediated illness, suggesting that efficiency of virus clearance determined disease expression. These results demonstrate that the phenotype of effector cells involved in the immune response to virus challenge may be a more important determinant of disease than patterns of cytokine expression classically assigned to Th1 and Th2 lymphocytes. PMID:9151790

Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells

PubMed Central

Kim, Ki-Hye; Lee, Young-Tae; Hwang, Hye Suk; Kwon, Young-Man; Jung, Yu-Jin; Lee, Youri; Lee, Jong Seok; Lee, Yu-Na; Park, Soojin; Kang, Sang-Moo

2015-01-01

Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FI-RSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine-enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease. PMID:26468884

Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region.

PubMed

Mlinaric-Galinovic, Gordana; Tabain, Irena; Kukovec, Tamara; Vojnovic, Gordana; Bozikov, Jadranka; Bogovic-Cepin, Jasna; Ivkovic-Jurekovic, Irena; Knezovic, Ivica; Tesovic, Goran; Welliver, Robert C

2012-06-01

The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction. Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Correlation of cytotoxic activity in lungs to recovery of normal and gamma-irradiated cotton rats from respiratory syncytial virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, C.S.; Wyde, P.R.; Knight, V.

1983-10-01

Cotton rats (Sigmodon hispidus) that were exposed to 300, 600, or 900 rads of gamma irradiation and inoculated intranasally 2 days later with respiratory syncytial virus (RSV) exhibited prolonged virus shedding and delayed humoral and cytotoxic immune responses compared with comparably inoculated nonirradiated control rats. In nonirradiated animals and in animals exposed to 300 and 600 rads, levels of virus declined and then disappeared from the lungs during the period in which cytotoxic activity was maximal in the lungs of these animals. In contrast, in the group of cotton rats exposed to 900 rads of irradiation, local cytotoxic activity remainedmore » low throughout the 11-day observation period, and virus was not eliminated from the lungs. Although virus-neutralizing antibodies in serum and lavage fluids from these animals may have been involved, correlation of antibody concentrations with virus clearance from lungs was not as evident. These data suggest that cytotoxic effector cells have a positive role in eliminating RSV from the lungs of unprimed cotton rats.« less

IL-17 Plays a Role in Respiratory Syncytial Virus-induced Lung Inflammation and Emphysema in Elastase and LPS-injured Mice.

PubMed

Mebratu, Yohannes A; Tesfaigzi, Yohannes

2018-06-01

Respiratory syncytial virus (RSV) is associated with enhanced progression of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. However, little is known about the role of IL-17 in RSV-induced lung injury. We first investigated the role of RSV infection in enhancing mucous cell hyperplasia (MCH) and airspace enlargement in the lungs of mice injured with elastase and LPS (E/LPS). Mice injured with E/LPS had an enhanced and prolonged neutrophilic response to RSV that was associated with decreased levels of type I IFN and increased levels of IL-17, IL-23, CXCL-1, granulocyte colony stimulating factor (GCSF), CXCL-5, and matrix metalloproteinase (MMP)-9. In addition, extent of MCH and mean weighted alveolar space were increased significantly in the lungs of E/LPS-injured mice infected with RSV compared with E/LPS-only or RSV-only controls. Interestingly, immunodepletion of IL-17 before viral infection diminished the RSV-driven MCH and airspace enlargement in the E/LPS-injured animals, suggesting that IL-17 may be a therapeutic target for MCH and airspace enlargement when enhanced by RSV infection.

Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness.

PubMed

Miller, E Kathryn; Williams, John V; Gebretsadik, Tebeb; Carroll, Kecia N; Dupont, William D; Mohamed, Yassir A; Morin, Laura-Lee; Heil, Luke; Minton, Patricia A; Woodward, Kimberly; Liu, Zhouwen; Hartert, Tina V

