WorldWideScience

Sample records for bovine respiratory syncytial

  1. Bovine respiratory syncytial virus (BRSV): A review

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) infection is the major cause of respiratory disease in calves during the first year of life. The study of the virus has been difficult because of its lability and very poor growth in cell culture. However, during the last decade, the introduction of new...... complex and unpredictable which makes the diagnosis and subsequent therapy very difficult. BRSV is closely related to human respiratory syncytial virus (HRSV) which is an important cause of respiratory disease in young children. In contrast to BRSV, the recent knowledge of HRSV is regularly extensively...

  2. Evolution of Bovine Respiratory Syncytial Virus

    Science.gov (United States)

    Valarcher, Jean-François; Schelcher, François; Bourhy, Hervé

    2000-01-01

    Until now, the analysis of the genetic diversity of bovine respiratory syncytial virus (BRSV) has been based on small numbers of field isolates. In this report, we determined the nucleotide and deduced amino acid sequences of regions of the nucleoprotein (N protein), fusion protein (F protein), and glycoprotein (G protein) of 54 European and North American isolates and compared them with the sequences of 33 isolates of BRSV obtained from the databases, together with those of 2 human respiratory syncytial viruses and 1 ovine respiratory syncytial virus. A clustering of BRSV sequences according to geographical origin was observed. We also set out to show that a continuous evolution of the sequences of the N, G, and F proteins of BRSV has been occurring in isolates since 1967 in countries where vaccination was widely used. The exertion of a strong positive selective pressure on the mucin-like region of the G protein and on particular sites of the N and F proteins is also demonstrated. Furthermore, mutations which are located in the conserved central hydrophobic part of the ectodomain of the G protein and which result in the loss of four Cys residues and in the suppression of two disulfide bridges and an α helix critical to the three-dimensional structure of the G protein have been detected in some recent French BRSV isolates. This conserved central region, which is immunodominant in BRSV G protein, thus has been modified in recent isolates. This work demonstrates that the evolution of BRSV should be taken into account in the rational development of future vaccines. PMID:11044116

  3. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik

    2002-01-01

    Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus...... and the infections with human respiratory syncytial. virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication...... and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...

  4. Serological responses in calves to vaccines against bovine respiratory syncytial, infectious bovine rhinotracheitis, bovine viral diarrhoea and parainfluenza-3 viruses.

    Science.gov (United States)

    Tollis, M; Di Trani, L; Cordioli, P; Vignolo, E; Di Pasquale, I

    1996-01-01

    The Istituto Superiore di Sanità (ISS), the National Veterinary Services Laboratory in Italy, is in charge of assessing the quality, safety and efficacy of veterinary vaccines before and after licensing. To evaluate the relative potency of several vaccines against bovine respiratory syncytial virus (BRSV), infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhoea virus (BVDV) and parainfluenza-3 virus (PI3V), the serological responses in vaccinated calves were studied. Vaccination with any of the vaccines under study induced specific antibody titres against the different viral antigens. The differences of the mean antibody titres within and among the test group vaccines were statistically significant. The results confirm and support those obtained by other authors in similar studies, suggesting that serological responses in vaccinated calves can be used as a helpful means of assessing the relative potency of vaccines against viral respiratory diseases of cattle. The criteria allowing such an evaluation are discussed.

  5. Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tegtmeier, C.; Pedersen, E.

    2001-01-01

    The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the o...... beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later.......The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior...... to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested...

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

    Science.gov (United States)

    Klem, Thea B; Rimstad, Espen; Stokstad, Maria

    2014-01-14

    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. 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. 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.

  7. Bovine respiratory disease associated with Histophilus somni and bovine respiratory syncytial virus in a beef cattle feedlot from Southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Selwyn Arligton Headley

    2017-03-01

    Full Text Available Bovine respiratory disease (BRD is a complex multifactorial and multi-etiological disease entity that is responsible for the morbidity and mortality particularly in feedlot cattle from North America. Information relative to the occurrence of BRD in Brazil and the associated infectious agents are lacking. This study investigated the participation of infectious agents of BRD in a beef cattle feedlot from Southeastern Brazil. Nasopharyngeal swabs of 11% (10/90 of cattle (n, 450 with clinical manifestations of respiratory distress were analyzed by targeting specific genes of the principal infectious pathogens of BRD. In addition, pulmonary fragments of one the animals that died were collected for histopathological and molecular diagnoses. The nucleic acids of Histophilus somni and bovine respiratory syncytial virus (BRSV were identified in 20% (2/10 of the nasopharyngeal swabs of the animals with respiratory distress; another contained only BRSV RNA. Moreover, the nucleic acids of both infectious agents were amplified from the pulmonary fragments of the animal that died with histopathological evidence of bronchopneumonia and interstitial pneumonia; the nasopharyngeal swab of this animal also contained the nucleic acids of both pathogens. Additionally, all PCR and/or RT-PCR assays designed to detect the specific genes of Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine viral diarrhea virus, bovine herpesvirus -1, bovine parainfluenza virus-3, and bovine coronavirus yielded negative results. Phylogenetic analyses suggest that the isolates of H. somni circulating in Brazil are similar to those identified elsewhere, while there seem to be diversity between the isolates of BRSV within cattle herds from different geographical locations of Brazil.

  8. DETECTION OF BOVINE RESPIRATORY SYNCYTIAL VIRUS IN CALVES OF RIO GRANDE DO SUL, BRAZIL

    Directory of Open Access Journals (Sweden)

    Ivan Paulo Demartini Gonçalves

    1993-12-01

    Full Text Available During 20 months of the 1987-1990 period, lung tissue samples from 351 calves were obtained at a slaughterhouse. These calves were from counties nearby Porto Alegre. The direct and indirect fluorescent antibody tests (FAT using polyclonal and monoclonal antibody conjugates were performed on frozen lung sections. Eighteen (5.13% of the calf lung samples were positive for the Bovine Respiratory Syncytial Virus (BRSV. The BRSV was isolated from FAT positive samples.

  9. Bovine respiratory syncytial virus ISCOMs - protection in the presence of maternal antibodies

    DEFF Research Database (Denmark)

    Hägglund, Sara; Hu, Ke-Fei; Larsen, Lars Erik

    2004-01-01

    The protection induced by immunostimulating complexes (ISCOMs) against bovine respiratory syncytial virus (BRSV) was evaluated and compared to that of a commercial inactivated vaccine (CV) in calves with BRSV-specific maternal antibodies. Following experimental challenge, controls (n = 4......) and animals immunized with CV (n = 5) developed moderate to severe respiratory disease, whereas calves immunized with ISCOMS (17 = 5) remained clinically healthy. BRSV was re-isolated from the nasopharynx of all controls and from all calves immunized with CV, but from none of the calves immunized with ISCOMs...... of maternal antibodies in calves and induced strong clinical and virological protection against a BRSV challenge....

  10. Extensive sequence divergence among bovine respiratory syncytial viruses isolated during recurrent outbreaks in closed herds

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    2000-01-01

    The nucleotides coding for the extracellular part of the G glycoprotein and the full SH protein of bovine respiratory syncytial virus (BRSV) were sequenced from viruses isolated from numerous outbreaks of BRSV infection. The isolates included viruses isolated from the same herd (closed dairy farms......, however, the most likely explanation was that BRSV was (re)introduced into the herd prior to each new outbreak These findings are highly relevant for the understanding of the transmission patterns of BRSV among calves and human respiratory syncytial virus among humans....... and veal calf production units) in different years and from all confirmed outbreaks in Denmark within a short period. The results showed that identical viruses were isolated within a herd during outbreaks and that viruses from recurrent infections varied by up to 11% in sequence even in closed herds...

  11. Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and conventional dairy herds.

    Science.gov (United States)

    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

  12. Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Rontved, C. M.; Tjørnehøj, Kirsten; Viuff, B.

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves...

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

    Science.gov (United States)

    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.

  14. The association between serological titers in infectious bovine rhinotracheitis virus, bovine virus diarrhea virus, parainfluenza-3 virus, respiratory syncytial virus and treatment for respiratory disease in Ontario feedlot calves.

    OpenAIRE

    Martin, S W; Bohac, J G

    1986-01-01

    A seroepidemiological study of the association between antibody titers to infectious bovine rhinotracheitis, parainfluenza-3, bovine virus diarrhea and bovine respiratory syncytial viruses, and treatment for bovine respiratory disease was conducted. A total of 322 calves from five different groups were bled on arrival, then one month later all cases (cattle treated for bovine respiratory disease) were rebled together with an equal number of controls (cattle not treated for any disease). Titer...

  15. Respiratory syncytial virus (RSV)

    Science.gov (United States)

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

  16. Antibody responses against epitopes on the F protein of bovine respiratory syncytial virus differ in infected or vaccinated cattle

    NARCIS (Netherlands)

    Schrijver, R.S.; Hensen, E.J.; Langedijk, J.P.M.; Daus, F.; Middel, W.G.J.; Kramps, J.A.; Oirschot, van J.T.

    1997-01-01

    The fusion protein F of bovine respiratory syncytial virus (BRSV) is an important target for humoral and cellular immune responses, and antibodies against the F protein have been associated with protection. However, the F protein can induce antibodies with different biological activity, possibly

  17. Antiviral effects of bovine interferons on bovine respiratory tract viruses.

    OpenAIRE

    Fulton, R W; Downing, M M; Cummins, J M

    1984-01-01

    The antiviral effects of bovine interferons on the replication of bovine respiratory tract viruses were studied. Bovine turbinate monolayer cultures were treated with bovine interferons and challenged with several bovine herpesvirus 1 strains, bovine viral diarrhea virus, parainfluenza type 3 virus, goat respiratory syncytial virus, bovine respiratory syncytial virus, bovine adenovirus type 7, or vesicular stomatitis virus. Treatment with bovine interferons reduced viral yield for each of the...

  18. Parainfluenza-3 and bovine respiratory syncytial virus: intraherd correlation adjusted for sensitivity and specificity

    Directory of Open Access Journals (Sweden)

    José Segura C.

    2013-11-01

    Full Text Available Objective. The purpose of this study was to compare the intra-class correlation coefficients (ICC and design effects (D estimates adjusted or unadjusted for sensibility (Se and specificity (Sp of the diagnostic tests using a Bayesian procedure. Materials and methods. Sera from 232 animals from 44 randomly selected herds, to detect antibodies against parainfluenza-3 virus (PIV3 from non-vaccinated dual-purpose cattle from Colima Mexico, were used. Only 176 animals from 33 herds were used to evaluate the presence of the bovine respiratory syncytial virus (BRSV. Results. The ICC and D values adjusted and unadjusted for PIV3 were 0.33, 2.73, 0.32, and 2.71, respectively. For BRSV the values were 0.31, 2.64, 0.28 and 2.49. Conclusions. The adjusted or unadjusted ICC and D estimates were similar because of the high Se and Sp of the diagnostic tests and the relatively high prevalence of the diseases here studied.

  19. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model.

    Directory of Open Access Journals (Sweden)

    Paul Walsh

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2 which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase.We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected.We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed.One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p<0.01 and weight gain (p = 0.08 seemed better in the ibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen.Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes

  20. A randomized placebo controlled trial of ibuprofen for respiratory syncytial infection in a bovine model study

    Science.gov (United States)

    Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to ...

  1. Quantitative trait loci associated with the immune response to a bovine respiratory syncytial virus vaccine.

    Directory of Open Access Journals (Sweden)

    Richard J Leach

    Full Text Available Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501 which was genotyped for 165 microsatellite markers (covering all autosomes to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected.Heifers from the same population (n = 195 were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA, and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the

  2. Spatial patterns of Bovine Corona Virus and Bovine Respiratory Syncytial Virus in the Swedish beef cattle population

    Directory of Open Access Journals (Sweden)

    Björkman Camilla

    2010-05-01

    Full Text Available Abstract Background Both bovine coronavirus (BCV and bovine respiratory syncytial virus (BRSV infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. Methods Blood samples were collected from 2,763 animals located in 2,137 herds and analyzed for presence of antibodies to BCV and BRSV. Moran's I was calculated to assess spatial autocorrelation, and identification of geographical cluster was performed using spatial scan statistics. Results Animals detected positive to BCV or BRSV were predominately located in the central-western and some southern parts of Sweden. Moran's I indicated global spatial autocorrelation. BCV and BRSV appeared to be spatially related: two areas in southern Sweden (Skaraborg and Skåne had a significantly higher prevalence of BCV (72.5 and 65.5% respectively; almost the same two areas were identified as being high-prevalence clusters for BRSV (69.2 and 66.8% respectively. An area in south-east Sweden (Kronoberg-Blekinge had lower prevalences for both infections than expected (23.8 and 20.7% for BCV and BRSV respectively. Another area in middle-west Sweden (Värmland-Dalarna had also a lower prevalence for BRSV (7.9%. Areas with beef herd density > 10 per 100 km2 were found to be at significantly higher risk of being part of high-prevalence clusters. Conclusion These results form a basis for further investigations of between-herds dynamics and risk factors for these infections in order to design effective control strategies.

  3. Respiratory Syncytial Virus

    Science.gov (United States)

    ... When to Call the Doctor en español Virus respiratorio sincitial About RSV Respiratory syncytial (sin-SISH-ul) ... diseases that affect the lungs, heart, or immune system , RSV infections can lead to other more serious ...

  4. Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge

    NARCIS (Netherlands)

    Antonis, A.F.G.; Most, van der R.G.; Suezer, Y.; Stockhofe-Zurwieden, N.; Daus, F.J.; Sutter, G.; Schrijver, R.S.

    2007-01-01

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and calves. Bovine RSV (bRSV) is a natural pathogen for cattle, and bRSV infection in calves shares many features with the human infection. Thus, bRSV infection in cattle provides the ideal setting to

  5. Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in young conventional calves.

    Science.gov (United States)

    Hägglund, Sara; Hu, Kefei; Vargmar, Karin; Poré, Lesly; Olofson, Ann-Sophie; Blodörn, Krister; Anderson, Jenna; Ahooghalandari, Parvin; Pringle, John; Taylor, Geraldine; Valarcher, Jean-François

    2011-11-03

    Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe. Commercial vaccines against this virus needs improvement of efficacy, especially in calves with BRSV-specific maternally derived antibodies (MDA). We previously reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine, induced strong clinical and virological protection in calves with MDA, immunized at 7-15 weeks of age. The aim of the present study was to characterize the immune responses, as well as to investigate the efficacy and safety in younger animals, representing the target population for vaccination. Four groups of five 3-8 week old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii) BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection. The cellular and humoral responses were monitored as well as the clinical signs, the viral excretion and the pathology following challenge. Despite presence of MDA at the time of the immunization, only a minimum of clinical signs were observed in the BRSV-ISCOM group after challenge. In contrast, in all control groups, clinical signs of disease were observed in most of the animals (respiratory rates up to 76min(-1) and rectal temperatures up to 41°C). The clinical protection was associated to a highly significant reduction of virus replication in the upper and lower respiratory tract of calves, rapid systemic and local antibody responses and T helper cell responses dominated by IFNγ production. Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. The protective immunological responses to BRSV proteins and the ability to overcome the inhibiting effect of

  6. One-step multiplex real time RT-PCR for the detection of bovine respiratory syncytial virus, bovine herpesvirus 1 and bovine parainfluenza virus 3.

    Science.gov (United States)

    Thonur, Leenadevi; Maley, Madeleine; Gilray, Janice; Crook, Tara; Laming, Ellie; Turnbull, Dylan; Nath, Mintu; Willoughby, Kim

    2012-03-28

    Detection of respiratory viruses in veterinary species has traditionally relied on virus detection by isolation or immunofluorescence and/or detection of circulating antibody using ELISA or serum neutralising antibody tests. Multiplex real time PCR is increasingly used to diagnose respiratory viruses in humans and has proved to be superior to traditional methods. Bovine respiratory disease (BRD) is one of the most common causes of morbidity and mortality in housed cattle and virus infections can play a major role. We describe here a one step multiplex reverse transcriptase quantitative polymerase chain reaction (mRT-qPCR) to detect the viruses commonly implicated in BRD. A mRT-qPCR assay was developed and optimised for the simultaneous detection of bovine respiratory syncytial virus (BRSV), bovine herpes virus type 1 (BoHV-1) and bovine parainfluenza virus type 3 (BPI3 i & ii) nucleic acids in clinical samples from cattle. The assay targets the highly conserved glycoprotein B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using in vitro transcribed RNA and recent field isolates. For clinical validation, 541 samples from clinically affected animals were tested and mRT-qPCR result compared to those obtained by conventional testing using virus isolation (VI) and/or indirect fluorescent antibody test (IFAT). The mRT-qPCR assay was rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 102 copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to detect the three primary viral agents of BRD and the first multiplex designed using locked nucleic acid (LNA), minor groove binding (MGB) and TaqMan probes in one reaction mix. This test was more sensitive than both VI and IFAT and can replace the aforesaid methods for virus detection during outbreaks of BRD.

  7. Establishing presence of antibodies against bovine respiratory syncytial virus (BRSV, parainfluenza virus 3 (PI3 and bovine herpesvirus 1 (BHV 1 in blood serum of cattle using indirect immunoenzyme probe

    Directory of Open Access Journals (Sweden)

    Šamanc Horea

    2009-01-01

    Full Text Available A total of 92 samples of bovine blood serum were examined for the presence of antibodies against the bovine respiratory syncytial virus using indirect immunoenzyme probe - iELISA. Specific antibodies against the bovine respiratory syncytial virus (BRSV were established in 46, or 50% blood serum samples. Investigations of the 92 blood serum samples of cattle for the presence of antibodies against the parainfluenza virus 3 (PI 3, revealed their presence in 77, or 83.69% of the samples, and the presence of antibodies against the bovine herpesvirus 1 (BHV 1 was established in 19, or 20.65% of the samples.

  8. Sites of replication of bovine respiratory syncytial virus in naturally infected calves as determined by in situ hybridization

    DEFF Research Database (Denmark)

    Viuff, B.; Uttenthal, Åse; Tegtmeier, C.

    1996-01-01

    Replication of bovine respiratory syncytial virus (BRSV) was studied in three naturally infected calves by in situ hybridization using strand-specific RNA probes. One of the calves was a 5-month-old Friesian, the other two calves were a 3-month-old and a 2-week-old Jersey. Two Jersey calves, 3...... months and 3 weeks of age, served as controls. Replication of BRSV took place in the luminal lining of the respiratory tract. In one of the BRSV infected animals (calf No. 1), replication was especially seen in the bronchi, whereas in the two other animals (calf Nos. 2 and 3) replication of BRSV...... was detected. In tissue outside the respiratory tract neither BRSV antigen nor replication of BRSV could be demonstrated....

  9. One-step multiplex real time RT-PCR for the detection of bovine respiratory syncytial virus, bovine herpesvirus 1 and bovine parainfluenza virus 3

    Directory of Open Access Journals (Sweden)

    Thonur Leenadevi

    2012-03-01

    Full Text Available Abstract Background Detection of respiratory viruses in veterinary species has traditionally relied on virus detection by isolation or immunofluorescence and/or detection of circulating antibody using ELISA or serum neutralising antibody tests. Multiplex real time PCR is increasingly used to diagnose respiratory viruses in humans and has proved to be superior to traditional methods. Bovine respiratory disease (BRD is one of the most common causes of morbidity and mortality in housed cattle and virus infections can play a major role. We describe here a one step multiplex reverse transcriptase quantitative polymerase chain reaction (mRT-qPCR to detect the viruses commonly implicated in BRD. Results A mRT-qPCR assay was developed and optimised for the simultaneous detection of bovine respiratory syncytial virus (BRSV, bovine herpes virus type 1 (BoHV-1 and bovine parainfluenza virus type 3 (BPI3 i & ii nucleic acids in clinical samples from cattle. The assay targets the highly conserved glycoprotein B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using in vitro transcribed RNA and recent field isolates. For clinical validation, 541 samples from clinically affected animals were tested and mRT-qPCR result compared to those obtained by conventional testing using virus isolation (VI and/or indirect fluorescent antibody test (IFAT. Conclusions The mRT-qPCR assay was rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 102 copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to detect the three primary viral agents of BRD and the first multiplex designed using locked nucleic acid (LNA, minor groove binding (MGB and TaqMan probes in one reaction mix. This test was more sensitive than both VI and IFAT and can replace the aforesaid methods for virus detection during outbreaks of BRD.

  10. Respiratory Syncytial Virus Vaccines

    OpenAIRE

    Dudas, Robert A; Karron, Ruth A.

    1998-01-01

    Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...

  11. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    2013-02-04

    Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDC’s Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.  Created: 2/4/2013 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases (DVD).   Date Released: 2/13/2013.

  12. Systematic review and meta-analysis of the effectiveness of commercially available vaccines against bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus for mitigation of bovine respiratory disease complex in cattle.