2011-04-01

Risk factors for severe human rhinovirus (HRV)-associated infant illness are unknown. We sought to examine the role of HRV infection in infant respiratory tract illness and assess viral and host risk factors for HRV-associated disease severity. We used a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory tract illness during the fall-spring months of 2004-2008. Illness severity was determined by using an ordinal bronchiolitis severity score, with higher scores indicating more severe disease. HRV was identified by means of real-time RT-PCR. The VP4/VP2 region from HRV-positive specimens was sequenced to determine species. Of 630 infants with bronchiolitis or upper respiratory tract illnesses (URIs), 162 (26%) had HRV infection; HRV infection was associated with 18% of cases of bronchiolitis and 47% of cases of URI. Among infants with HRV infection, 104 (64%) had HRV infection alone. Host factors associated with more severe HRV-associated illness included a maternal and family history of atopy (median score of 3.5 [interquartile range [IQR], 1.0-7.8] vs 2.0 [IQR, 1.0-5.2] and 3.5 [IQR, 1.0-7.5] vs 2.0 [IQR, 0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in the risk for more severe HRV-associated bronchiolitis (odds ratio, 2.39; 95% CI, 1.14-4.99; P = .02). In a similar model maternal asthma was also associated with greater HRV-associated bronchiolitis severity (odds ratio, 2.49, 95% CI, 1.10-5.67; P = .03). Among patients with HRV infection, 35% had HRVA, 6% had HRVB, and 30% had HRVC. HRV infection was a frequent cause of bronchiolitis and URIs among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial viral genetic diversity was seen among the patients with HRV infection, and predominant groups varied by season and year. Host factors, including maternal atopy, were associated with more severe

Comparison of Initial Response of Nebulized Salbutamol and Adrenaline in Infants and young Children Admitted with Acute Bronchiolitis.

PubMed

Adhikari, S; Thapa, P; Rao, K S; Bk, G

2016-01-01

Background Acute bronchiolitis is common cause of hospitalization in infants and young children. There are widespread variations in the diagnosis and management. Despite the use of bronchodilators for decades, there is lack of consensus for the benefit of one above another. Objective To compare initial response of nebulized adrenaline and salbutamol. Method Children aged two months to two years admitted with acute bronchiolitis in the department of Paediatrics of Manipal teaching hospital, Pokhara, Nepal, from 1st March 2014 to 28th February 2015 were enrolled. Patients fulfilling inclusion criteria received either adrenaline or salbutamol nebulization. Data were collected in a predesigned proforma. Respiratory distress assessment instrument (RDAI) scores were considered primary outcome measure and respiratory rate at 48 hours, duration of hospital stay, requirement of supplemental oxygen and intravenous fluid were considered secondary outcome measure. Result A total of 40 patients were enrolled in each study group. Mean RDAI scores at admission was in 9.75 with (CI- 9.01, 10.49) in adrenaline and 9.77 (CI- 9.05, 10.50) in salbutamol group. There was gradual decline in mean RDAI scores in both the groups over 48 hours to 4.15 (CI- 3.57,4.73) and 4.13 (CI- 3.69,4.56) in adrenaline and salbutamol group respectively. Hospital stay was 5.32 days in adrenaline and 5.68 days in salbutamol group. Patients nebulized with adrenaline required oxygen for 33.30 hours compared with 36.45 hours in salbutamol. Intravenous fluid duration was also less in adrenaline group compared to salbutamol group (33.15 vs 37.80 hours). Conclusion Patients of acute bronchiolitis nebulized with either salbutamol or adrenaline experienced similar decline in RDAI scores in the first 48 hours. Duration of supplementary oxygen and intravenous fluid was less in adrenaline group compared with salbutamol group.

When to perform urine cultures in respiratory syncytial virus-positive febrile older infants?

PubMed

Kaluarachchi, Dinushan; Kaldas, Virginia; Erickson, Evelyn; Nunez, Randolph; Mendez, Magda

2014-09-01

Respiratory syncytial virus (RSV) infections are associated with clinically significant rate of urinary tract infections (UTIs) in young infants. Previous research investigating RSV infections and UTIs has been performed mainly in infants younger than 2 to 3 months and has not focused on the risk of UTI in infants 3 to 12 months. This study aimed to assess the rate of UTIs in febrile RSV-positive older infants admitted as inpatients and identify predictors of UTI in febrile RSV-positive older infants. This is a retrospective comparative study of febrile RSV-positive infants 0 to 12 months of age admitted to the inpatient pediatric unit of Lincoln Medical and Mental Health Center, Bronx, from September through April 2006 to 2012. Infants 3 to 12 months were considered the cases, and infants 0 to 3 months were the comparative group. The rate of UTIs between the 2 groups was compared. Univariate tests and multiple logistic regression were used to identify demographic/clinical factors associated with UTI in febrile RSV-positive older infants. A total of 414 RSV-positive febrile infants were enrolled including 297 infants 3 to 12 months of age. The rate of UTI in older infants was 6.1% compared with 6.8% in infants younger than 3 months. Positive urinalysis finding was an independent predictor of UTI (P = 0.003) in older infants. All 11 boys with UTI were uncircumcised, and none of the 51 circumcised boys had UTI. Demographic (race, sex, and age) and clinical factors (temperature, white blood cell count, and absolute neutrophil count) were not associated with UTI. Febrile older infants who are RSV positive have a clinically significant rate of UTIs. It seems prudent to examine the urine of these older infants. Positive urinalysis finding was a predictive factor of UTI. Circumcised boys are at a decreased risk of UTI, compared with uncircumcised boys.

Differential antiviral activities of respiratory syncytial virus (RSV) inhibitors in human airway epithelium.

PubMed

Mirabelli, Carmen; Jaspers, Martine; Boon, Mieke; Jorissen, Mark; Koukni, Mohamed; Bardiot, Dorothée; Chaltin, Patrick; Marchand, Arnaud; Neyts, Johan; Jochmans, Dirk

2018-03-27

We report the use of reconstituted 3D human airway epithelium cells (HuAECs) of bronchial origin in an air-liquid interface to study respiratory syncytial virus (RSV) infection and to assess the efficacy of RSV inhibitors in (pre-)clinical development. HuAECs were infected with RSV-A Long strain (0.01 CCID50/cell, where CCID50 represents 50% cell culture infectious dose in HEp2 cells) on the apical compartment of the culture. At the time of infection or at 1 or 3 days post-infection, selected inhibitors were added and refreshed daily on the basal compartment of the culture. Viral shedding was followed up by apical washes collected daily and quantifying viral RNA by RT-qPCR. RSV-A replicates efficiently in HuAECs and viral RNA is shed for weeks after infection. RSV infection reduces the ciliary beat frequency of the ciliated cells as of 4 days post-infection, with complete ciliary dyskinesia observed by day 10. Treatment with RSV fusion inhibitors resulted in an antiviral effect only when added at the time of infection. In contrast, the use of replication inhibitors (both nucleoside and non-nucleoside) elicited a marked antiviral effect even when the start of treatment was delayed until 1 day or even 3 days after infection. Levels of the inflammation marker RANTES (mRNA) increased ∼200-fold in infected, untreated cultures (at 3 weeks post-infection), but levels were comparable to those of uninfected cultures in the presence of PC786, an RSV replication inhibitor, suggesting that an efficient antiviral treatment might inhibit virus-induced inflammation in this model. Overall, HuAECs offer a robust and physiologically relevant model to study RSV replication and to assess the efficacy of antiviral compounds.

Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection

PubMed Central

Sampayo-Escobar, Viviana; Green, Ryan; Cheung, Michael B.; Bedi, Raminder; Mohapatra, Subhra

2018-01-01

The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling may play a pivotal role in the spread of RSV infection. PMID:29677209

Ocular Tropism of Respiratory Viruses

PubMed Central

Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

Respiratory Morbidity in a Coffee Processing Workplace With Sentinel Obliterative Bronchiolitis Cases

PubMed Central

Bailey, Rachel L.; Cox-Ganser, Jean M.; Duling, Matthew G.; LeBouf, Ryan F.; Martin, Stephen B.; Bledsoe, Toni A.; Green, Brett J.; Kreiss, Kathleen

2016-01-01

Rationale Obliterative bronchiolitis in former coffee workers prompted a cross-sectional study of current workers. Diacetyl and 2,3-pentanedione levels were highest in areas for flavoring and grinding/packaging unflavored coffee. Methods We interviewed 75 (88%) workers, measured lung function, and created exposure groups based on work history. We calculated standardized morbidity ratios (SMRs) for symptoms and spirometric abnormalities. We examined health outcomes by exposure groups. Results SMRs were elevated 1.6-fold for dyspnea and 2.7-fold for obstruction. The exposure group working in both coffee flavoring and grinding/packaging of unflavored coffee areas had significantly lower mean ratio of forced expiratory volume in 1 s to forced vital capacity and percent predicted mid-expiratory flow than workers without such exposure. Conclusion Current workers have occupational lung morbidity associated with high diacetyl and 2,3-pentanedione exposures, which were not limited to flavoring areas. PMID:26523478

Nasogastric hydration versus intravenous hydration for infants with bronchiolitis: a randomised trial.