    Science.gov (United States)

    Theurer, Miles E; Larson, Robert L; White, Brad J

    2015-01-01

    To evaluate and analyze data from controlled studies on the effectiveness of vaccinating cattle with commercially available viral antigen vaccines for mitigation of the effects of bovine respiratory disease complex (BRDC). Systematic review and meta-analysis. 31 studies comprising 88 trials. Studies that reported the effectiveness of commercially available bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and parainfluenza type 3 virus (PI3) vaccines for protection of cattle against BRDC or its components were included in the analysis. Studies or trials were categorized as natural exposure or experimental challenge and were further divided by the viral antigen evaluated and vaccine type (modified-live virus [MLV] or inactivated vaccine). Meta-analysis was performed; summary Mantel-Haenszel risk ratios were determined, and Forest plots were generated. In natural exposure trials, beef calves vaccinated with various antigen combinations had a significantly lower BRDC morbidity risk than did nonvaccinated control calves. In trials evaluating BHV-1 and MLV BVDV vaccines in experimental challenge models, vaccinated calves had a lower BRDC morbidity risk than did control calves; however, in experimental challenge trials evaluating MLV BRSV and PI3 vaccines, no significant difference in morbidity or mortality risk was found between vaccinated and control calves. Estimating clinical efficacy from results of experimental challenge studies requires caution because these models differ substantially from those involving natural exposure. The literature provides data but does not provide sufficiently strong evidence to guide definitive recommendations for determining which virus components are necessary to include in a vaccination program for prevention or mitigation of BRDC in cattle.

  13. Learn about Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... Lung Health and Diseases > Lung Disease Lookup > RSV Learn About Respiratory Syncytial Virus (RSV) Respiratory syncytial virus ( ... file."); } }); } } --> Blank Section Header Lung Disease Lookup RSV Learn About Respiratory Syncytial Virus (RSV) RSV Symptoms, Causes & ...

  14. Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

    Science.gov (United States)

    Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

    2010-05-14

    The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Jeng, M J; Lemen, R J

    1997-03-01

    Respiratory syncytial virus (RSV) bronchiolitis is associated with the clinical signs and symptoms of small airway obstruction. A major public health problem throughout the world, this condition is responsible for significant morbidity and mortality. Management is primarily preventive, through strict hand washing, avoidance of exposure during the respiratory illness season and intravenously administered prophylactic anti-RSV Immune globulin, especially in selected small infants with underlying cardiopulmonary disease. Supportive measures, including fluid hydration, good nutrition, aerosolized bronchodilators and steroids, may be helpful. Ribavirin may be useful in severely ill children or those with underlying cardiopulmonary disease. A significant number of patients have recurrent episodes of bronchiolitis and wheezing, and may develop asthma later in life. Avoidance of exposure to tobacco smoke, cold air and air pollutants is also beneficial to long-term recovery from RSV bronchiolitis. A number of vaccines to prevent this infection are currently being studied.

  16. 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

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Breum, Solvej Østergaard; Larsen, Lars Erik

    2012-01-01

    Background 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. Findings 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...

  17. The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.

    2000-01-01

    The ability of a pure virus infection to induce an acute phase protein response is of interest as viral infections are normally considered to be less efficient in inducing an acute phase protein response than bacterial infections. This was studied in a bovine model for infection with bovine...... respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7-8 days after inoculation of BRSV, while no response...... was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response...

  18. 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

    Directory of Open Access Journals (Sweden)

    Salomonsen Charlotte M

    2012-11-01

    Full Text Available Abstract Background 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. Findings 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. Conclusions This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  19. 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.

    Science.gov (United States)

    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.

  20. Chimeric Bovine Respiratory Syncytial Virus with Attachment and Fusion Glycoproteins Replaced by Bovine Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase and Fusion Proteins

    Science.gov (United States)

    Stope, Matthias B.; Karger, Axel; Schmidt, Ulrike; Buchholz, Ursula J.

    2001-01-01

    Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of the Respirovirus genus can together functionally replace their homologs in a Pneumovirus background. PMID:11533200

  1. An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves

    DEFF Research Database (Denmark)

    Tjørnehøj, Kirsten; Uttenthal, Åse; Viuff, B.

    2003-01-01

    Bovine respiratory syncytial virus (BRSV) has been recognised as an important pathogen in calf pneumonia for 30 years, but surprisingly few effective infection models for studies of the immune response and the pathogenesis in the natural host have been established. We present a reproducible...... experimental infection model for BRSV in 2-5-month-old, conventionally reared Jersey calves. Thirty-four colostrum-fed calves were inoculated once by aerosol and intratracheal injection with BRSV. Respiratory disease was recorded in 91% of the BRSV-inoculated calves, 72% had an accompanying rise in rectal...... temperature and 83% exhibited >5%, consolidation of the lung tissue. The disease closely resembled natural outbreaks of BRSV-related pneumonia, and detection of BRSV in nasal secretions and lung tissues confirmed the primary role of BRSV. Nine mock-inoculated control calves failed to develop respiratory...

  2. Diagnosis of enzootic pneumonia in Danish cattle: reverse transcription-polymerase chain reaction assay for detection of bovine respiratory syncytial virus in naturally and experimentally infected cattle

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    1999-01-01

    A reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for detection of bovine respiratory syncytial virus (BRSV) in lung tissue of naturally and experimentally infected cattle. Primers were selected from the gene coding the F fusion protein, which is relatively conserved...... among BRSV isolates. The RT-PCR assay was highly specific, it yielded positive reactions only when performed on BRSV-infected cell cultures or tissues. The detection limit of the RT-PCR assay was assessed as 5 TCID50. BRSV was detected in tissues of the respiratory tract and in the tracheobroncheal...... lymph node of calves euthanized 2-8 days after experimental infection with BRSV, whereas samples of other tissues and samples from mock-infected animals were negative at all time points. Examination of lung samples from 8 different regions of the lungs revealed that although the virus was most often...

  3. Evaluation of a single-tube fluorogenic RT-PCR assay for detection of bovine respiratory syncytial virus in clinical samples

    DEFF Research Database (Denmark)

    Hakhverdyan, Mikhayil; Hägglund, Sara; Larsen, Lars Erik

    2005-01-01

    Bovine respiratory syncytial virus (BRSV) causes severe disease in naive cattle of all ages and is a common pathogen in the respiratory disease complex of calves. Simplified methods for rapid BRSV diagnosis would encourage sampling during outbreaks and would consequently lead to an extended......, antigen ELISA (Ag-ELISA) and virus isolation (VI). Interspersed negative control samples, samples from healthy animals and eight symptomatically or genetically related viruses were all negative, confirming a high specificity of the assay. Taken together, the data indicated that the fRT-PCR assay can...... understanding of the virus. In this study, a BRSV fluorogenic reverse transcription PCR (fRT-PCR) assay, based on TaqMan principle, was developed and evaluated on a large number of clinical samples, representing various cases of natural and experimental BRSV infections. By using a single-step closed-tube format...

  4. Detection of antibodies and risk factors for infection with bovine respiratory syncytial virus and parainfluenza virus 3 in dual-purpose farms in Colima, Mexico.

    Science.gov (United States)

    Figueroa-Chávez, Daniel; Segura-Correa, José C; García-Márquez, Luís Jorge; Pescador-Rubio, Alfonso; Valdivia-Flores, Arturo Gerardo

    2012-10-01

    A cross-sectional study was carried out, from November 2007 to March 2008, to estimate the prevalence of and to determine risk factors associated with bovine syncytial respiratory virus (BRSV) and parainfluenza 3 virus (PIV3) in dual-purpose herds in Colima, México. One hundred and seventy-six sera from 33 herds for PIV3 and 232 sera from 44 herds for BRSV were used. Sera were analyzed by indirect ELISA for the detection of antibodies against BRSV and PIV3 in cattle herds to determine the seroprevalence of respiratory diseases. The apparent and true prevalences for PIV3 were 60.8% and 54.4% and for BRSV 52.2% and 50.8%, respectively. The percentage of herds showing at least one positive animal was 78.7% for PIV3, and 93.2% for BRSV. Age (≤ 12, 13-48, and >48 months old) and respiratory signs (no, yes) showed significant association (P < 0.05) with PIV3 and age with BRSV. This study showed that animals were exposed to both viruses and that age was the main risk factor. The need to establish new vaccination plans to effectively protect cattle against those infections in the state of Colima, Mexico is suggested.

  5. Bovine parainfluenza virus type 3 (PIV3) expressing the respiratory syncytial virus (RSV) attachment and fusion proteins protects hamsters from challenge with human PIV3 and RSV.

    Science.gov (United States)

    Haller, Aurelia A; Mitiku, Misrach; MacPhail, Mia

    2003-08-01

    Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) are the main causes of ubiquitous acute respiratory diseases of infancy and early childhood, causing 20-25 % of pneumonia and 45-50 % of bronchiolitis in hospitalized children. The primary goal of this study was to create an effective and safe RSV vaccine based on utilizing attenuated bovine PIV3 (bPIV3) as a virus vector backbone. bPIV3 had been evaluated in human clinical trials and was shown to be attenuated and immunogenic in children as young as 2 months of age. The ability of bPIV3 to function as a virus vaccine vector was explored further by introducing the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome. The resulting virus, bPIV3/RSV(I), contained an insert of 2900 nt, comprising two translationally competent transcription units. Despite this increase in genetic material, the virus replicated to high titres in Vero cells. This recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3. Such a vaccine would vastly reduce the respiratory disease burden, the associated hospitalization costs and, most importantly, decrease morbidity and mortality of infants, immunocompromised individuals and the elderly.

  6. Development and evaluation of a Luminex multiplex serology assay to detect antibodies to bovine herpes virus 1, parainfluenza 3 virus, bovine viral diarrhoea virus, and bovine respiratory syncytial virus, with comparison to existing ELISA detection methods.

    Science.gov (United States)

    Anderson, Steve; Wakeley, Phil; Wibberley, Guy; Webster, Kath; Sawyer, Jason

    2011-03-07

    Detection of circulating antibodies to bovine herpes virus 1 (BHV-1), parainfluenza 3 virus (PI3V), bovine viral diarrhoea virus (BVDV) and bovine respiratory syncytial virus (BRSV) using ELISA is widely used for veterinary diagnostics and surveillance. In this paper, the potential of a multiplex serology test based on Luminex technology, where all antibodies are simultaneously detected in a single assay was investigated. The performance of "in-house" separate ELISAs which use relatively crude lysates of cultured virus as capture antigens, was compared to the multiplex assay where the same antigens were covalently bound to the fluorescent beads used in the Luminex platform. A panel of field serum samples was tested by the multiplex assay in parallel with the separate routine ELISAs to provide a comparison between tests. The BHV-1 and PI3V components of the multiplex test showed similar sensitivities and specificities to the separate "in-house" ELISAs. The performance of the BVDV and BRSV components was less successful and was attributed to relatively low signal strength for these antigens, leading to higher assay variability and a reduced ability to distinguish positive and negative samples compared to the "in-house" ELISAs. The results illustrated that antigens commonly used successfully in ELISAs cannot always be transferred for use in alternative assay systems. The use of recombinant BVDV E2 protein was investigated and was shown to lead to an appreciable increase in signal strength compared to the use of crude BVDV antigen in the Luminex system. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  7. Respiratory syncytial virus vaccine development

    Science.gov (United States)

    Hurwitz, Julia L

    2011-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral disease in infants and young children. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. The virus is therefore responsible for an estimated 160,000 deaths per year worldwide. Despite half a century of dedicated research, there remains no licensed vaccine product. Herein are described past and current efforts to harness innate and adaptive immune potentials to combat RSV. A plethora of candidate vaccine products and strategies are reviewed. The development of a successful RSV vaccine may ultimately stem from attention to historical lessons, in concert with an integral partnering of immunology and virology research fields. PMID:21988307

  8. Comparison of levels and duration of detection of antibodies to bovine viral diarrhea virus 1, bovine viral diarrhea virus 2, bovine respiratory syncytial virus, bovine herpesvirus 1, and bovine parainfluenza virus 3 in calves fed maternal colostrum or a colostrum-replacement product.

    Science.gov (United States)

    Chamorro, Manuel F; Walz, Paul H; Haines, Deborah M; Passler, Thomas; Earleywine, Thomas; Palomares, Roberto A; Riddell, Kay P; Galik, Patricia; Zhang, Yijing; Givens, M Daniel

    2014-04-01

    Colostrum-replacement products are an alternative to provide passive immunity to neonatal calves; however, their ability to provide adequate levels of antibodies recognizing respiratory viruses has not been described. The objective of this study was to compare the serum levels of IgG at 2 d of age and the duration of detection of antibodies to bovine viral diarrhea virus 1 (BVDV-1), bovine viral diarrhea virus 2 (BVDV-2), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BHV-1), and bovine parainfluenza virus 3 (BPIV-3) in calves fed maternal colostrum (MC) or a colostrum replacement (CR) at birth. Forty newborn male Holstein calves were assigned to the CR or the MC group. Group CR (n = 20) received 2 packets of colostrum replacement (100 g of IgG per 470-g packet), while group MC (n = 20) received 3.8 L of maternal colostrum. Blood samples for detection of IgG and virus antibodies were collected from each calf at birth, at 2 and 7 d, and monthly until the calves became seronegative. Calves in the MC group had greater IgG concentrations at 2 d of age. The apparent efficiency of absorption of IgG was greater in the MC group than in the CR group, although the difference was not significant. Calves in the CR group had greater concentrations of BVDV neutralizing antibodies during the first 4 mo of life. The levels of antibodies to BRSV, BHV-1, and BPIV-3 were similar in the 2 groups. The mean time to seronegativity was similar for each virus in the 2 groups; however, greater variation was observed in the antibody levels and in the duration of detection of immunity in the MC group than in the CR group. Thus, the CR product provided calves with more uniform levels and duration of antibodies to common bovine respiratory viruses.

  9. Detection of antibodies and risk factors for infection with bovine respiratory syncytial virus and parainfluenza virus-3 in beef cattle of Yucatan, Mexico.

    Science.gov (United States)

    Solís-Calderón, J J; Segura-Correa, J C; Aguilar-Romero, F; Segura-Correa, V M

    2007-11-15

    We collected blood samples from 756 > or =2-year-old cattle in 54 herds in Yucatan, Mexico, and used all of those to determine the antibody seroprevalences (in an indirect enzyme-linked inmunosorbance assay) to bovine respiratory syncytial virus (BRSV) and risk factors for animal-level seropositivity. We used 728 of the same samples (from 52 of the same herds) to do the same for parainfluenza virus-3 (PIV3). Cattle were selected by two-stage cluster sampling. Herd-level and animal-level risk factors were obtained through a personal interview. We analyzed the data by using a random-effects multivariable logistic regression model for clustered observations. All herds had at least 3 (BRSV) or 5 (PIV3) seropositive animals. The animal-level true seroprevalences were: 90.8% (86.5, 95.2%) and 85.6% (80.9, 90.4%) for BRSV and PIV3, respectively. Animals in large herds and old animals had the highest odds of being seropositives to BRSV, and those risk factors plus animals born on the farm for PIV3 infection.

  10. THE EPIDEMIOLOGY OF RESPIRATORY SYNCYTIAL VIRUS (RSV ...

    African Journals Online (AJOL)

    d. THE EPIDEMIOLOGY OF. RESPIRATORY SYNCYTIAL VIRUS. (RSV) INFECTIONS IN SOUTH. AFRICAN CHILDREN. Eftyhia Vardas, Duane Blaauw, ... RSV infection requiring hospitalisation were malnutrition, prematurity, age < 6 months, vitamin A deficiency, environmental pollution and congenital heart disease.

  11. Therapy for respiratory tract infections caused by respiratory syncytial virus

    NARCIS (Netherlands)

    van Woensel, J.; Kimpen, J.

    2000-01-01

    Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI.

  12. Therapy for respiratory tract infections caused by respiratory syncytial virus

    NARCIS (Netherlands)

    van Woensel, J; Kimpen, J

    Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI.

  13. Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2008-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) hospitalization is associated with wheeze. OBJECTIVE: To examine the influence of maternally derived RSV neutralizing antibodies in cord blood on RSV hospitalization and recurrent wheeze in infancy. METHODS: Among children from the Danish National Birth...

  14. THE EPIDEMIOLOGY OF RESPIRATORY SYNCYTIAL VIRUS (RSV ...

    African Journals Online (AJOL)

    These include maternal age and education leve1,6 overcrowding,'malnutrition,' indoor air pollution' and parental smoking.to Viral agents are recovered more frequently than bacterial agents from ARl cases and the most frequent virus detected is respiratory syncytial virus. (RSV).to.ll-1< The predominant bacterial agents are ...

  15. Biology of human respiratory syncytial virus: a review | Aliyu | Bayero ...

    African Journals Online (AJOL)

    Acute lower respiratory tract infection is one of the major causes of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) is the single most important viral cause of lower respiratory tract infection during infancy and early childhood worldwide. Respiratory syncytial virus belongs to the ...

  16. Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease

    Science.gov (United States)

    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...

  17. Hilar enlargement in respiratory syncytial virus pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Odita, J.C.; Aghahowa, J.E. (Benin Univ., Benin City (Nigeria). Dept. of Radiology); Nwankwo, M. (Benin Univ., Benin City (Nigeria). Child Health Coll. of Medical Sciences)

    1989-08-01

    The clinical and radiographic features of ten children with hilar enlargement in association with proven Respiratory Syncytial Virus (RSV) infection are described. Hilar enlargement was seen in 10/35 children with RSV infection, and was invariably unilateral and right sided. It is recommended that RSV pneumonia be considered in children with unilateral hilar enlargement if tuberculosis has been excluded, and the onset of disease is rapid. (orig.).

  18. Lobar collapse with respiratory syncytial virus pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, S.F.; Erickson, S.; Oshman, D.; Hayden, F.

    1985-05-01

    In a study of 30 children with uncomplicated respiratory syncytial virus (RSV) pneumonias, a high incidence of lobar collapse (8/30-26%) was noted. This involved the right upper lobe in seven patients and the left upper lobe in one patient. It is probably attributable to anatomical predispositions, sloughing of necrotic epithelium, and stimulation of mucus production. Lobar collapse should be considered part of the spectrum of RSV pneumonitis.

  19. Efficacy of an intranasal modified live bovine respiratory syncytial virus and temperature-sensitive parainfluenza type 3 virus vaccine in 3-week-old calves experimentally challenged with PI3V.

    Science.gov (United States)

    Vangeel, Ilse; Ioannou, Faye; Riegler, Lutz; Salt, Jeremy S; Harmeyer, Silke S

    2009-01-01

    Two experimental parainfluenza type 3 virus (PI3V) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of an attenuated live vaccine containing modified live bovine respiratory syncytial virus (BRSV) and temperature-sensitive PI3V in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived calves. Nasal shedding of PI3V was highly significantly reduced in vaccinated calves challenged 10 days or 21 days after vaccination. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against PI3V by challenge 66 days post-vaccination. Vaccination also significantly reduced PI3V excretion after challenge in this study. In both studies, clinical signs after challenge were very mild and were not different between vaccinated and control calves.

  20. The epidemiology of respiratory syncytial virus (RSV) infections in ...

    African Journals Online (AJOL)

    South African' or 'children' and 'respiratory syncytial virus' or 'acute respiratory tract infections' as text words were retrieved. We analysed the data on respiratory virus activity from January 1990 to June 1996. Data were obtained from the National ...

  1. Respiratory syncytial virus bronchiolitis in children.

    Science.gov (United States)

    Verger, Judy Trivits; Verger, Emily Elizabeth

    2012-12-01

    Respiratory syncytial virus is a highly infectious virus that commonly causes bronchiolitis and leads to high morbidity and a low, but important, incidence of mortality. Supportive therapy is the foundation of management. Hydration/nutrition and respiratory support are important evidence-based interventions. For children with severe disease, continuous positive airway pressure or mechanical ventilation may be necessary. Ribavirin may be used for treatment of patients with severe disease. Palivizumab provides important ongoing immunoprophylaxis during epidemic months for high-risk infants. Caregiver education and incorporating an explanation of all therapies and anticipatory guidance, including strategies for reducing the risk of infection, are vital. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Mucosal vaccines against respiratory syncytial virus.

    Science.gov (United States)

    Yang, Kejian; Varga, Steven M

    2014-06-01

    Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in infants, young children, immune-compromised and elderly populations worldwide. Natural RSV infection in young children does not elicit long-lasting immunity and individuals remain susceptible to repeated RSV infections throughout life. Because RSV infection is restricted to the respiratory tract, an RSV vaccine should elicit mucosal immunity at upper and lower respiratory tracts in order to most effectively prevent RSV reinfection. Although there is no safe and effective RSV vaccine available, significant progress has been recently made in basic RSV research and vaccine development. This review will discuss recent advances in the identification of a new neutralizing antigenic site within the RSV fusion (F) protein, understanding the importance of mucosal immune responses against RSV infection, and the development of novel mucosal vaccination strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Respiratory syncytial virus and bronchiolitis.

    Science.gov (United States)

    Lemen, R J

    1995-01-01

    Viral bronchiolitis is a common world-wide disease of infants and children resulting in respiratory failure and occasionally death. The major underlying pathophysiology is airway inflammation of peripheral airways and airway hyperresponsiveness to bronchoprovocation. Management is primarily prevention through strict hand washing and avoidance of exposures during respiratory seasons, especially in small infants who have underlying heart or lung disease. Careful supportive therapy, including fluid hydration, good nutrition, and aerosolized bronchodilators, steroids or ribavirin may be helpful. Long term follow-up for these children is important because a significant number will have recurrent episodes of bronchiolitis and wheezing, and many will develop clinical asthma. There's some evidence that long term abnormalities of airway function, perhaps secondary to airway fibrosis, may result from bronchiolitis infections. Avoidance of exposure to passive smoking, cold air and air pollutants is also beneficial to long term recovery from RSV bronchiolitis.