PubMed

Oakley, Ed; Borland, Meredith; Neutze, Jocelyn; Acworth, Jason; Krieser, David; Dalziel, Stuart; Davidson, Andrew; Donath, Susan; Jachno, Kim; South, Mike; Theophilos, Theane; Babl, Franz E

2013-04-01

Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospital admission. Hydration is a mainstay of treatment, but insufficient evidence exists to guide clinical practice. We aimed to assess whether intravenous hydration or nasogastric hydration is better for treatment of infants. In this multicentre, open, randomised trial, we enrolled infants aged 2-12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons (April 1-Oct 31, in 2009, 2010, and 2011). We randomly allocated infants to nasogastric hydration or intravenous hydration by use of a computer-generated sequence and opaque sealed envelopes, with three randomly assigned block sizes and stratified by hospital site and age group (2-<6 months vs 6-12 months). The primary outcome was length of hospital stay, assessed in all randomly assigned infants. Secondary outcomes included rates of intensive-care unit admission, adverse events, and success of insertion. This trial is registered with the Australian and New Zealand clinical trials registry, ACTRN12605000033640. Mean length of stay for 381 infants assigned nasogastric hydration was 86·6 h (SD 58·9) compared with 82·2 h (58·8) for 378 infants assigned intravenous hydration (absolute difference 4·5 h [95% CI -3·9 to 12·9]; p=0·30). Rates of admission to intensive-care units, need for ventilatory support, and adverse events did not differ between groups. At randomisation, seven infants assigned nasogastric hydration were switched to intravenous hydration and 56 infants assigned intravenous hydration were switched to nasogastric hydration because the study-assigned method was unable to be inserted. For those infants who had data available for successful insertion, 275 (85%) of 323 infants in the nasogastric hydration group and 165 (56%) of 294 infants in the intravenous hydration group required only one attempt for successful

Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series.

PubMed

Egilman, David S; Schilling, John Henry

2012-01-01

Respiratory exposure to diacetyl and diacetyl-containing flavorings used in butter-flavored microwave popcorn (BFMP) causes lung disease, including bronchiolitis obliterans (BO), in flavorings and popcorn manufacturing workers. However, there are no published reports of lung disease among BFMP consumers. We present a case series of three BFMP consumers with biopsy-confirmed BO. We review data relating to consumer exposures, estimate case exposures, and compare them to diacetyl-containing flavoring-exposed manufacturing workers with lung disease. These consumer cases' exposure levels are comparable to those that caused disease in workers. We were unable to identify any other exposures or diseases known or suspected to cause BO in these cases. BFMP poses a significant respiratory risk to consumers. Some manufacturers have substituted diacetyl with other alpha-diketones that are likely to pose a similar risk. Simple consumer practices such as cooling the popcorn bag would eliminate the risk of severe lung disease.

Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

PubMed Central

Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

2013-01-01

Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactiva ted virus.

PubMed Central

Prince, G A; Jenson, A B; Hemming, V G; Murphy, B R; Walsh, E E; Horswood, R L; Chanock, R M

1986-01-01

Cotton rats previously inoculated with Formalin-inactivated respiratory syncytial virus (RSV) were challenged intranasally with live RSV to induce an enhancement of RSV disease similar to that observed after the administration of Formalin-inactivated RSV vaccine to human infants 20 years ago. Within 24 h after infection with RSV, cotton rats developed pulmonary lesions that reached a maximum by day 4. Histologically, the lesions resembled an experimental pulmonary Arthus reaction. An action of Formalin on RSV appears to be responsible for this effect, because live virus or virus heated in the absence of Formalin did not induce enhanced immunopathology. Selected epitopes on the fusion (F) or attachment (G) or both RSV surface glycoproteins that are involved in inducing neutralizing antibodies were modified to reduce or ablate their antigenicity. However, other epitopes on the F or G or both glycoproteins were not ablated by Formalin, because cotton rats inoculated parenterally with a Formalin-inactivated virus developed a high level of F and G antibodies measurable by an enzyme-linked immunosorbent assay. At this time, the effect of Formalin on RSV cannot be localized to either the F or G glycoprotein of RSV. Images PMID:2419587

Serum antibody response to respiratory syncytial virus F and N proteins in two populations at high risk of infection: children and elderly.

PubMed

Sastre, P; Cusi, M G; Manoha, C; Schildgen, O; Ruiz, T; Vela, C; Rueda, P

2010-09-01

Human respiratory syncytial virus (hRSV) is the main viral cause of severe respiratory infections in children and a common cause of morbidity in the elderly. The nucleocapsid (N) and fusion (F) proteins of hRSV were expressed in insect cells and used as antigens in two independent enzyme-linked immunosorbent assays (ELISAs) to measure the serum antibody response in two populations at high risk of hRSV infection, children and the elderly. Fifty-seven serum specimens from children aged from 1 to 10 years old and 91 sera from adults over 60 years old were tested. The ELISA results were compared with those obtained by an immunofluorescence assay (IFA) based on hRSV-infected cells, which was considered as the reference technique. Sensitivity and specificity were 94% and 85% for the N-ELISA and 86% and 81% for the F-ELISA, respectively. When the immune responses of the two groups of individuals were compared, it appeared that almost 100% of the elderly had antibodies against the N or F protein whereas only 50% of the sera from children had antibodies against either of the two viral proteins. In conclusion, the F and N ELISAs can be used successfully for detecting a specific antibody response to hRSV. Copyright 2010 Elsevier B.V. All rights reserved.

Effect of climate on incidence of respiratory syncytial virus infections in a refugee camp in Kenya: A non-Gaussian time-series analysis

PubMed Central

Omony, Jimmy; Mwalili, Samuel M.; Achia, Thomas N. O.; Gichangi, Anthony; Mwambi, Henry

2017-01-01

Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) in children. Children younger than 1 year are the most susceptible to RSV infection. RSV infections occur seasonally in temperate climate regions. Based on RSV surveillance and climatic data, we developed statistical models that were assessed and compared to predict the relationship between weather and RSV incidence among refugee children younger than 5 years in Dadaab refugee camp in Kenya. Most time-series analyses rely on the assumption of Gaussian-distributed data. However, surveillance data often do not have a Gaussian distribution. We used a generalized linear model (GLM) with a sinusoidal component over time to account for seasonal variation and extended it to a generalized additive model (GAM) with smoothing cubic splines. Climatic factors were included as covariates in the models before and after timescale decompositions, and the results were compared. Models with decomposed covariates fit RSV incidence data better than those without. The Poisson GAM with decomposed covariates of climatic factors fit the data well and had a higher explanatory and predictive power than GLM. The best model predicted the relationship between atmospheric conditions and RSV infection incidence among children younger than 5 years. This knowledge helps public health officials to prepare for, and respond more effectively to increasing RSV incidence in low-resource regions or communities. PMID:28570627

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

PubMed Central

2010-01-01

Background Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community. PMID:20096106

ROLE OF MONOCYTES IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION.

EPA Science Inventory

ROLE OF MONOCYTES IN RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION.
Joleen M. Soukup and Susanne Becker, National Health and Environmental Effects Research
Laboratory, US EPA, Research Traingle Park, NC USA.

RSV infection in airway epithelial cells (EC) results i...

Outcomes of Patients with Respiratory Distress Treated with Bubble CPAP on a Pediatric Ward in Malawi.

PubMed

Machen, Heather E; Mwanza, Zondiwe V; Brown, Jocelyn K; Kawaza, Kondwani M; Newberry, Laura; Richards-Kortum, Rebecca R; Oden, Z Maria; Molyneux, Elizabeth M

2015-12-01

To describe the outcomes of infants and young children with respiratory distress when treated with a novel, low-cost, stand-alone bubble Continuous Positive Airway Pressure (bCPAP) system in a resource-limited setting. A non-randomized, convenience sample study in a pediatric unit in Blantyre, Malawi, 2013. Patients weighing ≤10 kg with respiratory distress were eligible. We compared outcomes for patients with bronchiolitis, pneumonia and Pneumocystis jiroveci pneumonia (PJP) after treatment with bCPAP. Seventy percent of patients treated with bCPAP survived. Outcomes were best for patients with bronchiolitis and worst for those with PJP. Most survivors (80%) showed improvement within 24 h. All treating physicians found bCPAP useful, leading to a change in practice. Bubble CPAP was most beneficial to patients with bronchiolitis. Children, who were going to get well, tended to get well quickly. Physicians believed the bCPAP system provided a higher level of care than nasal oxygen. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

PubMed Central

Mukhopadhyay, Indranil; Kulkarni, Abhay; Khairatkar-Joshi, Neelima

2016-01-01

Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. PMID:27827953

Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs.

PubMed

Garg, R; Latimer, L; Wang, Y; Simko, E; Gerdts, V; Potter, A; van Drunen Littel-van den Hurk, S

2016-01-04

Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung

PubMed Central

Numata, Mari; Grinkova, Yelena V; Mitchell, James R; Chu, Hong Wei; Sligar, Stephen G; Voelker, Dennis R

2013-01-01

There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 μg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a halftime of 60–120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo. PMID:23717040

Human respiratory syncytial virus: prevalence, viral co-infections and risk factors for lower respiratory tract infections in children under 5 years of age at a general hospital in the Democratic Republic of Congo.