  4. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled ... Infants Multimedia References & Resources Infographic Related Links Unexplained Respiratory Disease Outbreaks Red Book® Online RSV Transmission Recommend ...

  5. Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.

    Science.gov (United States)

    Roymans, Dirk; Alnajjar, Sarhad S; Battles, Michael B; Sitthicharoenchai, Panchan; Furmanova-Hollenstein, Polina; Rigaux, Peter; Berg, Joke Van den; Kwanten, Leen; Ginderen, Marcia Van; Verheyen, Nick; Vranckx, Luc; Jaensch, Steffen; Arnoult, Eric; Voorzaat, Richard; Gallup, Jack M; Larios-Mora, Alejandro; Crabbe, Marjolein; Huntjens, Dymphy; Raboisson, Pierre; Langedijk, Johannes P; Ackermann, Mark R; McLellan, Jason S; Vendeville, Sandrine; Koul, Anil

    2017-08-01

    Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure-activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.Respiratory syncytial virus causes lung infections in children, immunocompromised adults, and in the elderly. Here the authors show that a chemical inhibitor to a viral fusion protein is effective in reducing viral titre and ameliorating infection in rodents and neonatal lambs.

  6. Animal models of respiratory syncytial virus infection.

    Science.gov (United States)

    Taylor, Geraldine

    2017-01-11

    Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore

  7. 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.

    Science.gov (United States)

    Liang, Bo; Munir, Shirin; Amaro-Carambot, Emerito; Surman, Sonja; Mackow, Natalie; Yang, Lijuan; Buchholz, Ursula J; Collins, Peter L; Schaap-Nutt, Anne

    2014-04-01

    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. 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 children. Moreover, this

  8. 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

    Science.gov (United States)

    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

  9. Respiratory Syncytial Virus Bronchiolitis in Children.

    Science.gov (United States)

    Smith, Dustin K; Seales, Sajeewane; Budzik, Carol

    2017-01-15

    Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause of this infection. RSV is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. Patients with RSV bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower respiratory tract symptoms such as increasing cough, wheezing, and increased respiratory effort. In 2014, the American Academy of Pediatrics updated its clinical practice guideline for diagnosis and management of RSV bronchiolitis to minimize unnecessary diagnostic testing and interventions. Bronchiolitis remains a clinical diagnosis, and diagnostic testing is not routinely recommended. Treatment of RSV infection is mainly supportive, and modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and antibiotics are generally not useful. Evidence supports using supplemental oxygen to maintain adequate oxygen saturation; however, continuous pulse oximetry is no longer required. The other mainstay of therapy is intravenous or nasogastric administration of fluids for infants who cannot maintain their hydration status with oral fluid intake. Educating parents on reducing the risk of infection is one of the most important things a physician can do to help prevent RSV infection, especially early in life. Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.

  10. Perinatal Lamb Model of Respiratory Syncytial Virus (RSV Infection

    Directory of Open Access Journals (Sweden)

    Mark R. Ackermann

    2012-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines.

  11. Gold nanorod vaccine for respiratory syncytial virus

    Science.gov (United States)

    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.

  12. Respiratory syncytial virus infection in children.

    Science.gov (United States)

    Dawson-Caswell, Marin; Muncie, Herbert L

    2011-01-15

    Respiratory syncytial virus (RSV) is an RNA virus that causes respiratory tract infections in children. In the North- ern Hemisphere, the peak infection season is November through April. By two years of age, most children will have had an RSV infection. Bronchiolitis, a lower respiratory tract infection, is often caused by RSV. An RSV infection is diagnosed based on patient history and physical examination. Children typically present with cough, coryza, and wheezing. Laboratory testing and chest radiography are not necessary to make the diagnosis. Serious concur- rent bacterial infections are rare. Treatment of an RSV infection is supportive, with particular attention to maintaining hydration and oxygenation. Children younger than 60 days and those with severe symptoms may require hospitalization. Neither antibiotics nor corticosteroids are helpful for bronchiolitis. A bronchodilator trial is appropriate for children with wheezing, but should not be continued unless there is a prompt favorable response. Frequent hand washing and contact isolation may prevent the spread of RSV infections. Children younger than two years at high risk of severe illness, including those born before 35 weeks of gestation and those with chronic lung or cardiac problems, may be candidates for palivizumab prophylaxis for RSV infection during the peak infection season. Most children recover uneventfully with supportive care.

  13. Prophylaxis against respiratory syncytial virus in premature infants

    NARCIS (Netherlands)

    Bont, L; van Vught, AJ; Kimpen, JLL

    1999-01-01

    Postconceptional age was studied in 33 mechanically ventilated preterm infants with respiratory syncytial virus (RSV) bronchiolitis. Preterm infants without chronic lung disease had an increased risk of severe RSV infection until postconceptional age of 44 weeks.

  14. Comparison of single vaccination versus revaccination with a modified-live virus vaccine containing bovine herpesvirus-1, bovine viral diarrhea virus (types 1a and 2a), parainfluenza type 3 virus, and bovine respiratory syncytial virus in the prevention of bovine respiratory disease in cattle.

    Science.gov (United States)

    Step, Douglas L; Krehbiel, Clinton R; Burciaga-Robles, Luis O; Holland, Ben P; Fulton, Robert W; Confer, Anthony W; Bechtol, David T; Brister, David L; Hutcheson, John P; Newcomb, Harold L

    2009-09-01

    Objective-To compare effects of administration of a modified-live respiratory virus vaccine once with administration of the same vaccine twice on the health and performance of cattle. Design-Randomized, controlled trial. Animals-612 mixed-breed male cattle with unknown health histories. Procedures-Cattle were randomly assigned to 1 of 2 treatment groups (single vaccination treatment group [SVAC group] vs revaccination treatment group [REVAC group]) during the preconditioning phase of production. All cattle were given a modified-live respiratory virus vaccine. Eleven days later, REVAC group cattle received a second injection of the same vaccine. During the finishing phase of production, cattle from each treatment group were either vaccinated a third time with the modified-live respiratory virus vaccine or given no vaccine. Health observations were performed daily. Blood and performance variables were measured throughout the experiment. Results-During preconditioning, no significant differences were observed in performance or antibody production between groups. Morbidity rate from bovine respiratory disease was lower for SVAC group cattle; however, days to first treatment for bovine respiratory disease were not different between groups. No significant differences in body weights, daily gains, or dry-matter intake between groups were observed during the finishing phase. Revaccination treatment group cattle had improved feed efficiency regardless of vaccination protocol in the finishing phase. Conclusions and Clinical Relevance-Vaccination once with a modified-live respiratory virus vaccine was as efficacious as vaccination twice in the prevention of bovine respiratory disease of high-risk cattle, although feed efficiency was improved in REVAC group cattle during the finishing period.

  15. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  16. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  17. Seasonal variation of maternally derived respiratory syncytial virus antibodies and association with infant hospitalizations for respiratory syncytial virus

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2009-01-01

    This study used 459 prospectively sampled cord blood samples to examine the association between maternally derived respiratory syncytial virus (RSV)-neutralizing antibodies and the RSV hospitalization season in Denmark. We found a clear temporal association and suggest that RSV...

  18. Human Respiratory Syncytial Virus: Infection and Pathology.

    Science.gov (United States)

    Bohmwald, Karen; Espinoza, Janyra A; Rey-Jurado, Emma; Gómez, Roberto S; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2016-08-01

    The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Respiratory syncytial virus disease: prevention and treatment.

    Science.gov (United States)

    Chu, Helen Y; Englund, Janet A

    2013-01-01

    Respiratory syncytial virus (RSV) is one of the most clinically important viruses infecting young children, the elderly, and the immunocompromised. Over the past decade, the most significant advance in the prevention of RSV disease has been the development of high-titered antibody products. Infection control is the only other strategy to prevent RSV disease. A humanized monoclonal antibody directed against the fusion (F) protein palivizumab, (Synagis®, MedImmune, Inc., Gaithersburg, MD), is given routinely on a monthly basis to premature infants and young children less than 24 months of age with underlying medical problems including prematurity, chronic lung disease, or cardiac disease to prevent RSV disease and hospitalization. Other products utilizing polyclonal or monoclonal antibodies or antibody fragments against the F protein have been developed and some already tested in patient populations. The only licensed antiviral treatment available today is ribavirin, a guanosine analogue generally administered as a small particle aerosol to immunocompromised patients with lower respiratory tract disease due to RSV. This drug has also been utilized in oral and intravenous forms, again mainly in immunocompromised patients. Promising new antiviral agents under development by multiple pharmaceutical and biotechnology companies include small molecule fusion inhibitors, attachment inhibitors, inhibitors of RNA synthesis, and small interfering RNA particles (siRNA).

  20. Type-specific serologic diagnosis of respiratory syncytial virus infection, based on a synthetic peptide of the attachment protein G

    NARCIS (Netherlands)

    Langedijk, J.P.M.; Middel, W.G.J.; Schaaper, W.M.M.; Meloen, R.H.; Kramps, J.A.; Brandenburg, A.H.; Oirschot, van J.T.

    1996-01-01

    Peptides deduced from the central hydrophobic region (residues 158-189) of the G protein of bovine and ovine respiratory syncytial virus (RSV) and of human RSV subtypes A and B were synthesized. These peptides were used to develop ELISAs to measure specifically antibodies against these types and

  1. Evaluation of IgG antibodies against Respiratory Syncytial Virus ...

    African Journals Online (AJOL)

    Evaluation of IgG antibodies against Respiratory Syncytial Virus (RSV), and associated risk factors for severe respiratory tract infections in pre- school children in ... Conclusions: We report a high level of exposure to RSV in infancy and early childhood among children from a representative population in a major central ...

  2. Mechanisms of respiratory syncytial virus specific T cell activation

    NARCIS (Netherlands)

    Kruijsen, D.

    2011-01-01

    Respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections (LRTI) in infants, elderly people and immune compromised individuals. Moreover, RSV causes repeated symptomatic re-infections in healthy individuals, which is presumed to be due to ineffective

  3. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  4. Viral and Bacterial Pathogens in Bovine Respiratory Disease in Finland

    Directory of Open Access Journals (Sweden)

    Soveri T

    2004-12-01

    Full Text Available Pathogens causing bovine respiratory tract disease in Finland were investigated. Eighteen cattle herds with bovine respiratory disease were included. Five diseased calves from each farm were chosen for closer examination and tracheobronchial lavage. Blood samples were taken from the calves at the time of the investigation and from 86 calves 3–4 weeks later. In addition, 6–10 blood samples from animals of different ages were collected from each herd, resulting in 169 samples. Serum samples were tested for antibodies to bovine parainfluenza virus-3 (PIV-3, bovine respiratory syncytial virus (BRSV, bovine coronavirus (BCV, bovine adenovirus-3 (BAV-3 and bovine adenovirus-7 (BAV-7. About one third of the samples were also tested for antibodies to bovine virus diarrhoea virus (BVDV with negative results. Bacteria were cultured from lavage fluid and in vitro susceptibility to selected antimicrobials was tested. According to serological findings, PIV-3, BAV-7, BAV-3, BCV and BRSV are common pathogens in Finnish cattle with respiratory problems. A titre rise especially for BAV-7 and BAV-3, the dual growth of Mycoplasma dispar and Pasteurella multocida, were typical findings in diseased calves. Pasteurella sp. strains showed no resistance to tested antimicrobials. Mycoplasma bovis and Mannheimia haemolytica were not found.

  5. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    OpenAIRE

    Kneijber, M.C.J.; van Heerde, M; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conven...

  6. Comparison of methods for laboratory diagnosis of respiratory syncytial virus

    OpenAIRE

    Maria Cristina Arcangeletti; Silvia Preti; Maria del Pilar Esteban; Emanuel Merep Djouvoup; Valeria Albonetti; Giuseppe Dettori; Carlo Chezzi

    2010-01-01

    Respiratory syncytial virus (RSV) still remains the main agent of lower respiratory tract infections in infants and young children, causing bronchiolitis and/or pneumonia leading to hospitalization and even to death in high-risk patients, such as premature babies. Its great impact on human health supports the need for rapid diagnostic methods in order to control and prevent the infection spread. In this study 63 samples from the respiratory tract were subjected to virological investigations u...

  7. Respiratory syncytial virus: current and emerging treatment options

    OpenAIRE

    Turner TL; Kopp BT; Paul G; Landgrave LC; Hayes D Jr; Thompson R

    2014-01-01

    Tiffany L Turner,1 Benjamin T Kopp,1 Grace Paul,1 Lindsay C Landgrave,2 Don Hayes Jr,1 Rohan Thompson11Department of Pediatrics, Ohio State University College of Medicine, 2Clinical Pharmacy, Nationwide Children's Hospital, Columbus, OH, USAAbstract: Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in ...

  8. Challenges and Opportunities in Developing Respiratory Syncytial Virus Therapeutics

    NARCIS (Netherlands)

    Simoes, Eric A. F.; DeVincenzo, John P.; Boeckh, Michael; Bont, LJ; Crowe, James E.; Griffiths, Paul; Hayden, Frederick G.; Hodinka, Richard L.; Smyth, Rosalind L.; Spencer, Keith; Thirstrup, Steffen; Walsh, Edward E.; Whitley, Richard J.

    2015-01-01

    Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial

  9. Production of interferon in respiratory syncytial virus bronchiolitis.

    OpenAIRE

    Isaacs, D

    1989-01-01

    Production of interferon alfa in vitro was significantly reduced during acute respiratory syncytial virus bronchiolitis but subsequently returned to normal. Nasopharyngeal and endotracheal interferon alfa were detected intermittently and in low concentrations. The degree of impairment of in vitro production and poor in vivo production of interferon alfa suggest the need for a therapeutic trial of nebulised or systemic interferon in acute bronchiolitis.

  10. Respiratory Syncytial Virus Associated Myocarditis Requiring Venoarterial Extracorporeal Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    Anamaria Milas

    2017-01-01

    Full Text Available Severe fulminant myocarditis causing cardiogenic shock can be a rapidly progressing, life threatening condition. Respiratory syncytial virus (RSV is a very rare infectious culprit infrequently described in medical literature as a cause of myocarditis, particularly in adults. We present a case of acute fulminant myocarditis in a patient with PCR positive RSV infection requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO.

  11. Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis.

    NARCIS (Netherlands)

    Boogaard, R.; Hulsmann, A.R.; Veen, L. van; Vaessen-Verberne, A.A.; Yap, Y.N.; Sprij, A.J.; Brinkhorst, G.; Sibbles, B.; Hendriks, T.; Feith, S.W.; Lincke, C.R.; Brandsma, A.E.; Brand, P.L.P.; Hop, W.C.J.; Hoog, M. de; Merkus, P.J.F.M.

    2007-01-01

    BACKGROUND: Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in

  12. Influenza- and respiratory syncytial virus-associated mortality and hospitalisations

    NARCIS (Netherlands)

    Jansen, A G S C; Sanders, E A M; Hoes, A W; van Loon, A M; Hak, E

    2007-01-01

    The aim of the current study was to estimate influenza- and respiratory syncytial virus (RSV)-associated mortality and hospitalisations, especially the influenza-associated burden among low-risk individuals < or =65 yrs old, not yet recommended for influenza vaccination in many European countries.

  13. Influenza- and respiratory syncytial virus-associated adult mortality ...

    African Journals Online (AJOL)

    Background. Influenza and respiratory syncytial virus (RSV) infections cause seasonal excess mortality and hospitalisation in adults (particularly the elderly) in high-income countries. Little information exists on the impact of these infections on adults in Africa. Objectives. To estimate influenza- and RSV-related adult mortality ...

  14. Wheeze after Hospitalization for Respiratory Syncytial Virus Infection in Children

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob; Breindahl, Morten

    2017-01-01

    Introduction Prior studies found associations between respiratory syncytial virus (RSV) infection, wheezing, and asthma. The present study aimed to examine the risk of wheezing after RSV, by the history of wheezing. Methods We included 39 children hospitalized for RSV infection (cases) and 23...

  15. In vivo inhibition of respiratory syncytial virus by ribavirin

    Energy Technology Data Exchange (ETDEWEB)

    Hruska, J.F.; Morrow, P.E.; Suffin, S.C.; Douglas, R.G. Jr.

    1982-01-01

    Ribavirin reduced the amount of respiratory syncytial virus in nasal turbinates and lung tissues of experimentally infected cotton rats by over 90%. An effect was seen when the drug was given either intraperitoneally or by aerosol; however, the antiviral effect was achieved at much lower doses when delivered by the aerosol route. No animal deaths due to the drug were seen.

  16. Respiratory syncytial virus : immunology and immunopathogenesis

    NARCIS (Netherlands)

    Kimpen, Jan

    1993-01-01

    Respiratoir syncytiëel virus (RSV) is de voornaamste verwekker van ernstige bronchiolitis bij zuigelingen. De infectie wordt gekenmerkt door een algemene ontsteking van de bronchiolen,resulterend in een klinisch beeld van ademnood, piepen,en hyperinflatie van de longen. Alhoewel RSV op zich een

  17. Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections.

    Science.gov (United States)

    Yoshida, Lay-Myint; Suzuki, Motoi; Nguyen, Hien Anh; Le, Minh Nhat; Dinh Vu, Thiem; Yoshino, Hiroshi; Schmidt, Wolf-Peter; Nguyen, Thi Thuy Ai; Le, Huu Tho; Morimoto, Konosuke; Moriuchi, Hiroyuki; Dang, Duc Anh; Ariyoshi, Koya

    2013-08-01

    Comprehensive population-based data on the role of respiratory viruses in the development of lower respiratory tract infections (LRTIs) remain unclear. We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam. Population-based prospective surveillance and a case-control study of hospitalised paediatric patients with acute respiratory infection (ARI) were conducted from April 2007 through to March 2010. Healthy controls were randomly recruited from the same community. Nasopharyngeal samples were collected and tested for 13 respiratory viruses using multiplex PCRs. 1992 hospitalised ARI episodes, including 397 (19.9%) with LRTIs, were enrolled. Incidence of hospitalised LRTIs among children aged respiratory syncytial virus (20.1%) and influenza A virus (12.0%) were the most common and 9.5% had multiple-viral infections. Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs. Respiratory syncytial virus further increased the risk, when co-infected with human rhinovirus, human metapneumovirus and parainfluenza virus-3 but not with influenza A virus. The case-control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus. Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam.

  18. Reye's syndrome associated with respiratory syncytial virus infection.

    Science.gov (United States)

    Griffin, N; Keeling, J W; Tomlinson, A H

    1979-01-01

    An upper respiratory tract infection in a 22-month-old boy was followed by rapid loss of consciousness, hypoglycaemia, uraemia, and death. Necropsy examination showed fatty change of liver and kidneys, severe cerebral oedema, bronchiolitis, and endocardial fibroelastosis affecting the left ventricle. Immunofluorescence staining showed infection with respiratory syncytial virus (RSV). The clinical and pathological findings were those of Reye's syndrome, not previously reported accompanying RSV infection. Images Figure PMID:420528

  19. Spread of bovine syncytial virus in a dairy herd over a two year period.

    Science.gov (United States)

    Lucas, M H; Roberts, D H; Parker, B N; Wibberley, G

    1986-03-01

    During a two year period the spread of bovine syncytial virus was monitored in a closed herd of 50 to 100 milking cows. Out of a nucleus of 49 nonpregnant and pregnant heifers, six were found to be infected with bovine syncytial virus. Virus was detected only in the progeny of infected cows and not in the progeny of uninfected animals. Nineteen progeny of the bovine syncytial virus infected cows were studied in detail and virus was isolated from only four. Horizontal spread of the virus did not occur.

  20. [Respiratory syncytial virus infection and asthma].

    Science.gov (United States)

    Martín Mateos, M A

    2001-01-01

    Presentation of bronchial asthma, in the years following the first outbreak of bronchiolitis due to respiratory syncytial virus (RSV) was first described by McIntosh, who postulated a common pathogenesis that was confirmed by the greater frequency (50%) of wheezing bronchiolitis and asthma during the more than 5 year follow up of these children. More recently, Hibbert and Schroechkenstein have again confirmed this phenomenon. These authors report that the percentage of asthma was increased by up to 71% in a group of children who contracted bronchiolitis during the first year of life and who were closely followed-up for 5 years after the outbreak. Other authors report figures between 25% and 57%. Stein et al. followed-up 888 children with RSV bronchiolitis until the age of 13 years and observed that at the age of 3-5 years 69% had asthma, at 4-5 years 55% did so and at 6-8 years 31% were asthmatic. In our experience of children who developed RSV bronchiolitis before the age of 6 months, 58 of 75 developed infantile asthma in following 3 years. Seventeen infants were aged more than 6 months at onset of bronchiolitis and of these 5 had bronchiolitis. We carried out a prospective study of 50 children aged 3-7 months with RSV bronchiolitis from December 1997 to February 1998. Follow-up was until the year 2000. Of these children, 22 (44%) had asthma and the remaining 28 (56%) had isolated episodes of cough and wheezing, which did not fulfill the criteria for asthma. Of the 22 children with asthma, all presented elevated total IgE by the second year of follow-up but only one of the children presented hypersensitivity to egg. The breathing difficulties that appeared in the initial outbreak of bronchiolitis is well explained by the cytopathic effect of the virus on the airways of infants. RSV virus produces inflammation of the bronchial mucosa, the effects of which may persist for 6-7 weeks, even after recovery from the first episode. The damaged and denuded epithelium

  1. Equal virulence of rhinovirus and respiratory syncytial virus in infants hospitalized for lower respiratory tract infection

    NARCIS (Netherlands)

    van Leeuwen, J.C.; Goossens, L.K.; Hendrix, R.; van der Palen, Jacobus Adrianus Maria; Lusthusz, A.; Thio, B.J.