PubMed

Kabego, Landry; Balol'Ebwami, Serge; Kasengi, Joe Bwija; Miyanga, Serge; Bahati, Yvette Lufungulo; Kambale, Richard; de Beer, Corena

2018-04-01

This study aimed to determine the prevalence of human respiratory syncytial virus (HRSV) acute respiratory infection (ARI) in children under the age of 5 years at the Provincial General Hospital of Bukavu (PGHB), and to analyse factors associated with the risk of ARI being diagnosed as lower respiratory tract infection (LRTI). A total of 146 children under 5 years visiting the PGHB for ARI between August and December 2016 were recruited, and socio-demographic information, clinical data and nasopharyngeal swabs were collected. The samples were analysed by a multiplex reverse transcriptase polymerase chain reaction targeting 15 different viruses. Of 146 samples collected, 84 (57.5 %) displayed a positive result of at least one of the 15 viruses. The overall prevalence of HRSV was 21.2 %. HRSV A (30, 20.5 %) was the virus the most detected, followed by HRV (24, 16.4 %), PIV3 (20, 16.6) and ADV (7, 4.79 %). The other viruses were detected in three or fewer cases. There were only 11 (7.5 %) cases of co-infection. HRSV infection, malnutrition, younger age, rural settings, low income and mother illiteracy were associated with the risk of ARI being diagnosed as LRTI in bivariate analyses but, after adjusting for the confounding factors, only HRSV infection and younger age were independently associated with LRTI. The prevalence of HRSV is high among children visiting the PGHB for ARI. HRSV infection and lower age are independently associated with the risk of ARI being diagnosed as LRTI.

Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study.

PubMed

Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M; Ajami, Nadim J; Espinola, Janice A; Petrosino, Joseph F; Piedra, Pedro A; Stevenson, Michelle D; Sullivan, Ashley F; Thompson, Amy D; Camargo, Carlos A

2017-11-01

Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants. A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64-24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26-22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses. In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile

Role of viral coinfections in asthma development.

PubMed

Garcia-Garcia, Maria Luz; Calvo, Cristina; Ruiz, Sara; Pozo, Francisco; Del Pozo, Victoria; Remedios, Laura; Exposito, Nadia; Tellez, Ana; Casas, Inmaculada

2017-01-01

Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections. Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis. Median current age at follow-up was 7.3 years (IQR: 6.7-8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001), and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01). Asthma at 6-8 years is more frequent and severe in those children previously hospitalized with viral

Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine.

PubMed

Glenn, Gregory M; Smith, Gale; Fries, Louis; Raghunandan, Rama; Lu, Hanxin; Zhou, Bin; Thomas, D Nigel; Hickman, Somia P; Kpamegan, Eloi; Boddapati, Sarathi; Piedra, Pedro A

2013-01-07

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. Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) 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. 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. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

PubMed

Kokturk, Nurdan; Bozdayi, Gulendam; Yilmaz, Senay; Doğan, Bora; Gulbahar, Ozlem; Rota, Seyyal; Tatlicioglu, Turkan

2015-08-01

Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.

Antigen-dependent proliferation and cytokine induction in respiratory syncytial virus-infected cotton rats reflect the presence of effector-memory T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richter, Bettina W.M.; Onuska, Jaya M.; Niewiesk, Stefan

2005-06-20

Respiratory syncytial virus (RSV) is a major cause of lower airway disease in infants and children. Immunity to RSV is not long lasting, resulting in re-occurring infections throughout life. Effective long-lived immunity results when central-memory T cells that proliferate vigorously and secrete IL-2 are present. In contrast, effector-memory T cells that mainly produce IFN-{gamma}, facilitate virus clearance but are not long lived. To identify the type of memory response induced after RSV-A (Long) infection, we characterized the kinetics of the antigen-specific immune response and identified the types of cytokines induced. RSV-specific lymphocytic proliferation following primary and secondary infection was similar,more » and in both cases responses waned within a short period of time. In addition, mRNA for IFN-{gamma} but not IL-2 was induced in RSV-specific CD4{sup +} T cells. This supports the idea that the presence of effector-memory rather than central-memory T cells contributes to the ineffectiveness of the immune response to RSV.« less

The transmission dynamics of groups A and B human respiratory syncytial virus (hRSV) in England & Wales and Finland: seasonality and cross-protection.

PubMed

White, L J; Waris, M; Cane, P A; Nokes, D J; Medley, G F

2005-04-01

Human respiratory syncytial virus (hRSV) transmission dynamics are inherently cyclical, and the observed genetic diversity (between groups A and B) also appears to have a repeating pattern. A key unknown is the extent to which genetic variants interact immunologically, and thus impact on epidemiology. We developed a novel mathematical model for hRSV transmission including seasonal forcing of incidence and temporary intra- and inter-group partial immunity. Simultaneous model fits to data from two locations (England & Wales, UK, and Turku, Finland) successfully reproduced the contrasting infection dynamics and group A/B dominance patterns. Parameter estimates are consistent with direct estimates. Differences in the magnitude and seasonal variation in contact rate between the two populations alone could account for the variation in dynamics between these populations. The A/B group dominance patterns are explained by reductions in susceptibility to and infectiousness of secondary homologous and heterologous infections. The consequences of the observed dynamic complexity are discussed.

Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru

PubMed Central

Wu, Andrew; Budge, Philip J.; Williams, John; Griffin, Marie R.; Edwards, Kathryn M.; Johnson, Monika; Zhu, Yuwei; Hartinger, Stella; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Grijalva, Carlos G.

2015-01-01

Introduction The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Materials and Methods We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression. Results Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). Conclusion In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional

Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.

PubMed

Wu, Andrew; Budge, Philip J; Williams, John; Griffin, Marie R; Edwards, Kathryn M; Johnson, Monika; Zhu, Yuwei; Hartinger, Stella; Verastegui, Hector; Gil, Ana I; Lanata, Claudio F; Grijalva, Carlos G

2015-01-01

The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression. Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among

Prospective study on antibiotics misuse among infants with upper respiratory infections.

PubMed

El Sayed, Manal F; Tamim, Hala; Jamal, Diana; Mumtaz, Ghina; Melki, Imad; Yunis, Khalid

2009-06-01

The judicious prescription of antibiotics has become a central focus of professional and public health measures to combat the spread of resistant organisms. A one-year multi-center prospective follow-up study of 1,320 healthy infants was conducted. The study aim was to determine the prevalence and identify the predictors of antibiotics misuse in viral respiratory illnesses among healthy infants in the first year of life. Infants born between August 2001 and February 2002 were recruited through the clinics and dispensaries of 117 pediatricians located in the Greater Beirut area of Lebanon. On each routine visit from birth until one year of life, pediatricians reported any episodes of upper respiratory tract infection (URTI; common cold) and bronchiolitis, as well as the treatment type, duration, and dose. Predictors that were considered included infant, maternal, and pediatrician characteristics. Of the 1,320 recruited infants, 770 (58.3%) had common cold or acute bronchiolitis on at least one occasion during the study period. Pediatricians prescribed antibiotics at least once in 21.4% of cases diagnosed as the common cold and 45.5% of cases of acute bronchiolitis. Logistic regression analysis revealed that antibiotics misuse was more common among infants born to mothers with lower educational levels (odds ratio [OR] = 1.6; 95% confidence interval [CI]: 1.1-2.3). Furthermore, pediatricians tend to prescribe antibiotics in dispensaries more often than in private clinics (OR = 1.4; 95% CI: 1.0-2.3). This study shows a substantial quantity of antibiotics prescriptions for common cold and acute bronchiolitis in our population. Our findings suggest that lower maternal education and pediatricians working in dispensaries (versus private clinics) are associated with increased antibiotics misuse.

Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study.

PubMed

Madhi, Shabir A; Cutland, Clare L; Downs, Sarah; Jones, Stephanie; van Niekerk, Nadia; Simoes, Eric A F; Nunes, Marta C

2018-05-17

Limited data exist on the burden of respiratory syncytial virus (RSV) illness among pregnant women, to determine their potential benefit from RSV vaccination. We evaluated the incidence of RSV illness from midpregnancy until 24 weeks postpartum in human immunodeficiency virus (HIV)-uninfected and HIV-infected women and their infants. Mother-infant dyads were enrolled in maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV. The incidence (per 1000 person-months) of RSV illness (n = 43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95% confidence interval [CI], .6-2.2) than in 2012 (4.0; 95% CI, 2.8-5.6). The incidence of RSV illness (n = 5) in HIV-infected women was 3.4 (95% CI, 1.4-8.1). Maternal RSV infection was associated with respiratory symptoms including cough (72.1%), rhinorrhea (39.5%), sore throat (37.2%), and headache (42%), but fever was absent. RSV infection during pregnancy was not associated with adverse pregnancy outcomes. Postpartum, RSV infection in mothers (n = 27) was associated with concurrent infection among 51.9% of their infants and, conversely, 29.8% of mothers investigated within 7 days of their infants having an RSV illness also tested positive for RSV. RSV infection is associated with respiratory illness during pregnancy and postpartum. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against nonfebrile illness, and her infant. NCT01306669 and NCT01306682.