    2012-01-01

    Respiratory syncytial virus (RSV) and rhinovirus (RV) are predominant viruses associated with lower respiratory tract infection in infants. We compared the symptoms of lower respiratory tract infection caused by RSV and RV in hospitalized infants. RV showed the same symptoms as RSV, so on clinical

  2. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    Directory of Open Access Journals (Sweden)

    Timothy A. Reinhardt

    2012-12-01

    Full Text Available 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 nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8. This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants.

  3. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    Science.gov (United States)

    Sacco, Randy E.; McGill, Jodi L.; Palmer, Mitchell V.; Lippolis, John D.; Reinhardt, Timothy A.; Nonnecke, Brian J.

    2012-01-01

    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 nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8). This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants. PMID:23342375

  4. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity

    NARCIS (Netherlands)

    R.S. Tang (Roderick); J.H. Schickli (Jeanne); M. MacPhail (Mia); F. Fernandes (Fiona); L. Bicha (Leenas); J. Spaete (Joshua); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); R. Spaete (Richard); A.A. Haller (Aurelia)

    2003-01-01

    textabstractA live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory

  5. Structural basis of respiratory syncytial virus neutralization by motavizumab

    Energy Technology Data Exchange (ETDEWEB)

    McLellan, Jason S.; Chen, Man; Kim, Albert; Yang, Yongping; Graham, Barney S.; Kwong, Peter D. (NIH)

    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.

  6. Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy

    NARCIS (Netherlands)

    Achten, Niek B.; Wu, Pingsheng; Bont, Louis; Blanken, Maarten O; Gebretsadik, Tebeb; Chappell, James D; Wang, Li; Yu, Chang; Larkin, Emma K; Carroll, Kecia N; Anderson, Larry J; Moore, Martin L; Sloan, Chantel D; Hartert, Tina V

    2017-01-01

    Background.: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. Methods.: To study viral

  7. Lower respiratory tract infection caused by respiratory syncytial virus : current management and new therapeutics

    NARCIS (Netherlands)

    Mazur, Natalie; Martinon-Torres, Federico; Baraldi, Eugenio; Fauroux, Brigitte; Greenough, Anne; Heikkinen, Terho; Manzoni, Paolo; Mejias, Asuncion; Nair, Harish; Papadopoulos, Nikolaos G.; Polack, Fernando P.; Ramilo, Octavio; Sharland, Mike; Stein, Renato; Madhi, Shabir A.; Bont, Louis

    2015-01-01

    Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and

  8. Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection

    NARCIS (Netherlands)

    Bont, L; Steijn, M; van Aalderen, WMC; Brus, F; Draaisma, JMT; Van Diemen-Steenvoorde, RAAM; Pekelharing-Berghuis, M; Kimpen, JLL

    Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of

  9. BIOLOGY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS: A ...

    African Journals Online (AJOL)

    DR. AMINU

    cause of lower respiratory tract infection during infancy and early childhood worldwide. ... respiratory tract disease requiring hospitalization (Tripp, 2004). The magnitude and intensity of infection and the host response to RSV infection determine the severity and intensity of the .... paramyxoviruses in structure and function.

  10. Atypical Presentations of Respiratory Syncytial Virus Infection; Case series

    Directory of Open Access Journals (Sweden)

    Nawal Al-Maskari

    2016-02-01

    Full Text Available The respiratory syncytial virus (RSV usually causes a lower respiratory tract infection in affected patients. RSV has also been infrequently linked to extrapulmonary diseases in children. We report four children who had unusually severe clinical manifestations of RSV infections requiring critical care admission. These patients presented to the Royal Hospital, Muscat, Oman, in December 2013 with acute necrotising encephalopathy (ANE, acute fulminant hepatic failure with encephalopathy, pneumatoceles and croup. A unique presentation of ANE has not previously been reported in association with an RSV infection. All patients had a positive outcome and recovered fully with supportive management.

  11. Serological and genetic characterisation of bovine respiratory syncytial virus (BRSV) indicates that Danish isolates belong to the intermediate subgroup: no evidence of a selective effect on the variability of G protein nucleotide sequence by prior cell culture adaption and passages in cell culture

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Uttenthal, Åse; Arctander, P.

    1998-01-01

    Danish isolates of bovine respiratory syncytial virus (BRSV) were characterised by nucleotide sequencing of the G glycoprotein and by their reactivity with a panel of monoclonal antibodies (MAbs). Among the six Danish isolates, the overall sequence divergence ranged between 0 and 3...... part of the G gene of additional 11 field BRSV viruses, processed directly from lung samples without prior adaption to cell culture growth. revealed sequence variabilities in the range obtained with the propagated virus. In addition, several passages in cell culture and in calves had no major impact...... on the nucleotide sequence of the G protein. These findings indicated that the previously established variabilities of the G protein of RS virus isolates were not attributable to mutations induced during the propagation of the virus. The reactivity of the Danish isolates with G protein-specific MAbs were similar...

  12. Respiratory syncytial virus: current and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Turner TL

    2014-04-01

    Full Text Available Tiffany L Turner,1 Benjamin T Kopp,1 Grace Paul,1 Lindsay C Landgrave,2 Don Hayes Jr,1 Rohan Thompson11Department of Pediatrics, Ohio State University College of Medicine, 2Clinical Pharmacy, Nationwide Children's Hospital, Columbus, OH, USAAbstract: Respiratory syncytial virus (RSV is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis® has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.Keywords: bronchiolitis, lower respiratory tract infection, respiratory syncytial virus, probiotics, vitamin D

  13. Radiological features of lower respiratory infection by respiratory syncytial virus in infants and young children

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Sun; Kim, In One; Yeon, Kyung Mo; Jang, Seong Hee; Lee, Hoan Jong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1992-07-15

    Respiratory syncytial virus is the most common cause of lower respiratory infection (bronchiolitis and pneumonia) of infancy and early childhood. We analyzed clinical and radiological features of 76 patients with lower respiratory infections by respiratory syncytial virus, which were diagnosed by indirect immunofluorescent test or culture of nasal aspirate in Hep-2-cell monolayer, during the period of January- December, 1991. There were peaks of incidences in March-May and November- December, accounting for 87% of eases. Sixty-two cases (82%) were under 1 year of age. Fifty cases (66%) had underlying diseases. Major radiographical findings were overaeration (83%), parahilar peribronchial infiltrates (67%), segmental or subsegmental atelectasis (32%), and segmental or lobar consolidation (16%). In 15 cases (20%), overaeration was the only radiological findings. There was no evidence of pleural effusion or lymph node enlargement in all cases. By considering clinical features (symptoms, age, underlying diseases, epidemic seasons) in addition to the radiological findings, radiologists would be familiar with lower respiratory infection by respiratory syncytial virus. Air space consolidation, which is generally thought to represent bacterial pneumonia, is also observed not infrequently in respiratory syncytial virus infection.

  14. Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis.

    Science.gov (United States)

    Pickles, Raymond J; DeVincenzo, John P

    2015-01-01

    Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar airways, ie bronchiolitis. The most common aetological agents causing bronchiolitis in young children are the respiratory viruses, and of the commonly encountered respiratory viruses, respiratory syncytial virus (RSV) has a propensity for causing bronchiolitis. Indeed, RSV bronchiolitis remains the major reason why previously healthy infants are admitted to hospital. Why RSV infection is such a predominant cause of bronchiolitis is the subject of this review. By reviewing the available histopathology of RSV bronchiolitis, both in humans and relevant animal models, we identify hallmark features of RSV infection of the distal airways and focus attention on the consequences of columnar cell cytopathology occurring in the bronchioles, which directly impacts the development of bronchiolar obstruction, inflammation and disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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.

  16. Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

    NARCIS (Netherlands)

    Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.

    2004-01-01

    Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,

  17. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus

    NARCIS (Netherlands)

    van Woensel, JBM; van Aalderen, WMC; de Weerd, W; Jansen, NJG; van Gestel, JPJ; Markhorst, DG; van Vught, AJ; Bos, AP; Kimpen, JLL

    Background: A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI). Methods: In a multicentre randomised controlled trial patients were randomised to receive either

  18. Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease

    NARCIS (Netherlands)

    Kneyber, MCJ; van Oud-Alblas, HB; van Vliet, M; Uiterwaal, CSPM; Kimpen, JLL; van Vught, AJ

    Objective: To identify demographic, clinical, and laboratory variables predictive for a concurrent bacterial pulmonary infection in ventilated infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) and investigate antimicrobial drug use. Design and setting:

  19. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  20. Immunoprophylaxis of bovine respiratory syndrome

    Directory of Open Access Journals (Sweden)

    Rogan Dragan

    2010-01-01

    Full Text Available Bovine Respiratory Syndrome (BRS is a multifactorial disease caused by the interaction of infective agents, the environment and the individual immunological response of animals in the herd. Despite five decades of research on BRS, no clear understanding of how environmental factors influence pathogenic outcomes of the disease has been defined. As such, the development of immunoprophylaxis and vaccine programmes to prevent outbreaks of BRS in cattle has not been successful. The current paper discusses vaccination programmes for all categories of cattle and presents a review of existing vaccines being used for immunoprophylaxis of respiratory syndrome in cattle and discusses the advantages and disadvantages of the currently used vaccines and vaccination programmes. Lastly, a discussion detailing the design of future perfect vaccines is presented.

  1. DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis

    NARCIS (Netherlands)

    P.J.F.M. Merkus (Peter); M. de Hoog (Matthijs); R. van Gent; J.C. de Jongste (Johan)

    2001-01-01

    textabstractRespiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The

  2. Streptococcus pneumoniae enhances human respiratory syncytial virus infection in vitro and in vivo

    NARCIS (Netherlands)

    D.T. Nguyen (Tien); R.P.L. Louwen (Rogier); Elberse, K. (Karin); G. van Amerongen (Geert); S. Yüksel (Selma); A. Luijendijk (Ad); A.D.M.E. Osterhaus (Albert); W.P. Duprex (William Paul); R.L. de Swart (Rik)

    2015-01-01

    textabstractHuman respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants

  3. Variation of respiratory syncytial virus and the relation with meteorological factors in different winter seasons.

    NARCIS (Netherlands)

    Meerhoff, T.J.; Paget, W.J.; Kimpen, J.L.; Schellevis, F.

    2009-01-01

    Background: Respiratory syncytial virus (RSV) is the most important viral agent causing severe respiratory disease in infants and children. In temperate climates, RSV activity typically peaks during winter. We have described the seasonal variation in RSV activity and investigated which

  4. Validation of a pediatric caregiver diary to measure symptoms of postacute respiratory syncytial virus bronchiolitis

    DEFF Research Database (Denmark)

    Santanello, Nancy C; Norquist, Josephine M; Nelsen, Linda M

    2005-01-01

    Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity...

  5. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus

    NARCIS (Netherlands)

    Gaunt, Eleanor R.; Jansen, Rogier R.; Poovorawan, Yong; Templeton, Kate E.; Toms, Geoffrey L.; Simmonds, Peter

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  6. Molecular Epidemiology and Evolution of Human Respiratory Syncytial Virus and Human Metapneumovirus

    NARCIS (Netherlands)

    Gaunt, E.R.; Jansen, R.R.; Poovorawan, Y.; Templeton, K.E.; Toms, G.L.; Simmonds, P.

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  7. Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis.

    Science.gov (United States)

    Heath, Paul T; Culley, Fiona J; Jones, Christine E; Kampmann, Beate; Le Doare, Kirsty; Nunes, Marta C; Sadarangani, Manish; Chaudhry, Zain; Baker, Carol J; Openshaw, Peter J M

    2017-07-01

    Group B streptococcus and respiratory syncytial virus are leading causes of infant morbidity and mortality worldwide. No licensed vaccines are available for either disease, but vaccines for both are under development. Severe respiratory syncytial virus disease can be prevented by passively administered antibody. The presence of maternal IgG antibody specific to respiratory syncytial virus is associated with reduced prevalence and severity of respiratory syncytial virus disease in the first few weeks of life, whereas maternal serotype-specific anticapsular antibody is associated with protection against both early-onset and late-onset group B streptococcus disease. Therefore, vaccination in pregnancy might protect infants against both diseases. This report describes what is known about immune protection against group B streptococcus and respiratory syncytial virus, identifies knowledge gaps regarding the immunobiology of both diseases, and aims to prioritise research directions in maternal immunisation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Respiratory Syncytial Virus and Other Noninfluenza Respiratory Viruses in Older Adults.

    Science.gov (United States)

    Kodama, Fumihiro; Nace, David A; Jump, Robin L P

    2017-12-01

    Respiratory viral infections may cause serious complications for older adults, including residents of long-term care facilities (LTCFs). Although influenza is the most common cause of viral respiratory infections among older adults, several other respiratory viruses also cause significant morbidity and mortality, most notably respiratory syncytial virus. Other noninfluenza respiratory viral pathogens include human metapneumovirus, parainfluenza virus, rhinovirus, coronavirus, and adenovirus. All of these may cause outbreaks among LTCF residents. Recently developed rapid diagnostic molecular tests may clarify the epidemiology of these viruses and have potential, through early identification, to limit the severity of outbreaks among older adults living in LTCFs. Published by Elsevier Inc.

  9. Overview of respiratory syncytial virus disease in young children

    Directory of Open Access Journals (Sweden)

    Hoopes JM

    2012-07-01

    Full Text Available J Michael Hoopes1, Veena R Kumar21Medical Information, 2Medical and Scientific Affairs, MedImmune, LLC, Gaithersburg, MD, USAAbstract: Respiratory tract illnesses associated with respiratory syncytial virus (RSV were first reported more than 160 years ago and gained acceptance as a major respiratory pathogen in the late 1950s. Annual epidemics show a seasonal pattern typically beginning in the late fall and ending in early spring, averaging 5 months in length, and varying in time of onset, offset, and duration depending on geographic location. Manifestations of RSV illness primarily involve the upper respiratory tract but can spread to the lower airways and lead to bronchiolitis and/or pneumonia. Initial infection occurs in approximately two-thirds of children during the first year of life; nearly all children are infected at least once by 2 years of age. Reinfection is common throughout life, but initial illness during infancy generally presents with the most severe symptoms. Medical risk conditions that consistently predispose young children to serious lower respiratory tract infection (LRTI include congenital heart disease, chronic lung disease, and premature birth. Serious LRTI due to RSV is the leading cause of hospitalization in infants and young children worldwide and annual mean hospital expenses have been estimated to exceed 1 billion dollars in the United States. Young children incur more inpatient and outpatient visits for RSV LRTI than for influenza. RSV has a greater impact than influenza on hospitalization in infants with respect to length of stay, severity/course of disease, and resultant needs for ancillary treatments. Unlike many other childhood illnesses, a vaccine is not currently available for preventing RSV disease.Keywords: bronchopulmonary dysplasia, infants, hospitalization, prematurity, respiratory syncytial virus

  10. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...... subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut...

  11. Replication of respiratory syncytial virus in lungs of immunodeficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Wyde, P.R.; Sun, C.S.; Knight, V.

    1983-08-01

    Respiratory syncytial virus was frequently isolated during a 10-day test period from the lungs of 4- to 6-week-old immunodeficient nude (nu/nu) mice and from gamma-irradiated C3H mice inoculated intranasally with this virus, but not from similar aged and comparably inoculated normal littermates of these mice. Virus isolation rates and levels of virus in lungs in both groups of immunodeficient mice were similar. No extrapulmonary dissemination of virus was observed in any test group of mice.

  12. Nosocomial infections by respiratory syncytial virus in children

    Directory of Open Access Journals (Sweden)

    Maren Karina Machado Echeverría

    2017-01-01

    Full Text Available Introduction: Acute lower respiratory infections cause high morbidity and mortality in children. Respiratory syncytial virus (RSV is the most prevalent agent. Some viruses cause serious nosocomial infections. In Uruguay, there is no knowledge about the morbidity and mortality of nosocomial infections by RSV. Objective: To determine the prevalence and characteristics of RSV nosocomial infections. Methodology: A descriptive study of acute lower respiratory infections caused by RSV in patients younger than two years, between 1/1/2005 and 31/12/2008 at the Hospital Pediátrico del Centro Hospitalario Pereira Rossell, was made. Results: Were identified 59 patients who represented an annual rate lower than 2/1000 discharges. The monthly distribution of cases was similar to the respiratory infections. No outbreaks were reported. The age of the patients had an average of 8.9 months, 39 were younger than one year, 23 had one or more risk factors for severe disease. Six patients required admission to intensive care unit, all required invasive ventilation, 3 died, none had chronic respiratory failure following the RSV nosocomial infection. Conclusions: During the study period, the RSV nosocomial infections showed a low prevalence, despite it highly contagiousness. They mainly affected young children, carriers of risk factors for severe ALRI. Their evolution was similar to that reported for RSV respiratory infections community acquired. It is important to maintain standards for the control of nosocomial infections, to prevent nosocomial transmission of RSV and prevent the onset of severe disease in hospitalized patients.

  13. Respiratory Syncytial Virus: Current Progress in Vaccine Development

    Science.gov (United States)

    Rudraraju, Rajeev; Jones, Bart G.; Sealy, Robert; Surman, Sherri L.; Hurwitz, Julia L.

    2013-01-01

    Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding that re-infection risks are inversely associated with neutralizing antibody titers suggest that immune responses generated toward a first RSV exposure can significantly reduce morbidity and mortality throughout life. For more than half a century, researchers have endeavored to design a vaccine for RSV that can mimic or improve upon natural protective immunity without adverse events. The virus is herein described together with the hurdles that must be overcome to develop a vaccine and some current vaccine development approaches. PMID:23385470

  14. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.

    Science.gov (United States)

    Schmidt, Alexander C; Wenzke, Daniel R; McAuliffe, Josephine M; St Claire, Marisa; Elkins, William R; Murphy, Brian R; Collins, Peter L

    2002-02-01

    Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

  15. Influenza and respiratory syncytial virus infections in British Hajj pilgrims

    Science.gov (United States)

    Rashid, H; Shafi, S; Booy, R; El Bashir, H; Ali, K; Zambon, MC; Memish, ZA; Ellis, J; Coen, PG; Haworth, E

    2008-01-01

    Viral respiratory infections including influenza and respiratory syncytial virus (RSV) have been reported during the Hajj among international pilgrims. To help establish the burden of these infections at the Hajj, we set up a study to confirm these diagnoses in symptomatic British pilgrims who attended the 2005 Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were invited to participate; after taking medical history, nasal swabs were collected for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus-positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had recently had a flu immunisation. Influenza was more common in those who gave a history of contact with a pilgrim with a respiratory illness than those who did not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms that influenza and RSV cause acute respiratory infections in British Hajj pilgrims. Continuing surveillance and a programme of interventions to contain the spread of infection are needed at the Hajj, particularly when the world is preparing for an influenza pandemic. PMID:22460211

  16. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

    Directory of Open Access Journals (Sweden)

    Laurel J Gershwin

    Full Text Available Bovine respiratory disease complex (BRDC is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus, which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

  17. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

    Science.gov (United States)

    Gershwin, Laurel J; Van Eenennaam, Alison L; Anderson, Mark L; McEligot, Heather A; Shao, Matt X; Toaff-Rosenstein, Rachel; Taylor, Jeremy F; Neibergs, Holly L; Womack, James

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

  18. Vaccines against respiratory syncytial virus: The time has finally come.

    Science.gov (United States)

    Graham, Barney S

    2016-06-24

    Respiratory syncytial virus causes a significant public health burden, particularly in very young infants and the frail elderly. The legacy of enhanced RSV disease (ERD) from a whole formalin-inactivated RSV vaccine, and the complex biology of the virus and the neonate have delayed the development of effective vaccines. However, new insights into factors associated with ERD and breakthroughs in understanding the antigenic structure of the fusion (F) glycoprotein have increased optimism that vaccine development is possible. This has led to investment of time and resources by industry, regulatory authorities, governments, and nonprofit organizations to develop the infrastructure needed to make the advanced clinical development of RSV vaccine candidates a reality. Published by Elsevier Ltd.

  19. Increased prevalence of otitis media following respiratory syncytial virus infection.

    Science.gov (United States)

    Kristjánsson, S; Skúladóttir, H E; Sturludóttir, M; Wennergren, G

    2010-06-01

    The aim of this study was to analyse whether, during the 18 months following a respiratory syncytial virus (RSV) infection in infants, there were differences in the prevalence of common infections such as acute otitis media (AOM), compared with controls. We also wanted to see whether passive smoking could be a contributory factor. In a longitudinal study, 33 children who attended the emergency room with an RSV infection (age antibiotics were higher in the RSV group than in the controls (p = 0.009 and p = 0.027 respectively). The number of AOMs and the use of antibiotics correlated, r = 0.8. In the RSV group, one or both parents smoked in 52% compared with 14% in the controls (p antibiotics more frequently during the follow-up period. Furthermore, smoking was far more common among the parents of the RSV group. We speculate that passive smoking could be a contributory factor to the infections noted here.

  20. Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection

    DEFF Research Database (Denmark)

    Kristensen, Kim; Fisker, Niels; Haerskjold, Ann

    2015-01-01

    BACKGROUND AND OBJECTIVE:: Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated...... regression with adjustment for prematurity, asphyxia, birth weight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings, and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery...... infection in children born by acute CS and by elective CS were 1.09 (1.01 - 1.17) and 1.27 (1.19 - 1.36), respectively. The effect of elective CS remained unchanged throughout the first two years of life (p = 0.53), whereas the effect of acute CS was only present in the second year of life (p = 0...

  1. Comparison of methods for laboratory diagnosis of respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Maria Cristina Arcangeletti

    2010-09-01

    Full Text Available Respiratory syncytial virus (RSV still remains the main agent of lower respiratory tract infections in infants and young children, causing bronchiolitis and/or pneumonia leading to hospitalization and even to death in high-risk patients, such as premature babies. Its great impact on human health supports the need for rapid diagnostic methods in order to control and prevent the infection spread. In this study 63 samples from the respiratory tract were subjected to virological investigations usually applied in diagnostic routine: the research of RSV antigens in cells derived from the biological samples by immunofluorescence (IFD, as well as the rapid and the traditional cell culture methods (MR and MT, respectively.A third rapid test, the immunochromatographic assay TRU RSVTM (Meridian, for the research of RSV specific proteins, was applied retrospectively to the same samples stored at -80°C. Among the above considered routine methods, the most reliable for rapid diagnosis of RSV infection in our hands was IFD, which was able to reveal the greatest number of positive samples (54/63 and was therefore considered as the reference technique. The immunochromatographic assay TRU RSVTM identified 39/54 positive samples (72.2%, the bulk of which superposed with those also resulted positive with MR and/or MT (i.e. samples with high viral load. On the other hand, the immunochromatographic test was unable to detect RSV antigens in the majority of samples positive only with IFD (i.e. samples with low viral load.

  2. Respiratory syncytial virus: current and emerging treatment options.

    Science.gov (United States)

    Turner, Tiffany L; Kopp, Benjamin T; Paul, Grace; Landgrave, Lindsay C; Hayes, Don; Thompson, Rohan

    2014-01-01

    Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis(®)) has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.

  3. Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

    NARCIS (Netherlands)

    Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  4. Invasive pneumococcal and meningococcal disease: association with influenza virus and respiratory syncytial virus activity?

    NARCIS (Netherlands)

    Jansen, A. G. S. C.; Sanders, E. A. M.; van der Ende, A.; van Loon, A. M.; Hoes, A. W.; Hak, E.

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  5. G protein variation in respiratory syncytial virus group A does not correlate with clinical severity

    NARCIS (Netherlands)

    A.H. Brandenburg (Afke); H.A. Moll (Henriëtte); E.C.J. Claas (Eric); A.D.M.E. Osterhaus (Albert); R. van Beek (Ruud)

    2000-01-01

    textabstractRespiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by analyzing G protein sequences. Several lineages circulated repeatedly and simultaneously during the respective seasons.

  6. Causal direction between respiratory syncytial virus bronchiolitis and asthma studied in monozygotic twins

    DEFF Research Database (Denmark)

    Poorisrisak, Porntiva; Halkjaer, Liselotte Brydensholt; Thomsen, Simon Francis

    2010-01-01

    Respiratory syncytial virus (RSV) bronchiolitis has been associated with later development of asthma, wheezing, abnormal pulmonary function, and sensitization. Our aim was to determine the differential effect within monozygotic (MZ) twin pairs discordant for severe RSV bronchiolitis in infancy...

  7. The causal direction in the association between respiratory syncytial virus hospitalization and asthma

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob Brunbjerg; Thomsen, Simon Francis

    2009-01-01

    BACKGROUND: Earlier studies have reported an increased risk of asthma after respiratory syncytial virus (RSV) hospitalization. Other studies found that asthmatic disposition and propensity to wheeze increase the risk of RSV hospitalization. OBJECTIVE: The current study examined the causal direction...

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

    DEFF Research Database (Denmark)

    Carbonell-Estrany, Xavier; Simões, Eric A F; Dagan, Ron

    2009-01-01

    OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies...

  9. Increased concordance of severe respiratory syncytial virus infection in identical twins

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Stensballe, Lone Graff; Skytthe, Axel

    2008-01-01

    OBJECTIVE: We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors. METHODS: Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12,346 pairs) born...... in Denmark between 1994 and 2003. Latent-factor models of genetic and environmental effects were fitted to the observed data by using maximal likelihood methods. RESULTS: Identical twins resembled each other significantly more than did fraternal twins for respiratory syncytial virus hospitalization...... (concordance rate: 0.66 vs 0.53), which suggests genetic influences on disease severity. Genetic factors accounted for 16%, family environment for 73%, and nonshared environment for 11% of the individual susceptibility to develop severe respiratory syncytial virus infection. CONCLUSIONS: The severity...

  10. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Flores-Nunez, Alejandro; Goh, Anne

    2008-01-01

    RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus...... (RSV) bronchiolitic respiratory symptoms. OBJECTIVES: To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. METHODS: This was a double-blind study of 3- to 24-month-old children who.......7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. CONCLUSIONS: In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children....

  11. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, H.; Flores-Nunez, A.; Goh, A.

    2008-01-01

    RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus...... (RSV) bronchiolitic respiratory symptoms. OBJECTIVES: To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. METHODS: This was a double-blind study of 3- to 24-month-old children who.......7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. CONCLUSIONS: In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children Udgivelsesdato: 2008/10/15...

  12. Lipopeptide-adjuvanted respiratory syncytial virus virosomes : A safe and immunogenic non-replicating vaccine formulation

    NARCIS (Netherlands)

    Stegmann, Toon; Kamphuis, Tobias; Meijerhof, Tjarko; Goud, Ellen; de Haan, Aalzen; Wilschut, Jan

    2010-01-01

    Respiratory syncytial virus (RSV) causes severe respiratory disease in children and the elderly. There is no registered RSV vaccine. Early experimental non-replicating vaccines have been found to exacerbate RSV symptoms upon infection causing enhanced respiratory disease. Here we show that

  13. Respiratory Syncytial Virus Entry Inhibitors Targeting the F Protein

    Directory of Open Access Journals (Sweden)

    Shibo Jiang

    2013-01-01

    Full Text Available Human respiratory syncytial virus (RSV is the main viral cause of respiratory tract infection in infants as well as some elderly and high-risk adults with chronic pulmonary disease and the severely immunocompromised. So far, no specific anti-RSV therapeutics or effective anti-RSV vaccines have been reported. Only one humanized monoclonal antibody, Palivizumab, has been approved for use in high-risk infants to prevent RSV infection. Ribavirin is the only drug licensed for therapy of RSV infection, but its clinical use is limited by its nonspecific anti-RSV activity, toxic effect, and relatively high cost. Therefore, development of novel effective anti-RSV therapeutics is urgently needed. The RSV envelope glycoprotein F plays an important role in RSV fusion with, and entry into, the host cell and, consequently, serves as an attractive target for developing RSV entry inhibitors. This article reviews advances made in studies of the structure and function of the F protein and the development of RSV entry inhibitors targeting it.

  14. Assessing Uncertainty in A2 Respiratory Syncytial Virus Viral Dynamics

    Directory of Open Access Journals (Sweden)

    Gilberto González-Parra

    2015-01-01

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis and pneumonia in children younger than 1 year of age in the United States. Moreover, RSV is being recognized more often as a significant cause of respiratory illness in older adults. Although RSV has been studied both clinically and in vitro, a quantitative understanding of the infection dynamics is still lacking. In this paper, we study the effect of uncertainty in the main parameters of a viral kinetics model of RSV. We first characterize the RSV replication cycle and extract parameter values by fitting the mathematical model to in vivo data from eight human subjects. We then use Monte Carlo numerical simulations to determine how uncertainty in the parameter values will affect model predictions. We find that uncertainty in the infection rate, eclipse phase duration, and infectious lifespan most affect the predicted dynamics of RSV. This study provides the first estimate of in vivo RSV infection parameters, helping to quantify RSV dynamics. Our assessment of the effect of uncertainty will help guide future experimental design to obtain more precise parameter values.

  15. Adolescent asthma after rhinovirus and respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Ruotsalainen, Marja; Hyvärinen, Mari K; Piippo-Savolainen, Eija; Korppi, Matti

    2013-07-01

    Asthma risk is increased after bronchiolitis in infancy. Recent studies have suggested that the risk may be dependent on the causative virus. The aim of the study was to evaluate the asthma risk in adolescence in subjects hospitalized for rhinovirus or respiratory syncytial virus (RSV) bronchiolitis in infancy. At the median age of 16.5 years, a questionnaire was sent to 96 study subjects hospitalized for bronchiolitis at rhinovirus etiology of bronchiolitis had been studied in serum and respiratory samples obtained on admission in infancy. The occurrence of asthma was compared between former bronchiolitis patients and population controls recruited for this study in adolescence. Doctor-diagnosed asthma was present in 30% of former bronchiolitis patients and in 5% of controls (OR 7.9, 95% CI 3.3-19.3). The respective figures for self-reported asthma were 64% and 11% (OR 14.7, 95% CI 7.2-30.0). Self-reported asthma was more common in the former rhinovirus than RSV patients (83.3% vs. 47.6%, P = 0.023, mixed infections included; 81.3% vs. 50%, P = 0.067, mixed infections excluded). Patients hospitalized for RSV and rhinovirus bronchiolitis at rhinovirus versus non-rhinovirus bronchiolitis. Copyright © 2012 Wiley Periodicals, Inc.

  16. Mechanism of action for respiratory syncytial virus inhibitor RSV604.

    Science.gov (United States)

    Challa, SreeRupa; Scott, Andrew D; Yuzhakov, Olga; Zhou, Ying; Tiong-Yip, Choi Lai; Gao, Ning; Thresher, Jason; Yu, Qin

    2015-02-01

    Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children and other high-risk populations. RSV nucleoprotein (N) is essential for virus assembly and replication as part of the viral ribonucleoprotein (RNP) complex. RSV604 was a putative N inhibitor in phase 2 clinical trials whose molecular mechanism of action (MoA) was not well understood. This study investigated the cell line-dependent potency of RSV604 and demonstrated its direct binding to the N protein in vitro, providing the first evidence of direct target engagement for this class of inhibitors reported to date. The affinity of RSV604 N binding was not affected by RSV604 resistance mutations in the N protein. RSV604 engaged in two different MoAs in HeLa cells, inhibiting both RSV RNA synthesis and the infectivity of released virus. The lack of inhibition of viral RNA synthesis in some cell lines explained the cell-type-dependent potency of the inhibitor. RSV604 did not inhibit viral RNA synthesis in the RSV subgenomic replicon cells or in the cell-free RNP assay, suggesting that it might act prior to viral replication complex formation. RSV604 did not alter N protein localization in the infected cells. Taken together, these results provide new insights leading to an understanding of the MoAs of RSV604 and other similar N inhibitors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. The biennial cycle of respiratory syncytial virus outbreaks in Croatia

    Directory of Open Access Journals (Sweden)

    Drazenovic Vladimir

    2008-01-01

    Full Text Available Abstract The paper analyses the epidemic pattern of respiratory syncytial virus (RSV outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994–2005 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23–25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

  18. Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B.

    Science.gov (United States)

    Kimura, Hirokazu; Nagasawa, Koo; Kimura, Ryusuke; Tsukagoshi, Hiroyuki; Matsushima, Yuki; Fujita, Kiyotaka; Hirano, Eiko; Ishiwada, Naruhiko; Misaki, Takako; Oishi, Kazunori; Kuroda, Makoto; Ryo, Akihide

    2017-08-01

    In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10(-4)substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Down syndrome : A novel risk factor for respiratory syncytial virus bronchiolitis - A prospective birth-cohort study

    NARCIS (Netherlands)

    Bloemers, Beatrijs L. P.; van Furth, Marceline; Weijerman, Michel E.; Gemke, Reinoud J. B. J.; Broers, Chantal J. M.; van den Ende, Kimberly; Kimpen, Jan L. L.; Strengers, Jan L. M.; Bont, Louis J.

    2007-01-01

    OBJECTIVES. Respiratory syncytial virus is the single-most important cause of lower respiratory tract infections in children. Preterm birth and congenital heart disease are known risk factors for severe respiratory syncytial virus infections. Although Down syndrome is associated with a high risk of

  20. The pharmacologic mechanism by which inhaled epinephrine reduces airway obstruction in respiratory syncytial virus-associated bronchiolitis.

    Science.gov (United States)

    Barr, F E; Patel, N R; Newth, C J

    2000-05-01

    Inhaled racemic epinephrine relieves airway obstruction in patients with respiratory syncytial virus bronchiolitis. The contribution of alpha- versus beta-adrenoreceptor stimulation toward this clinical effect is unknown. We describe an infant treated with propranolol for supraventricular tachycardia in whom respiratory syncytial virus bronchiolitis developed. Inhaled racemic epinephrine improved his respiratory symptoms, whereas nebulized albuterol did not.

  1. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Larsen, Hans Henrik; Eugen-Olsen, Jesper

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p infected children required respiratory support. hMPV is present in young.......6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young...

  2. Prevalence of rhinovirus in wheezing children: a comparison with respiratory syncytial virus wheezing.

    Science.gov (United States)

    Sun, Huiquan; Sun, Qiufeng; Jiang, Wunjun; Chen, Zhengrong; Huang, Li; Wang, Meijuan; Ji, Wei; Shao, Xuejun; Yan, Yongdong

    2016-01-01

    To explore the distribution and clinical manifestations of rhinovirus infection in wheezing children, and compare the clinical differences between rhinovirus- and respiratory syncytial virus-induced wheezing. This prospective cohort study was carried out in Children's Hospital of Soochow University from Dec 2012 to Nov 2014. We enrolled consecutive hospitalized children respiratory viruses, by using polymerase chain reaction method for rhinovirus, human bocavirus, and human metapneumovirus, and direct immunofluorescence assay to test for respiratory syncytial virus, adenovirus, parainfluenza virus types 1-3, and influenza virus types A and B. Rhinovirus was a main causative agent isolated in 14.7% of the hospitalized wheezing children in Suzhou, China, being second to respiratory syncytial virus (21.0%). Different from respiratory syncytial virus infection, which peaked in winter months, rhinovirus could be detected all year round, peaked between July and September, and in November. Children with rhinovirus infection were older and presented with more often allergic sensitizations, blood eosinophilia, and leukocytosis than those of respiratory syncytial virus infection. Logistic regression analysis revealed that rhinovirus-infected children experienced earlier wheezing more often than respiratory syncytial virus children (odds ratio, 3.441; 95% confidence interval, 1.187-9.979; p=0.023). Rhinovirus was a main viral pathogen in wheezing children, especially in summer time. Rhinovirus-induced wheezing was different from respiratory syncytial virus, apart from seasonal epidemics; these two groups differed with regard to age, allergic sensitizations, laboratory test, and history of wheezing episodes. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  3. Mortality due to Respiratory Syncytial Virus. Burden and Risk Factors.

    Science.gov (United States)

    Geoghegan, Sarah; Erviti, Anabella; Caballero, Mauricio T; Vallone, Fernando; Zanone, Stella M; Losada, Juan Ves; Bianchi, Alejandra; Acosta, Patricio L; Talarico, Laura B; Ferretti, Adrian; Grimaldi, Luciano Alva; Sancilio, Andrea; Dueñas, Karina; Sastre, Gustavo; Rodriguez, Andrea; Ferrero, Fernando; Barboza, Edgar; Gago, Guadalupe Fernández; Nocito, Celina; Flamenco, Edgardo; Perez, Alberto Rodriguez; Rebec, Beatriz; Ferolla, F Martin; Libster, Romina; Karron, Ruth A; Bergel, Eduardo; Polack, Fernando P

    2017-01-01

    Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear. To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants. This was a prospective, population-based, cross-sectional, multicenter study conducted between 2011 and 2013. Hospitalizations and deaths due to severe lower respiratory tract illness (LRTI) were recorded during the RSV season. All-cause hospital deaths and community deaths were monitored. Risk factors for respiratory failure (RF) and mortality due to RSV were assessed using a hierarchical, logistic regression model. A total of 2,588 (65.5%) infants with severe LRTI were infected with RSV. A total of 157 infants (148 postneonatal) experienced RF or died with RSV. RSV LRTI accounted for 57% fatal LRTI tested for the virus. A diagnosis of sepsis (odds ratio [OR], 17.03; 95% confidence interval [CI], 13.14-21.16 for RF) (OR, 119.39; 95% CI, 50.98-273.34 for death) and pneumothorax (OR, 17.15; 95% CI, 13.07-21.01 for RF) (OR, 65.49; 95% CI, 28.90-139.17 for death) were the main determinants of poor outcomes. RSV was the most frequent cause of mortality in low-income postneonatal infants. RF and death due to RSV LRTI, almost exclusively associated with prematurity and cardiopulmonary diseases in industrialized countries, primarily affect term infants in a developing world environment. Poor outcomes at hospitals are frequent and associated with the cooccurrence of bacterial sepsis and clinically significant pneumothoraxes.

  4. Respiratory syncytial virus hospitalisation trends in children with haemodynamically significant heart disease, 1997-2012.

    Science.gov (United States)

    Chu, Patricia Y; Hornik, Christoph P; Li, Jennifer S; Campbell, Michael J; Hill, Kevin D

    2017-01-01

    The aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the United States of America. Study design The Kids' Inpatient Databases (1997-2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. Weighted multivariable logistic regression and chi-square tests were used to evaluate the trends over time and factors associated with hospitalisation, comparing eras before and after publication of the 2003 American Academy of Pediatrics palivizumab immunoprophylaxis guidelines. Secondary outcomes included in-hospital mortality, morbidity, length of stay, and cost. Overall, 549,265 respiratory syncytial virus-related hospitalisations were evaluated, including 2518 (0.5%) in children with haemodynamically significant heart disease. The incidence of respiratory syncytial virus hospitalisation in children with haemodynamically significant heart disease decreased by 36% when comparing pre- and post-palivizumab guideline eras versus an 8% decline in children without haemodynamically significant heart disease (prespiratory syncytial virus-associated mortality (4.9 versus 0.1%, prespiratory syncytial virus hospitalisation in 2009 was $58,166 (95% CI:$46,017, $70,315). These data provide stakeholders with a means to evaluate the cost-utility of various immunoprophylaxis strategies.

  5. Increased detection of respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses with real-time PCR in samples from patients with respiratory symptoms

    NARCIS (Netherlands)

    van de Pol, Alma C.; van Loon, Anton M.; Wolfs, Tom F. W.; Jansen, Nicolaas J. G.; Nijhuis, Monique; Breteler, Els Klein; Schuurman, Rob; Rossen, John W. A.

    Respiratory samples (n = 267) from hospitalized patients with respiratory symptoms were tested by real-time PCR, viral culture, and direct immunofluorescence for respiratory syncytial virus, influenza virus, parainfluenza viruses, and adenoviruses. Compared with conventional diagnostic tests,

  6. Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, K.; Sakazaki, Hiromi; Murakami, Seiko; Yonezawa, Sumiko [Department of Paediatrics, Izumi Municipal Hospital, Osaka (Japan); Fujimoto, Keiji [Dept. of Radiology, Izumi Municipal Hospital, Osaka (Japan); Seto, Toshiyuki; Tanaka, Katsuji; Hattori, Hideji; Matsuoka, Osamu [Dept. of Paediatrics, Osaka City University Medical School, Osaka (Japan); Murata, Ryosuke [Children`s Medical Centre, Osaka City General Hospital, Osaka (Japan)

    1999-04-01

    We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis. (orig.) With 4 figs., 16 refs.

  7. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Abdoulaye J Dabo

    Full Text Available Increased lung levels of matrix metalloproteinase 9 (MMP9 are frequently observed during respiratory syncytial virus (RSV infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR.

  8. Occurrence of human respiratory syncytial virus in summer in Japan.

    Science.gov (United States)

    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.