Predicting Appropriate Admission of Bronchiolitis Patients in the Emergency Department: Rationale and Methods.

PubMed

Luo, Gang; Stone, Bryan L; Johnson, Michael D; Nkoy, Flory L

2016-03-07

In young children, bronchiolitis is the most common illness resulting in hospitalization. For children less than age 2, bronchiolitis incurs an annual total inpatient cost of $1.73 billion. Each year in the United States, 287,000 emergency department (ED) visits occur because of bronchiolitis, with a hospital admission rate of 32%-40%. Due to a lack of evidence and objective criteria for managing bronchiolitis, ED disposition decisions (hospital admission or discharge to home) are often made subjectively, resulting in significant practice variation. Studies reviewing admission need suggest that up to 29% of admissions from the ED are unnecessary. About 6% of ED discharges for bronchiolitis result in ED returns with admission. These inappropriate dispositions waste limited health care resources, increase patient and parental distress, expose patients to iatrogenic risks, and worsen outcomes. Existing clinical guidelines for bronchiolitis offer limited improvement in patient outcomes. Methodological shortcomings include that the guidelines provide no specific thresholds for ED decisions to admit or to discharge, have an insufficient level of detail, and do not account for differences in patient and illness characteristics including co-morbidities. Predictive models are frequently used to complement clinical guidelines, reduce practice variation, and improve clinicians' decision making. Used in real time, predictive models can present objective criteria supported by historical data for an individualized disease management plan and guide admission decisions. However, existing predictive models for ED patients with bronchiolitis have limitations, including low accuracy and the assumption that the actual ED disposition decision was appropriate. To date, no operational definition of appropriate admission exists. No model has been built based on appropriate admissions, which include both actual admissions that were necessary and actual ED discharges that were unsafe. The

Predictors and incidence of hospitalization due to respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI) in non-prophylaxed moderate-to-late preterm infants in Bosnia and Herzegovina.

PubMed

Maksić, Hajrija; Heljić, Suada; Skokić, Fahrija; Šumanović-Glamuzina, Darinka; Milošević, Veroslava; Zlatanović, Almir; Gerard, Notario

2018-04-27

Prematurity is a risk factor for respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs), due to immature humoral and cell-mediated immune system in preterm newborns, as well as their incomplete lung development. Palivizumab, a humanized monoclonal antibody against the F glycoprotein of RSV, is licensed for the prevention of severe RSV LRTI in children at high risk for the disease. This study is a part of a larger observational, retrospective-prospective epidemiological study (PONI) conducted at 72 sites across 23 countries in the northern temperate zone. The aim of our non-interventional study was to identify common predictors and factors associated with RSV LRTI hospitalization in non-prophylaxed, moderate-to-late preterm infants, born between 33 weeks and 0 days and 35 weeks and 6 days of gestation, and less than 6 months prior to or during the RSV season in Bosnia and Herzegovina (B&H). A total of 160 moderate-to-late preterm infants were included from four sites in B&H (Sarajevo, Tuzla, Mostar, and Banja Luka). We identified several significant intrinsic and extrinsic factors to be associated with the risk of RSV LRTI hospitalization in the preterm infants, including: comorbidities after birth, shorter hospital stay, admission to NICU/PICU while in the maternity ward, household smoking, low maternal age, breast feeding, number of family members, and history of family/paternal atopy. Overall, our results indicated that the risk of RSV LRTI in preterm newborns can be associated with different environmental and social/cultural factors, and further research is needed to comprehensively evaluate these associations.

Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

This study investigated viruses in bovine respiratory disease (BRD) cases in feedlots, including bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). Nasal swabs were collected fro...

Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice.

PubMed

Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

2016-10-21

The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC 50 ) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC 50 ) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect.

Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice

PubMed Central

Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

2016-01-01

The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect. PMID:27767097

Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples.

PubMed

Arvia, Rosaria; Corcioli, Fabiana; Ciccone, Nunziata; Della Malva, Nunzia; Azzi, Alberta

2015-12-01

Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 10(3) copies/ml to 10(4) copies/ml. For parainfluenza virus 2 only it was 10(5) copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be

ROLE OF MONOCYTES AND EOSINOPHILS IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION

EPA Science Inventory

Role of Monocytes and Eosinophils
in Respiratory Syncytial Virus (RSV) Infection

Joleen M. Soukup and Susanne Becker

US Environmental Protection Agency, National Health and Environmental
Effects Research Laboratory, Research Triangle Park, NC 27711;
...