  9. Detection of respiratory syncytial virus and rhinovirus in healthy infants.

    Science.gov (United States)

    Hasegawa, Kohei; Linnemann, Rachel W; Avadhanula, Vasanthi; Mansbach, Jonathan M; Piedra, Pedro A; Gern, James E; Camargo, Carlos A

    2015-11-25

    Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic sequencing. Overall, the median age was 3.8 months (IQR 2.0-5.1 months), 56 % were male, and 90% were born >37 weeks. RSV was detected in nasal swabs from infants (1.8%). By contrast, rhinovirus was detected in nasal swabs from 16 infants (14.5%). Molecular typing assay revealed rhinovirus species: six rhinovirus-A (5.5%), one rhinovirus-B (0.9%), eight rhinovirus-C (7.3%), and one untypeable (0.9%). In this cross-sectional study of healthy, community-based infants, RSV was rare (rhinovirus was detected in 14.5% with a predominance of rhinovirus-A and -C. These finding are important for understanding the clinical significance of rhinovirus detection among infants hospitalized for bronchiolitis.

  10. Cytokine responses in primary and secondary respiratory syncytial virus infections.

    Science.gov (United States)

    Ugonna, Kelechi; Douros, Konstantinos; Bingle, Colin D; Everard, Mark L

    2016-06-01

    Primary respiratory syncytial virus (RSV) infections are characterized by high levels of IL-8 and an intense neutrophilia. Little is known about the cytokine responses in secondary infections. Preschool children experiencing RSV secondary infections were recruited from the siblings of infants admitted to hospital with RSV acute bronchiolitis. Fifty-one infants with acute bronchiolitis (39 RSV positive, 12 RSV negative) and 20 age-matched control infants were recruited. In addition, seven older siblings of infants from the RSV-positive cohort and confirmed RSV infection were recruited. Samples of nasal secretions were obtained using a flocked swab, and secretions extracted using centrifugation. Cytokine bead array was used to obtain levels of interleukin (IL)-17A, IL-8, IL-6, IL-21, and tumor necrosis factor-α. Levels of IL-8 and IL-6 were significantly lower in the RSV-positive siblings compared with the RSV-positive infants. There were no significant differences between levels of the other cytokines in the primary and secondary infections. The very high levels of IL-8 and IL-6 response characteristic of the primary RSV infection was not observed in secondary RSV-positive infections and this did not appear to be due to a global reduction in cytokine production.

  11. Challenges and Opportunities in Developing Respiratory Syncytial Virus Therapeutics

    Science.gov (United States)

    Simões, Eric A. F.; DeVincenzo, John P.; Boeckh, Michael; Bont, Louis; Crowe, James E.; Griffiths, Paul; Hayden, Frederick G.; Hodinka, Richard L.; Smyth, Rosalind L.; Spencer, Keith; Thirstrup, Steffen; Walsh, Edward E.; Whitley, Richard J.

    2015-01-01

    Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial virus (RSV) infections. The practicalities of clinical trials and establishing reliable outcome measures in different target groups were discussed in the context of the regulatory pathways that could accelerate the translation of promising compounds into licensed agents. RSV drug development is hampered by the perceptions of a relatively small and fragmented market that may discourage major pharmaceutical company investment. Conversely, the public health need is far too large for RSV to be designated an orphan or neglected disease. Recent advances in understanding RSV epidemiology, improved point-of-care diagnostics, and identification of candidate antiviral drugs argue that the major obstacles to drug development can and will be overcome. Further progress will depend on studies of disease pathogenesis and knowledge provided from controlled clinical trials of these new therapeutic agents. The use of combinations of inhibitors that have different mechanisms of action may be necessary to increase antiviral potency and reduce the risk of resistance emergence. PMID:25713060

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

    Science.gov (United States)

    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

  13. Simultaneous influenza and respiratory syncytial virus infection in human respiratory tract

    Science.gov (United States)

    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.

  14. Codetection of respiratory syncytial virus in habituated wild western lowland gorillas and humans during a respiratory disease outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:68081766 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.252, year: 2016

  15. Codetection of Respiratory Syncytial Virus in Habituated Wild Western Lowland Gorillas and Humans During a Respiratory Disease Outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:60077344 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: EE - Microbiology, Virology Impact factor: 2.252, year: 2016

  16. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity

    NARCIS (Netherlands)

    Bont, L; Heijnen, CJ; Kavelaars, A; van Aalderen, WMC; Brus, F; Draaisma, JMT; Pekelharing-Berghuis, M; van Diemen-Steenvoorde, RAAM; Kimpen, JLL

    2001-01-01

    To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to

  17. Respiratory syncytial viral infections in young children : risk assessment and prevention

    NARCIS (Netherlands)

    E. Rietveld (Edwin)

    2003-01-01

    textabstractRespiratory syncytial virus is the main cause of lower respiratory tract infections in infants and young children. Although almost all children are infected before the age of two years, less than 2% develop severe disease necessitating hospitalisation. Risk factors for severe RSV

  18. Cost-effectiveness of potential infant vaccination against respiratory syncytial virus infection in The Netherlands

    NARCIS (Netherlands)

    Meijboom, M. J.; Rozenbaum, M. H.; Benedictus, A.; Luytjes, W.; Kneyber, M. C. J.; Wilschut, J. C.; Hak, E.; Postma, M. J.

    2012-01-01

    Introduction: Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory illness in infants, infecting virtually every child before the age of 2 years. Currently, several Phase 1 trials with RSV vaccines in infants are ongoing or have been completed. As yet, no efficacy

  19. Neutrophils in respiratory syncytial virus infection : A target for asthma prevention

    NARCIS (Netherlands)

    Geerdink, Ruben J.; Pillay, Janesh; Meyaard, Linde; Bont, LJ

    2015-01-01

    Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast

  20. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J. B. M.; Bos, A. P.; Lutter, R.; Rossen, J. W. A.; Schuurman, R.

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  1. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis.

    NARCIS (Netherlands)

    Belderbos, M.E.; Houben, M.L.; Wilbrink, B.; Lentjes, E.G.W.M.; Bloemen, E.M.; Kimpen, J.L.L.; Rovers, M.M.; Bont, L.

    2011-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. OBJECTIVE: To determine the association between plasma vitamin D

  2. Aspects of Innate and Adaptive Immune responses during Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Lukens, M.V.

    2009-01-01

    Respiratory Syncytial Virus (RSV) infections are a major cause of lower respiratory tract disease and represent a major disease burden in infants, immune compromised patients and the elderly. Despite the identification and isolation of the virus in 1956, extensive efforts since then to develop a

  3. Enhanced adherence of Strontococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus

    NARCIS (Netherlands)

    Hament, JM; Aerts, PC; Fleer, A; Van Dijk, H; Kimpen, JLL; Wolfs, TFW

    In the present study, we analyzed the effect of a preceding respiratory syncytial virus (RSV) infection of human respiratory epithelial cells on the adherence of Streptococcus pneumoniae tested by means of a cytometric fluorescence assay. Adherence of clinically relevant pneumococcal serotypes 3, 9,

  4. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  5. Respiratory disease associated with bovine coronavirus infection in cattle herds in Southern Italy.

    Science.gov (United States)

    Decaro, Nicola; Campolo, Marco; Desario, Costantina; Cirone, Francesco; D'Abramo, Maria; Lorusso, Eleonora; Greco, Grazia; Mari, Viviana; Colaianni, Maria Loredana; Elia, Gabriella; Martella, Vito; Buonavoglia, Canio

    2008-01-01

    Four outbreaks of bovine respiratory disease (BRD) associated with bovine coronavirus (BCoV) infection in Italian cattle herds were reported. In 3 outbreaks, BRD was observed only in 2-3-month-old feedlot calves, whereas in the remaining outbreak, lactating cows, heifers, and calves were simultaneously affected. By using reverse transcription polymerase chain reaction (RT-PCR), BCoV RNA was detected in all outbreaks without evidence of concurrent viral pathogens (i.e., bovine respiratory syncytial virus, bovine herpesvirus type 1, bovine viral diarrhea virus, bovine parainfluenza virus). Common bacteria of cattle were recovered only from 2 outbreaks of BRD: Staphylococcus spp. and Proteus mirabilis (outbreak 1) and Mannheimia haemolytica (outbreak 4). A recently established real-time RT-PCR assay showed that viral RNA loads in nasal secretions ranged between 3.10 x 10(2) and 7.50 x 10(7) RNA copies/microl of template. Bovine coronavirus was isolated from respiratory specimens from all outbreaks except outbreak 1, in which real-time RT-PCR found very low viral titers in nasal swabs.

  6. Human Respiratory Syncytial Virus load normalized by cell quantification as predictor of acute respiratory tract infection.

    Science.gov (United States)

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

    2018-01-05

    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 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection.

    Science.gov (United States)

    Kirchhoff, Jana; Uhlenbruck, Sabine; Goris, Katherina; Keil, Günther M; Herrler, Georg

    2014-02-18

    Bovine respiratory disease complex (BRDC) is the major cause of serious respiratory tract infections in calves. The disease is multifactorial, with either stress or reduced immunity allowing several pathogens to emerge. We investigated the susceptibility of bovine airway epithelial cells (BAEC) to infection by the three major viruses associated with the BRDC: bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza virus type 3 (BPIV3). For this purpose, two culture systems for well-differentiated BAEC were used: the air-liquid interface (ALI) system, where filter-grown BAEC differentiate into a pseudostratified respiratory epithelium and precision-cut lung slices (PCLS) where BAEC are maintained in the original tissue organisation. Comparative infection studies demonstrated that entry and release of BPIV3 occurred specifically via the apical membrane with ciliated cells being the major target cells. By contrast, airway epithelial cells were largely resistant to infection by BHV-1. When the epithelial barrier was abolished by opening tight junctions or by injuring the cell monolayer, BHV-1 infected mainly basal cells. Respiratory epithelial cells were also refractory to infection by BRSV. However, this virus infected neither differentiated epithelial cells nor basal cells when the integrity of the epithelial barrier was destroyed. In contrast to cells of the airway epithelium, subepithelial cells were susceptible to infection by BRSV. Altogether, these results indicate that the three viruses of the same disease complex follow different strategies to interact with the airway epithelium. Possible entry mechanisms are discussed.

  8. PROPHYLACTIC ADMINISTRATION OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN TO HIGH-RISK INFANTS AND YOUNG-CHILDREN

    NARCIS (Netherlands)

    GROOTHUIS, [No Value; SIMOES, EAF; LEVIN, MJ; HALL, CB; LONG, CE; RODRIGUEZ, WJ; ARROBIO, J; MEISSNER, HC; FULTON, DR; WELLIVER, RC; TRISTRAM, DA; SIBER, GR; PRINCE, GA; VANRADEN, M; HEMMING, VG

    1993-01-01

    Background. Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common

  9. RESPIRATORY SYNCYTIAL VIRUS INFECTION AMONG YOUNG CHILDREN WITH ACUTE RESPIRATORY INFECTION

    Directory of Open Access Journals (Sweden)

    M. Milani

    2003-08-01

    Full Text Available Respiratory syncytial virus (RSV is the major cause of lower respiratory tract infections in infants,and also an important factor for hospitalization during the winter months. To determine the prevalence and importance of RSV as a cause of acute lower respiratory tract infection, we carried out a prospective study during 5 months period from November to March 1998 in 6 pediatric hospitals. A nasopharyngeal aspirate was obtained for detection of RSV in all cases. Sociodemographic data, clinical signs, diagnosis and hospital admissions were documented. During this study period, 365 young infants (51.5% male, 48.5% female with respiratory tract infection were visited in 6 hospitals. The median age of patients was 24 months (range: 1 month to 5 years.RSV infection was found in 70 out of 365 patients (19.18%.Among the 70 children with RSV infection, 29 patients (41.42% were under 12 months of age.The main clinical manifestations of RSV infection were cough (88.57% and coryza (78.57%. There were no significant differences between patients who were tested positive for RSV and those who were tested negative with regard to demographic variables and clinical diagnoses. This study indicates that RSV is an important cause of respiratory tract infection in infants and young children .Distinguishing RSV from other respiratory infection is difficult because of the similarity in clinical presentation among children.

  10. Determinants of asthma after severe respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Bacharier, Leonard B; Cohen, Rebecca; Schweiger, Toni; Yin-Declue, Huiquing; Christie, Chandrika; Zheng, Jie; Schechtman, Kenneth B; Strunk, Robert C; Castro, Mario

    2012-07-01

    The development of asthma after respiratory syncytial virus (RSV) bronchiolitis has been demonstrated in case-control studies, although the determinants of post-RSV asthma remain undefined. We sought to evaluate the potential determinants of physician-diagnosed asthma after severe RSV bronchiolitis during infancy. We enrolled 206 children during an initial episode of severe RSV bronchiolitis at 12 months of age or less in a prospective cohort study and followed these children for up to 6 years. In a subset of 81 children, we analyzed CCL5 (RANTES) mRNA expression in upper airway epithelial cells. Forty-eight percent of children had physician-diagnosed asthma before the seventh birthday. Independent determinants significantly associated with increased risk for physician-diagnosed asthma by the seventh birthday included maternal asthma (odds ratio [OR], 5.2; 95% CI, 1.7-15.9; P = .004), exposure to high levels of dog allergen (OR, 3.2; 95% CI, 1.3-7.7; P = .012), aeroallergen sensitivity at age 3 years (OR, 10.7; 95% CI, 2.1-55.0; P = .005), recurrent wheezing during the first 3 years of life (OR, 7.3; 95% CI, 1.2-43.3; P = .028), and CCL5 expression in nasal epithelia during acute RSV infection (OR, 3.8; 95% CI, 1.2-2.4; P bronchiolitis have a subsequent asthma diagnosis. The presence of increased CCL5 levels in nasal epithelia at the time of bronchiolitis or the development of allergic sensitization by age 3 years are associated with increased likelihood of subsequent asthma. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  11. Treatment of respiratory syncytial virus bronchiolitis : 1995 poll of members of the European Society for Paediatric Infectious Diseases

    NARCIS (Netherlands)

    Kimpen, JLL; Schaad, UB

    Background. Among the lower respiratory tract infections during infancy requiring hospitalization, respiratory syncytial virus (RSV) bronchiolitis is the most frequent disease entity. Nevertheless treatment remains controversial. Methods. A poll among the European Society for Paediatric Infectious

  12. Antiviral activity of carnosic acid against respiratory syncytial virus

    Science.gov (United States)

    2013-01-01

    Background Human respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study. Methods Effects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs. Results Among the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV. Conclusions The current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic

  13. The Use of Humanized Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    Marcello Lanari

    2013-01-01

    Full Text Available Monoclonal antibodies are widely used both in infants and in adults for several indications. Humanized monoclonal antibodies (palivizumab have been used for many years for the prevention of respiratory syncytial virus infection in pediatric populations (preterm infants, infants with chronic lung disease or congenital heart disease at high risk of severe and potentially lethal course of the infection. This drug was reported to be safe, well tolerated and effective to decrease the hospitalization rate and mortality in these groups of infants by several clinical trials. In the present paper we report the development and the current use of monoclonal antibodies for prophylaxis against respiratory syncytial virus.

  14. Pasteurella multocida and bovine respiratory disease.

    Science.gov (United States)

    Dabo, S M; Taylor, J D; Confer, A W

    2007-12-01

    Pasteurella multocida is a pathogenic Gram-negative bacterium that has been classified into three subspecies, five capsular serogroups and 16 serotypes. P. multocida serogroup A isolates are bovine nasopharyngeal commensals, bovine pathogens and common isolates from bovine respiratory disease (BRD), both enzootic calf pneumonia of young dairy calves and shipping fever of weaned, stressed beef cattle. P. multocida A:3 is the most common serotype isolated from BRD, and these isolates have limited heterogeneity based on outer membrane protein (OMP) profiles and ribotyping. Development of P. multocida-induced pneumonia is associated with environmental and stress factors such as shipping, co-mingling, and overcrowding as well as concurrent or predisposing viral or bacterial infections. Lung lesions consist of an acute to subacute bronchopneumonia that may or may not have an associated pleuritis. Numerous virulence or potential virulence factors have been described for bovine respiratory isolates including adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide, polysaccharide capsule and a variety of OMPs. Immunity of cattle against respiratory pasteurellosis is poorly understood; however, high serum antibodies to OMPs appear to be important for enhancing resistance to the bacterium. Currently available P. multocida vaccines for use in cattle are predominately traditional bacterins and a live streptomycin-dependent mutant. The field efficacy of these vaccines is not well documented in the literature.

  15. Respiratory syncytial virus prophylaxis in children with cardiac disease: a retrospective single-centre study.

    Science.gov (United States)

    Butt, Michelle; Symington, Amanda; Janes, Marianne; Steele, Susan; Elliott, Louann; Chant-Gambacort, Catherine; Mondal, Tapas; Paes, Bosco

    2014-04-01

    To examine the characteristics of congenital heart disease patients hospitalised with respiratory syncytial virus infection after prophylaxis and determine the associated comorbidities and the incidence of breakthrough respiratory syncytial virus infections. This is a retrospective, single-centre study that was conducted over a period of 7 years. Respiratory syncytial virus infection was identified by classification codes and confirmed by virological tests. Data on baseline demographics, cardiac anomalies, other underlying disease, criteria for hospitalisation, type of respiratory illness and management, complications, and palivizumab prophylaxis were analysed by standard descriptive methods and comparative statistics. A total of 30 patients were enrolled. The majority were ≤ 2 years (n = 24). The mean admission age was 15.1 months (standard deviation = 18.3). In all, 90% were acyanotic, 40% had haemodynamically significant disease, and 60% had ≥ 1 underlying medical illness. Patients were admitted with: respiratory distress (86.7%), hypoxaemia (66.7%), fever (60%), inability to maintain oral intake (36.7%), and apnoea (16.7%). More than 50% required mechanical ventilation and intensive care with a median stay of 11 days (range: 1-43); the length of hospital stay for all children was 10 days (range: 1-65). Complications included: concurrent bacterial sepsis (20%), electrolyte abnormalities (16.7%), and worsening pulmonary hypertension (13.3%). Of 10 infants ≤ 2 years with haemodynamically significant heart disease, four had received prophylaxis. There was one death, which was attributed to respiratory syncytial virus infection. Overall, 185 infants ≤ 2 years with haemodynamically significant cardiac disease received prophylaxis. In all, six qualifying infants missed immunisation and were hospitalised. Breakthrough respiratory syncytial virus infections occurred in 2.2%, demonstrating good efficacy of palivizumab in this population compared with the original

  16. Respiratory syncytial virus infection of the lower respiratory tract: radiological findings in 108 children

    Energy Technology Data Exchange (ETDEWEB)

    Kern, S.; Uhl, M. [Dept. of Diagnostic Radiology, University Hospital Freiburg (Germany); Berner, R.; Schwoerer, T. [Dept. of Pediatrics, University Hospital Freiburg (Germany); Langer, M. [Dept. of Diagnostic Radiology, University Hospital Freiburg (Germany)

    2001-12-01

    For years the typical appearance of respiratory syncytial virus (RSV)-induced infection of the lower respiratory tract has been discussed. All available studies have led to different results. The aim of this study was to control these results, with 108 children. The age range was 1 day to 10 years (median 7 months). Within 72 h of admission, all children developed an RSV infection of the lower respiratory tract. Chest X-rays (pa-view) of 55 children under, and 53 children over, the age of 6 months (10/53>24 months) were evaluated. The diagnosis of RSV and the chest X-ray were mostly done on the same day. The major radiological findings of the two age-groups were compared by Wilcoxon's unpaired rank sum test. Major radiological findings were: normal chest X-ray (30%), central pneumonia (32%) or peribronchitis (26%). There was no statistical significance between the age-groups. Other findings were emphysema (11%), pleural effusion (6%), lobar- or broncho-pneumonia (each 6%), atelectasis (5%) or pneumothorax in one case. Therefore, the most common radiological findings in RSV-induced infection of the lower respiratory tract, supported by our results (RSV infection without bacterial superinfection) are central pneumonia, peribronchitis or normal chest X-ray. Thus an age-group separation into under or over 6 months is no longer necessary. (orig.)

  17. Interference between respiratory syncytial virus and rhinovirus in respiratory tract infections in children.

    Science.gov (United States)

    Karppinen, S; Toivonen, L; Schuez-Havupalo, L; Waris, M; Peltola, V

    2016-02-01

    An acute viral respiratory tract infection might prevent infections by other viruses because of the antiviral innate immune response. However, with the use of PCR methods, simultaneous detection of two or more respiratory viruses is frequent. We analysed the effect of respiratory syncytial virus (RSV) infection on the occurrence of simultaneous rhinovirus (RV) infection in children within a birth cohort study setting. We used PCR for virus detection in nasal swabs collected from children with an acute respiratory tract infection at the age of 0-24 months and from healthy control children, who were matched for age and date of sample collection. Of 226 children with RSV infections, 18 (8.0%) had co-infections with RV, whereas RV was detected in 31 (14%) of 226 control children (p 0.049 by chi-square test). Adjustment for sex, number of siblings and socio-economic status strengthened the negative association between RSV and RV (OR 0.46, 95% CI 0.24-0.90; p 0.02). The median durations of symptoms (cough, rhinorrhoea, or fever) were 11 days in children with single RSV infections and 14 days in children with RSV-RV co-infections (p 0.02). Our results suggest that the presence of RSV reduces the probability of RV infection, but that, if a co-infection occurs, both viruses cause clinical symptoms. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Vaccine Safety and Efficacy Evaluation of a Recombinant Bovine Respiratory Syncytial Virus (BRSV) with Deletion of the SH Gene and Subunit Vaccines Based On Recombinant Human RSV Proteins: N-nanorings, P and M2-1, in Calves with Maternal Antibodies

    Science.gov (United States)

    Blodörn, Krister; Hägglund, Sara; Fix, Jenna; Dubuquoy, Catherine; Makabi-Panzu, Boby; Thom, Michelle; Karlsson, Per; Roque, Jean-Louis; Karlstam, Erika; Pringle, John; Eléouët, Jean-François; Riffault, Sabine; Taylor, Geraldine; Valarcher, Jean François

    2014-01-01

    The development of safe and effective vaccines against both bovine and human respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV-specific maternally-derived antibodies (MDA) remains a high priority in human and veterinary medicine. Herein, we present safety and efficacy results from a virulent BRSV challenge of calves with MDA, which were immunized with one of three vaccine candidates that allow serological differentiation of infected from vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (ΔSHrBRSV), and two subunit (SU) formulations based on HRSV-P, -M2-1, and -N recombinant proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion (Montanide ISA71VG, SUMont) or immunostimulating complex matrices (AbISCO-300, SUAbis). Whereas all control animals developed severe respiratory disease and shed high levels of virus following BRSV challenge, ΔSHrBRSV-immunized calves demonstrated almost complete clinical and virological protection five weeks after a single intranasal vaccination. Although mucosal vaccination with ΔSHrBRSV failed to induce a detectable immunological response, there was a rapid and strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and local T cell response following challenge with virulent BRSV. Calves immunized twice intramuscularly, three weeks apart with SUMont were also well protected two weeks after boost. The protection was not as pronounced as that in ΔSHrBRSV-immunized animals, but superior to those immunized twice subcutaneously three weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were non-neutralizing and not directed against BRSV F or G proteins. When formulated as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong systemic cross-protective cell-mediated immune responses detectable already after priming. ΔSHrBRSV and SUMont are two promising DIVA-compatible vaccines, apparently inducing protection by

  19. Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease.

    Science.gov (United States)

    Cortjens, Bart; de Boer, Onno J; de Jong, Rineke; Antonis, Adriaan Fg; Sabogal Piñeros, Yanaika S; Lutter, René; van Woensel, Job Bm; Bem, Reinout A

    2016-02-01

    Human respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation in the lungs and occlusion of small airways by DNA-rich mucus plugs are characteristic features of severe RSV-LRTD. Activated neutrophils can release neutrophil extracellular traps (NETs), extracellular networks of DNA covered with antimicrobial proteins, as part of the first-line defence against pathogens. NETs can trap and eliminate microbes; however, abundant NET formation may also contribute to airway occlusion. In this study, we investigated whether NETs are induced by RSV and explored their potential anti-viral effect in vitro. Second, we studied NET formation in vivo during severe RSV-LRTD in infants and bovine RSV-LRTD in calves, by examining bronchoalveolar lavage fluid and lung tissue sections, respectively. NETs were visualized in lung cytology and tissue samples by DNA and immunostaining, using antibodies against citrullinated histone H3, elastase and myeloperoxidase. RSV was able to induce NET formation by human neutrophils in vitro. Furthermore, NETs were able to capture RSV, thereby precluding binding of viral particles to target cells and preventing infection. Evidence for the formation of NETs in the airways and lungs was confirmed in children with severe RSV-LRTD. Detailed histopathological examination of calves with RSV-LRTD showed extensive NET formation in dense plugs occluding the airways, either with or without captured viral antigen. Together, these results suggest that, although NETs trap viral particles, their exaggerated formation during severe RSV-LRTD contributes to airway obstruction. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Animal models for studying respiratory syncytial virus infection and its long term effects on lung function.

    Science.gov (United States)

    Domachowske, Joseph B; Bonville, Cynthia A; Rosenberg, Helene F

    2004-11-01

    Human respiratory syncytial virus (hRSV) infection causes a spectrum of illnesses ranging from mild infection to life-threatening bronchiolitis and respiratory failure. Human studies on the pathogenesis of RSV infection are invaluable, but animal models permit advances with the use of experimental strategies that would be inappropriate in human studies. We review the advantages and disadvantages of various animal models for the study of hRSV infection. No animal model of hRSV infection replicates the complete spectrum of disease severity seen in humans. Available models differ in their ability to incorporate genetic technology and to allow the study of immunity, vaccine efficacy and treatment interventions. Although hRSV establishes disease in primates, this advantage is outweighed by the impracticalities and cost of using such models. The study of bovine RSV infection in calves is appealing because of parallels with human disease. Among rodent models, BALB/c mice have helped delineate the mechanisms underlying vaccine-enhanced RSV disease, and cotton rats have been used for preclinical testing. The single major disadvantage of studying hRSV in rodent models is the limited extent to which this host-restricted human pneumovirus replicates in mouse lung tissue. The rodent-specific Pneumovirus pathogen, pneumonia virus of mice, causes an infection that mirrors severe bronchiolitis and pneumonia in infants infected with RSV, including robust virus replication with profound inflammation. The recent development of the pneumonia virus of mice model has permitted exploration of the mechanisms of severe Pneumovirus disease in vivo with the use of sophisticated genetic tools and genetically manipulated mouse strains.

  1. Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze

    NARCIS (Netherlands)

    Schuurhof, Annemieke; Janssen, Riny; de Groot, Hanneke; Hodemaekers, Hennie M.; de Klerk, Arja; Kimpen, Jan L. L.; Bont, Louis

    2011-01-01

    Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW). Animal studies have suggested that interleukin (IL)-10 plays a critical role in the pathogenesis of RSV

  2. Molecular evolution of respiratory syncytial virus fusion gene, Canada, 2006-2010.

    Science.gov (United States)

    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; Boivin, Guy

    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.

  3. Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015

    DEFF Research Database (Denmark)

    Jepsen, Martin T; Trebbien, Ramona; Emborg, Hanne Dorthe

    2018-01-01

    For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual...... be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants....

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

    Science.gov (United States)

    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.

  5. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    Risk factors for admission and the role of respiratory syncytial virus-specific cytotoxic T-lymphocyte responses in children with acute bronchiolitis. ... CTL responses in peripheral blood of immunocompetent RSV-infected children suggest an alternative method of induction of immunity or compartmentalisation of immune cells.

  6. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    (CTL) activity, enable respiratory syncytial virus (RSV)- specific CTL activity to be studied in infants with bronchiolitis for the first time. We evaluated risk factors for admission of children with acute bronchiolitis and determined the role of CTL responses in those infected with. RSV. Method. Children between 3 and 24 months ...

  7. Cost-effectiveness of respiratory syncytial virus (RSV) vaccination of dutch elderly

    NARCIS (Netherlands)

    Pouwels, K.; Meijboom, M.; Luytjes, W.; Hak, E.; Postma, M.

    2011-01-01

    OBJECTIVES: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of morbidity, mortality and health-care resource use in the elderly. Therefore we determined whether there are specific levels of vaccine cost and effectiveness for which a hypothetical RSV-vaccine for

  8. Respiratory syncytial virus-specific CD8(+) memory T cell responses in elderly persons

    NARCIS (Netherlands)

    de Bree, GJ; Heidema, J; van Leeuwen, EMM; van Bleek, GM; Jonkers, RE; Jansen, HM; van Lier, RAW; Out, TA

    2005-01-01

    Background. We investigated respiratory syncytial virus (RSV)-specific CD8(+) memory T cell responses in healthy control participants (n = 31) and in patients with chronic obstructive pulmonary disease (COPD) n = 9), with respect to frequency, memory phenotype, and proliferative requirements.

  9. Radiological findings in children with respiratory syncytial virus infection: Relationship to clinical and bacteriological findings

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, J.; Nordshus, T.; Westvik, J.; Carlsen, K.H.; Oerstadvik, I.; Eng, J.

    1986-02-01

    Respiratory syncytial virus (RSV) is a frequent cause of bronchiolitis leading to acute admission to hospital in the winter months. A wide range of findings accompanies this disease and the appearances are seldom completely diagnostic. Associated bacterial co-infections are common and we have shown an association with atelectasis among patients with pathogenic bacteria in the nasopharynx. (orig.).

  10. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization

    DEFF Research Database (Denmark)

    Kristensen, Kim; Hjuler, Thomas; Ravn, Henrik

    2012-01-01

    Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register...

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

    Science.gov (United States)

    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.

  12. Concurrent detection of other respiratory viruses in children shedding viable human respiratory syncytial virus.

    Science.gov (United States)

    Gagliardi, T B; Paula, F E; Iwamoto, M A; Proença-Modena, J L; Santos, A E; Camara, A A; Cervi, M C; Cintra, O A L; Arruda, E

    2013-10-01

    Human respiratory syncytial virus (HRSV) is an important cause of respiratory disease. The majority of studies addressing the importance of virus co-infections to the HRSV-disease have been based on the detection of HRSV by RT-PCR, which may not distinguish current replication from prolonged shedding of remnant RNA from previous HRSV infections. To assess whether co-detections of other common respiratory viruses are associated with increased severity of HRSV illnesses from patients who were shedding viable-HRSV, nasopharyngeal aspirates from children younger than 5 years who sought medical care for respiratory infections in Ribeirão Preto (Brazil) were tested for HRSV by immunofluorescence, RT-PCR and virus isolation in cell culture. All samples with viable-HRSV were tested further by PCR for other respiratory viruses. HRSV-disease severity was assessed by a clinical score scale. A total of 266 samples from 247 children were collected and 111 (42%) were HRSV-positive. HRSV was isolated from 70 (63%), and 52 (74%) of them were positive for at least one additional virus. HRSV-positive diseases were more severe than HRSV-negative ones, but there was no difference in disease severity between patients with viable-HRSV and those HRSV-positives by RT-PCR. Co-detection of other viruses did not correlate with increased disease severity. HRSV isolation in cell culture does not seem to be superior to RT-PCR to distinguish infections associated with HRSV replication in studies of clinical impact of HRSV. A high rate of co-detection of other respiratory viruses was found in samples with viable-HRSV, but this was not associated with more severe HRSV infection. Copyright © 2013 Wiley Periodicals, Inc.

  13. Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease.

    Science.gov (United States)

    Kim, Yae-Jean; Guthrie, Katherine A; Waghmare, Alpana; Walsh, Edward E; Falsey, Ann R; Kuypers, Jane; Cent, Anne; Englund, Janet A; Boeckh, Michael

    2014-04-15

    Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm(3) at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm(3) at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

  14. RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function

    OpenAIRE

    Tian, Jane; Huang, Kelly; Krishnan, Subramaniam; Svabek, Catherine; Rowe, Daniel C.; Brewah, Yambasu; Sanjuan, Miguel; Patera, Andriani C.; Kolbeck, Roland; Herbst, Ronald; Sims, Gary P.

    2013-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognitio...

  15. The promise and progress of RNA-interference-based antiviral therapy for respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    V. V. Vysochinskayа

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is a major cause of morbidity in infants, young children, and the elderly worldwide. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. Recent progress in studies of the mechanism of RNA interference suggests the formation of a new class of antiviral drugs in the treatment of RSV infection and related respiratory diseases.

  16. TLR-4 and CD14 Polymorphisms in Respiratory Syncytial Virus Associated Disease

    Directory of Open Access Journals (Sweden)

    Beena Puthothu

    2006-01-01

    Full Text Available Respiratory syncytial virus (RSV is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14.

  17. Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

    Directory of Open Access Journals (Sweden)

    Kimpen Jan LL

    2002-06-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.

  18. Infection of differentiated airway epithelial cells from caprine lungs by viruses of the bovine respiratory disease complex.

    Science.gov (United States)

    Kirchhoff, Jana; Uhlenbruck, Sabine; Keil, Günther M; Schwegmann-Wessels, Christel; Ganter, Martin; Herrler, Georg

    2014-05-14

    Bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (BPIV3) and bovine herpesvirus type 1 (BHV-1) are important pathogens associated with the bovine respiratory disease complex (BRDC). Non-bovine ruminants such as goats may also be infected and serve as a virus reservoir to be considered in the development of control strategies. To evaluate the susceptibility of caprine airway epithelial cells to infection by viruses of BRDC, we established a culture system for differentiated caprine epithelial cells. For this purpose, we generated precision-cut lung slices (PCLS), in which cells are retained in their original structural configuration and remain viable for more than a week. The three bovine viruses were found to preferentially infect different cell types. Ciliated epithelial cells were the major target cells of BPIV3, whereas BHV-1 preferred basal cells. Cells infected by BRSV were detected in submucosal cell layers. This spectrum of susceptible cells is the same as that reported recently for infected bovine PCLS. While infection of caprine cells by BRSV and BPIV3 was as efficient as that reported for bovine cells, infection of caprine cells by BHV-1 required a tenfold higher dose of infectious virus as compared to infection of bovine airway cells. These results support the notion that non-bovine ruminants may serve as a reservoir for viruses of BRDC and introduce a culture system to analyze virus infection of differentiated airway epithelial cells from the caprine lung. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Prevalence of respiratory syncytial virus infection among hospitalized children presenting with acute lower respiratory tract infections.

    Science.gov (United States)

    Gupta, Soham; Shamsundar, Ranjani; Shet, Anita; Chawan, Rashmi; Srinivasa, Hiresave

    2011-12-01

    To evaluate the prevalence of RSV among hospitalized young children presenting with ALRI in Bangalore, India. Respiratory syncytial virus (RSV) antigen detection was performed by direct fluorescent antibody (DFA) staining on 77 nasopharyngeal wash samples collected from hospitalized children below 2 years of age with a diagnosis of acute lower respiratory tract infection (ALRI). Out of 77 samples tested for RSV with DFA, 17 (22.1%) were found RSV-positive with a mean age of 8.24 ± 7.21 months (M:F = 1.8:1). Three children had congenital cardiac disease and one child had a history of prematurity. One child had re-infection within one month of primary infection. RSV-infected children were more likely to have a diagnosis of bronchiolitis than RSV-negative children (p infection is a significant cause of morbidity among children presenting with ALRI in southern India. In resource-limited settings, DFA can be used as an important tool for rapid detection of RSV and can potentially eliminate prolonged hospitalization and unnecessary use of antibiotics.

  20. Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    C Lin

    Full Text Available Our previous studies showed that bovine respiratory syncytial virus (BRSV followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2 epithelial cells with H. somni concentrated culture supernatant (CCS stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2 and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

  1. High Concentrations of Amniotic Fluid Proinflammatory Cytokines in Healthy Neonates Are Associated With Low Risk of Respiratory Syncytial Virus Bronchiolitis

    NARCIS (Netherlands)

    Houben, Michiel L.; Rovers, Maroeska M.; Wilbrink, Berry; Belderbos, Mirjam E.; Bloemen-Carlier, Eltje M.; Visser, Gerard H. A.; Kimpen, Jan L. L.; Bont, Louis

    Background: The burden of respiratory syncytial virus (RSV) bronchiolitis in individual children and their families, the medical system and society is considerable. Mechanisms underlying RSV bronchiolitis in healthy term infants are largely unknown. Sterile intraamniotic inflammation and

  2. High concentrations of amniotic fluid proinflammatory cytokines in healthy neonates are associated with low risk of respiratory syncytial virus bronchiolitis.

    NARCIS (Netherlands)

    Houben, M.L.; Rovers, M.M.; Wilbrink, B.; Belderbos, M.E.; Bloemen-Carlier, E.M.; Visser, G.H.; Kimpen, J.L.L.; Bont, L.

    2012-01-01

    BACKGROUND: : The burden of respiratory syncytial virus (RSV) bronchiolitis in individual children and their families, the medical system and society is considerable. Mechanisms underlying RSV bronchiolitis in healthy term infants are largely unknown. Sterile intraamniotic inflammation and

  3. Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis

    NARCIS (Netherlands)

    van Woensel, JBM; Wolfs, TFW; vanAalderen, WMC; Brand, PLP; Kimpen, JLL

    Background - Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. Methods - A randomised double blind trial was conducted in children up to

  4. Pathogens of bovine respiratory disease in North American feedlots conferring multidrug resistance via integrative conjugative elements.

    Science.gov (United States)

    Klima, Cassidy L; Zaheer, Rahat; Cook, Shaun R; Booker, Calvin W; Hendrick, Steve; Alexander, Trevor W; McAllister, Tim A

    2014-02-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD.

  5. Seroprevalence of some bovine viral respiratory diseases among non vaccinated cattle in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Mohamed Abd El Fatah Mahmoud

    2013-02-01

    Full Text Available Aim: Four viral pathogens, bovine viral diarrhea virus (BVDV, and bovine herpes virus type 1 (BHV-1, bovine parainfluenza type 3 virus (PI-3V, bovine respiratory syncytial virus (BRSV are mainly associated with bovine respiratory diseases that cause major economic losses in the dairy cattle industry. This study aimed to document exposure of cattle in Saudi Arabia to infectious BVDV, BHV-1, PI-3V and BRSV viruses in non vaccinated cattle in order to obtain epidemiological and immunological information. Materials and Methods: In the present study, 460 random serum samples obtained from non vaccinated cattle in five districts (Riyadh, Eastern Province, Jizan, Najran, Asir of Saudi Arabia between January to March 2011. These samples were tested for presence of antibodies against BVDV, BHV-1, BRSV and PIV-3 by commercial indirect ELISA kits. Results: Our findings displayed that Seropositivity rates were 26 % for BVD, 17.4 % for BHV-1, 69.1 % for PI-3V and 75.6 % for BRSV in the sampled population. In addition, coinfections with more than one virus were considerably common among non-vaccinated dairy cattle. Conclusion: These results indicate that exposure to these agents is common within the study areas. Preventive and control measures against these infectious agents should therefore be adopted. [Vet World 2013; 6(1.000: 1-4

  6. Human respiratory syncytial virus and metapneumovirus in patients with acute respiratory infection in Colombia, 2000 - 2011.

    Science.gov (United States)

    Barbosa Ramirez, Juliana; Pulido Dominguez, Paola; Rey Benito, Gloria; Mendez Rico, Jairo; Castellanos, Jaime; Páez Martinez, Andrés

    2014-08-01

    To describe the epidemiology of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) in Colombia from 2000 - 2011, including seasonal trends. Nasopharyngeal aspirates and/or throat swabs from 14 870 patients with acute respiratory infections (ARI) were studied. Two subgroups were analyzed using molecular biology techniques. The first consisted of 264 RSV indirect fluorescence assay (IFA)-positive samples, the second of 264 RSV IFA-negative samples. RSV and hMPV were detected using reverse transcription polymerase chain reaction (RT-PCR). 2 799 samples (18.8%) contained a respiratory virus. RSV was detected by IFA in 1 333 samples (8.9%). RSV was detected by RT-PCR in 192 samples from the RSV IFA-positive subgroup and in 25 samples from the RSV IFA-negative subgroup. hMPV was detected in eight samples from the RSV IFA-positive subgroup and in 11 samples from the RSV IFA-negative subgroup. Among the RSV infections, subtype A was dominant in two-year intervals, subtype B was dominant in one-year intervals. 85.3% of RSV and 74% of hMPV infections occurred in children younger than 5 years old. RSV and hMPV infections were associated with rainy seasons. Co-infection with RSV A and RSV B was detected in two patients. Five cases of co-infection with RSV and hMPV were detected. This report is the first to examine the epidemiology of ARIs in Colombia, with an emphasis on RSV and hMPV. The samples studied here were obtained over a 12-year period and represent all age groups and both genders.

  7. Post-extubation stridor in Respiratory Syncytial Virus bronchiolitis: Is there a role for prophylactic dexamethasone?

    Science.gov (United States)

    Veldhoen, Esther S; Smulders, Charlotte A; Kappen, Teus H; Calis, Job C; van Woensel, Job; Raymakers-Janssen, Paulien A M; Bont, Louis J; Hennus, Marije P

    2017-01-01

    The purpose of this study was to determine the incidence of reintubation due to upper airway obstruction in a homogeneous group of ventilated infants with Respiratory Syncytial Virus bronchiolitis. Our secondary objective was to determine whether prophylactic administration of dexamethasone prior to extubation was associated with decreased risk of reintubation. This retrospective observational study in two Pediatric Intensive Care Units in 2 university hospitals in The Netherlands included two hundred patients younger than 13 months admitted with respiratory insufficiency caused by Respiratory Syncytial Virus bronchiolitis, requiring invasive mechanical ventilation. A logistic regression analysis with propensity score method was used to adjust for possible confounding. Reintubation due to post-extubation stridor occurred in 17 (8.5%) of 200 patients. After propensity score matching, administration of dexamethasone prior to extubation was associated with a significantly (p = 0.0011) decreased risk of reintubation due to post-extubation stridor compared to patients not receiving prophylactic dexamethasone (absolute risk reduction 13%, 95% CI 5.3-21%). Reintubation due to post-extubation stridor is an important complication of ventilation for Respiratory Syncytial Virus bronchiolitis. Dexamethasone administered prior to extubation probably reduces the risk of post-extubation stridor necessitating reintubation in these infants. The results of this study support initiation of a placebo-controlled trial to confirm the beneficial effect of prophylactic dexamethasone.

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

    Science.gov (United States)

    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.

  9. Possible therapeutic effect of orally administered ribavirin for respiratory syncytial virus-induced acute respiratory distress syndrome in an immunocompetent patient: a case report.

    Science.gov (United States)

    Yoon, Byung Woo; Lee, Seung Hyeun

    2017-12-20

    Human respiratory syncytial virus usually causes self-limiting upper respiratory infection and occasionally causes pneumonia in immunocompromised hosts. Respiratory syncytial virus-induced severe pneumonia or acute respiratory distress syndrome in immunocompetent adults has been rarely described. Unfortunately, optimal treatment has not been established for this potentially fatal condition. We report a case of respiratory syncytial virus-induced acute respiratory distress syndrome occurring in a previously healthy man successfully treated with orally administered ribavirin. An 81-year-old previously healthy Korean man presented with cough, dyspnea, and febrile sensation. He had hypoxemia with diffuse ground glass opacity evident on chest radiography, which progressed and required mechanical ventilation. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of respiratory syncytial virus-induced acute respiratory distress syndrome, orally administered ribavirin was administered and he recuperated completely without complications. This case demonstrates the potential usefulness of orally administered ribavirin as a therapeutic option for severe respiratory syncytial virus infection, at least in an immunocompetent host.

  10. O polietilenoglicol aumenta a penetração do vírus da diarréia viral bovina, do vírus da estomatite vesicular e do vírus sincicial respiratório bovino em células de cultivo Polyethylene glycol increases the penetration of bovine viral diarrhea virus, vesicular stomatitis virus and bovine respiratory syncytial virus in cultured cells

    Directory of Open Access Journals (Sweden)

    Renata Dezengrini

    2009-06-01

    bovine enveloped viruses in culture cells. Penetration efficiency was measured by counting the number of viral plaques produced in bovine kidney cells (MDBK. The addition of 5% PEG (molecular weight 6.000 to the viral inoculum containing 100 TCID50 mL-1 (tissue culture median infectious dosis of each virus, during adsorption for 2h at 37°C, resulted in a significant increase in the number of plaques for bovine viral diarrhea virus (BVDV (increase of 3.4-fold, vesicular stomatitis virus (VSV (2.2-fold and bovine respiratory syncytial virus (BRSV (1.5-fold. The addition of 5% PEG to the inoculum of bovine herpesviruses 1, 2 and 5 (BoHV-1, BoHV-2 and BoHV-5 did not increase the number of viral plaques. On the other hand, PEG produced a reduction in the number of plaques by bovine parainfluenza virus (bPI-3V (1.4-fold. Furthermore, the addition of 5% PEG produced a 10- to 1000-fold increase in the sensitivity of BVDV detection in the serum of three persistently infected calves; and doubled the sensitivity of detection of BRSV in nasal secretions of two experimentally infected sheep. These results demonstrate that PEG enhances the efficiency of infection by BVDV, VSV and BRSV in cultured bovine cells and therefore may be used to increase the sensitivity of virus detection in clinical samples (viral isolation, and/or to increase virus titers in cell cultures.

  11. Respiratory syncytial virus shedding by children hospitalized with lower respiratory tract infection.

    Science.gov (United States)

    Takeyama, Aya; Hashimoto, Koichi; Sato, Masatoki; Kawashima, Ryoko; Kawasaki, Yukihiko; Hosoya, Mitsuaki

    2016-06-01

    Children with respiratory syncytial virus (RSV) infection shed virus for variable periods. The aim of this study was to quantify the viral load in nasopharyngeal aspirates of children with RSV throughout their hospitalization. This study included 37 children who were admitted with a diagnosis of RSV infection based on a positive rapid diagnostic test. Nasopharyngeal aspirates were collected from patients every day, from admission to discharge. Viral detection and quantification were performed using quantitative real-time PCR. Of the 37 patients, RSV-A was detected in 29 and RSV-B in 6. Two patients were PCR-negative for any type of RSV. RSV-A was detected in 12 of 16 patients (75%) 6 days after admission. These patients shed detectable virus from days 1 to 12, and for a significantly longer period (mean 5.7 days) than RSV-B (mean 3.8 days) patients. Half of the RSV-A patients were also positive on day 14 following onset. RSV-A was detected in patients infection. To prevent nosocomial RSV infections in hospital wards, healthcare workers must take appropriate infection control measures and provide adequate guidance on hand washing to the family of the patient. © 2015 Wiley Periodicals, Inc.

  12. Clinical Profiles of Respiratory Syncytial Virus Subtypes A AND B Among Children Hospitalized with Bronchiolitis.

    Science.gov (United States)

    Laham, Federico R; Mansbach, Jonathan M; Piedra, Pedro A; Hasegawa, Kohei; Sullivan, Ashley F; Espinola, Janice A; Camargo, Carlos A

    2017-08-01

    In this analysis of a prospective, multicenter study of children hospitalized with bronchiolitis, 925 had respiratory syncytial virus (RSV)-A and 649 had RSV-B. Overall, bronchiolitis severity did not differ by RSV subtype. However, among children with RSV-only bronchiolitis, those children with RSV-A had higher risk of intensive care treatment (odds ratio, 1.31; 95% confidence interval, 1.00-1.71; P = 0.048) when compared with those having RSV-B.

  13. Immune and inflammatory response in bronchiolitis due to respiratory Syncytial Virus and Rhinovirus infections in infants.

    Science.gov (United States)

    Vandini, Silvia; Calamelli, Elisabetta; Faldella, Giacomo; Lanari, Marcello

    2017-09-01

    Bronchiolitis is a common disease in infancy, mostly due to Respiratory Syncytial Virus and Rhinovirus. In addition to acute infection, viral bronchiolitis is responsible for sequelae including recurrent wheezing and asthma. The analysis of the viral characteristics and of the pathogenesis of the infection shows differences between the two viruses that may be helpful for the development of therapies and preventive strategies. Copyright © 2017. Published by Elsevier Ltd.

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

    OpenAIRE

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

    2014-01-01

    Background 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 resou...

  15. Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand.

    OpenAIRE

    Grimwood, K.; Cohet, C; Rich, FJ; Cheng, S.; Wood, C; Redshaw, N; Cunningham, CW; Pearce, N.; Kirman, JR

    2008-01-01

    This study assessed risk factors for respiratory syncytial virus (RSV) hospitalization and disease severity in Wellington, New Zealand. During the southern hemisphere winter months of 2003--2005, 230 infants aged < 24 months hospitalized with bronchiolitis were recruited. RSV was indentified in 141 (61%) infants. Comparison with data from all live hospital births from the same region (2003--2005) revealed three independent risk factors for RSV hospitalization: birth between February and July ...

  16. Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

    Directory of Open Access Journals (Sweden)

    Fonseca Claudia de Brito

    2003-01-01

    Full Text Available Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50% have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy, airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.

  17. Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

    Science.gov (United States)

    Fonseca, Claudia de Brito; Grisi, Sandra

    2003-01-01

    Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy), airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.

  18. Prematurity and the burden of influenza and respiratory syncytial virus disease.

    Science.gov (United States)

    Resch, Bernhard; Kurath-Koller, Stefan; Eibisberger, Monika; Zenz, Werner

    2016-02-01

    Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia (BPD) is high during infancy and early childhood. We performed a review based on a literature search including EMBASE, MEDLINE, and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant, prematurity, and BPD between 1980 and 2014. Recurrent respiratory symptoms remain common at preschool age, school age and even into young adulthood. Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the first years of life. Influenza virus infection plays a minor role compared to respiratory syncytial virus (RSV) associated respiratory tract infection during infancy and early childhood. Nevertheless, particular morbidity to both viruses is high. The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the first two years of life. Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months, and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.

  19. Clinical relevance of prevention of respiratory syncytial virus lower respiratory tract infection in preterm infants born between 33 and 35 weeks gestational age

    NARCIS (Netherlands)

    Carbonell-Estrany, X.; Bont, L.; Doering, G.; Gouyon, J-B; Lanari, M.

    2008-01-01

    Premature infants are vulnerable to severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) resulting in hospitalisation and the potential for longer-term respiratory morbidity. Whilst the severity and consequence of RSV LRTI are generally accepted and recognised in infants

  20. Simultaneous detection of respiratory syncytial virus types A and B ...

    African Journals Online (AJOL)

    Tharwat Ezzat Deraz

    2012-02-28

    Feb 28, 2012 ... Objectives: In this study, our aim was to determine the prevalence of influenza A and B, and. RSV types A and B ... Children's Hospital of the Ain Shams University due to severe lower respiratory tract infection. (LRTI). Clinical and .... children admitted to the hospital due to severe acute lower respiratory tract ...

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

    Science.gov (United States)

    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.

  2. Understanding respiratory syncytial virus (RSV) vaccine development and aspects of disease pathogenesis.

    Science.gov (United States)

    Jorquera, Patricia A; Anderson, Lydia; Tripp, Ralph A

    2016-01-01

    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infections causing bronchiolitis and some mortality in young children and the elderly. Despite decades of research there is no licensed RSV vaccine. Although significant advances have been made in understanding the immune factors responsible for inducing vaccine-enhanced disease in animal models, less information is available for humans. In this review, we discuss the different types of RSV vaccines and their target population, the need for establishing immune correlates for vaccine efficacy, and how the use of different animal models can help predict vaccine efficacy and clinical outcomes in humans.

  3. Risk factors for respiratory syncytial virus hospitalisation in children with heart disease

    DEFF Research Database (Denmark)

    Kristensen, K; Stensballe, L G; Bjerre, J

    2009-01-01

    hospitalisation predictors of the need for respiratory support (supplemental oxygen, nasal continuous positive airway pressure or mechanical ventilation) were young age (relative risk (RR) 0.47, 95% CI 0.32 to 0.67 per additional year of age) and cardiac decompensation (RR 1.81, 95% CI 1.02 to 3......OBJECTIVE: To assess the risk and risk factors for respiratory syncytial virus (RSV) hospitalisation and determinants of the severity of RSV disease in children with heart disease. METHODS: By using a database on RSV tests in Denmark all children with RSV diagnosed with heart disease in Denmark...

  4. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  5. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children.

    Science.gov (United States)

    Bisgaard, Hans; Flores-Nunez, Alejandro; Goh, Anne; Azimi, Parvin; Halkas, Andrew; Malice, Marie-Pierre; Marchal, Jean-Louis; Dass, S Balachandra; Reiss, Theodore F; Knorr, Barbara A

    2008-10-15

    A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus (RSV) bronchiolitic respiratory symptoms. To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. This was a double-blind study of 3- to 24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom-free days (%SFD; day with no daytime cough, wheeze, and shortness of breath, and no nighttime cough). No significant differences were seen between montelukast and placebo in %SFD over period I: mean +/- SD for placebo and for montelukast at 4 and 8 mg were 37.0 +/- 30.7, 38.6 +/- 30.4, and 38.5 +/- 29.9, respectively. Least-squares mean differences (95% confidence interval) between montelukast (4 mg) and placebo and between montelukast (8 mg) and placebo were 1.9% (-2.9, 6.7) and 1.6% (-3.2, 6.5), respectively. Secondary end points were similar across treatments. Both doses were generally well tolerated. During the first two treatment weeks, average %SFD was approximately 29%. In post hoc analyses of patients (n = 523) with persistent symptoms (%SFD bronchiolitis in children.

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

    Directory of Open Access Journals (Sweden)

    Flávio da Silva Mesquita

    Full Text Available Abstract Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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

    Science.gov (United States)

    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.

  8. Antibody responses in mice after immunization with inactivated bovine respiratory syncytial virus using different adjuvants Respostas de anticorpos em camundongos após imunização com vírus respiratório sincicial bovino inativado utilizando diferentes adjuvantes

    Directory of Open Access Journals (Sweden)

    Fernando Rosado Spilki

    2010-11-01

    Full Text Available Bovine respiratory syncytial virus (BRSV causes pneumonia in young cattle. Modified-live-virus (MLV and inactivated vaccines are currently used for the control of clinical effects of BRSV infections in cattle. On the present research, the stimulation of specific anti-BRSV immunoglobulin isotypes was investigated, through the use of different commercially available adjuvants (Water-in-oil emulsion, Quil A, Aluminum-hydroxide in inbred mice (Balb/C and C57BL/6. BRSV antibodies were measured using an enzyme-linked immunosorbent assay (ELISA and the results were compared to the antibody levels induced by immunization of animals using live-BRSV-virus. Water-in-oil emulsion and alum- adjuvant preparations induced higher levels of IgG1 immunoglobulins, whereas Quil A favored the production of IgG2 antibodies, this last being a more appropriate response profile for the specific case of BRSV. Not using adjuvants resulted in poor levels of specific antibodies. The isotype profile of specific antibodies obtained varied greatly depending on the adjuvants used. This information may be useful for the formulation of more effective BRSV inactivated vaccines; however, these findings have to be confirmed in cattle.O vírus respiratório sincicial bovino (BRSV causa pneumonia em bovinos jovens. Vacinas de vírus vivo modificado (MLV e vacinas inativadas são atualmente utilizadas para o controle dos efeitos clínicos de infecções pelo BRSV em bovinos. No presente trabalho, investigou-se a estimulação dos isotipos de imunoglobulinas específicas anti-BRSV, através da utilização de diferentes adjuvantes disponíveis comercialmente (água em óleo de emulsão, Quil A, hidróxido de alumínio em camundongos isogênicos (Balb/C e C57BL/6. Anticorpos contra o BRSV foram medidos usando-se um ensaio imunoenzimático (ELISA, e os resultados foram comparados com os níveis de anticorpos induzidos pela imunização de animais utilizando-se o BRSV vivo. As prepara

  9. Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ma. Del Rocío Baños-Lara

    2015-01-01

    Full Text Available Mucins (MUC constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV and human metapneumovirus (hMPV are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

  10. Host proteome correlates of vaccine-mediated enhanced disease in a mouse model of respiratory syncytial virus infection

    NARCIS (Netherlands)

    Diepen, A. van; Brand, H.K.; Waal, L. de; Bijl, M. van der; Jong, V.L.; Kuiken, T.; Amerongen, G. van; Ham, H.J. van den; Eijkemans, M.J.; Osterhaus, A.D.; Hermans, P.W.; Andeweg, A.C.

    2015-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and

  11. A Model of the Costs of Community and Nosocomial Pediatric Respiratory Syncytial Virus Infections in Canadian Hospitals

    Directory of Open Access Journals (Sweden)

    Philip Jacobs

    2013-01-01

    Full Text Available 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.

  12. Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection

    NARCIS (Netherlands)

    R.L. de Swart (Rik); T. Kuiken (Thijs); H.H. Timmerman (Helga); G. van Amerongen (Geert); B.G. van den Hoogen (Bernadette); H.W. Vos (Helma); H.J. Neijens (Herman); A.C. Andeweg (Arno); A.D.M.E. Osterhaus (Albert)

    2002-01-01

    textabstractRespiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. RSV vaccine development has been hampered by results of clinical trials in the 1960s, when formalin-inactivated whole-RSV preparations adjuvated with alum (FI-RSV) were found to

  13. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community

    NARCIS (Netherlands)

    Houben, M. L.; Coenjaerts, F. E. J.; Rossen, J. W. A.; Belderbos, M. E.; Hofland, R. W.; Kimpen, J. L. L.; Bont, L.

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral

  14. Transmission of respiratory syncytial virus at the paediatric intensive-care unit : A prospective study using real-time PCR

    NARCIS (Netherlands)

    van de Pol, A. C.; Rossen, J. W. A.; Wolfs, T. F. W.; Breteler, E. K.; Kimpen, J. L. L.; van Loon, A. M.; Jansen, N. J. G.

    Transmission of respiratory syncytial virus (RSV) from children with lower respiratory tract infection (LRTI) at a paediatric intensive-care unit (PICU) was examined using a highly sensitive real-time PCR. Twenty-four children with RSV LRTI were admitted during the study period (total days of

  15. [Risk factors for acute respiratory syncytial virus infection of lower respiratory tract in hospitalized infants].

    Science.gov (United States)

    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 infection were: GAinfection (OR = 1.351, 95%CI: 1.024-1.783; OR = 1.713, 95%CI: 1.332-2.204). Multivariate logistic regression determined the factors increasing the risk of RSV infection were: underlying CHD (OR = 1.298, 95%CI: 1.002-1.681), mother with atopic diseases (OR = 1.766, 95%CI: 1.237-2.520), autumn or winter infection (OR = 1.481, 95%CI: 1.105-1.985; OR = 1.766, 95%CI: 1.358-2.296). The prevalence of RSV infection was the highest in winter, while

  16. Computational Breakthrough of Natural Lead Hits from the Genus ofArisaemaagainst Human Respiratory Syncytial Virus.

    Science.gov (United States)

    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.

  17. EFFICACY AND SAFETY OF BAN HUANG ORAL LIQUID FOR TREATING BOVINE RESPIRATORY DISEASES.

    Science.gov (United States)

    Li, Bing; Zhou, Xu-Zheng; Niu, Jian-Rong; Wei, Xiao-Juan; Li, Jian-Yong; Yang, Ya-Jun; Liu, Xi-Wang; Cheng, Fu-Sheng; Zhang, Ji-Yu

    2017-01-01

    Ban Huang oral liquid was developed as a veterinary compound preparation by the Lanzhou Institute of Husbandry and Pharmaceutical Sciences of the Chinese Academy of Agricultural Sciences (CAAS). The purpose of this study was to determine whether the oral liquid preparation of traditional Chinese medicine, Ban Huang, is safe and effective for treating respiratory diseases in cattle. Acute oral toxicity experiments were conducted in Wistar rats and Kunming mice via oral administration. The minimum inhibitory concentration of the drug against Mycoplasma bovis in vitro with the double dilution method was 500 mg/mL, indicating good sensitivity. The results of laboratory pathogen testing, analysis of clinical symptoms, and analysis of pathological anatomy were combined to diagnose bovine respiratory diseases in 147 Simmental cattle caused by mixed infections of M. bovis , bovine respiratory syncytial virus, bovine parainfluenza virus type 3, and Mannheimia haemolytica . These cattle were randomly divided into three groups: drug treatment group 1 (treated via Tilmicosin injection), drug treatment group 2 (treated with Shuang Huang Lian oral liquid combined with Tilmicosin injection), and drug treatment group 3 (treated with Ban Huang oral liquid combined with Tilmicosin injection). Treatment effects were observed within 7 days. The results showed no toxicity and a maximum tolerated dose greater than 20 g/kg BW. For the 87 cattle in drug-treatment group, the cure rate was 90.80%, whereas the response rate was 94.25%. The cure rate of drug treatment group was increased by 14.13% in comparison with that of drug control group 1 and by 7.47% in comparison with that of drug control group 2 (both P bovine respiratory diseases, especially for mixed infection caused by M. bovis , bacteria, and viruses.

  18. Duration of immunity of a four-valent vaccine against bovine respiratory diseases

    Directory of Open Access Journals (Sweden)

    Corinne Philippe-Reversat

    2017-01-01

    Full Text Available This study demonstrated the duration of immunity over 6 months of a vaccine against key bovine respiratory disease pathogens: Parainfluenza 3, Bovine Respiratory Syncytial Virus, Bovine Viral Diarrhoea and Mannheimia haemolytica. This was performed by challenge on colostrum-deprived calves at the age of 2 weeks. Recent European field isolates were used as challenge strains. Clinical signs and pathogen excretion or presence were monitored. Field relevance of the viral challenge strains was analysed using phylogenic analysis. Significant reduction of excretion of the 3 viruses in vaccinated animals was a consistent finding, demonstrating the efficacy of the vaccine. Reducing shedding is indeed key to interrupting the infection transmission chain and helping to achieve the protective effects of immunisation that extend beyond the individual. A significant reduction of clinical signs and lung lesions following the Mannheimia haemolytica challenge was also observed in vaccinated animals versus controls. Comparison of the challenge strains to an array of global and European strains, including recent ones, demonstrated a high genetic proximity, supporting the potential for the vaccine to maintain similar levels of efficacy in the field over a 6-month period post vaccination.

  19. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

    Science.gov (United States)

    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

  20. Respiratory Syncytial Virus Increases the Virulence of Streptococcus pneumoniae by Binding to Penicillin Binding Protein 1a A New Paradigm in Respiratory Infection

    NARCIS (Netherlands)

    Smith, Claire M.; Sandrini, Sara; Datta, Sumit; Freestone, Primrose; Shafeeq, Sulman; Radhakrishnan, Priya; Williams, Gwyneth; Glenn, Sarah M.; Kuipers, Oscar P.; Hirst, Robert A.; Easton, Andrew J.; Andrew, Peter W.; O'Callaghan, Christopher

    2014-01-01

    Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. ObjeOtives: Todetermine if interaction between RSV

  1. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease : A randomized equivalence trial

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Woensel, Job B. M.; Uijtendaal, Esther; Uiterwaal, Cuno S. P. M.; Kimpen, Jan L. L.

    Background: Nearly halt of all hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral) antibiotics. The present study was designed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of

  2. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

    OpenAIRE

    Shi, Ting; McAllister, David A.; O'Brien, Katherine L.; Simoes, Eric A. F.; Madhi, Shabir A.; Gessner, Bradford D.; Polack, Fernando P.; Balsells, Evelyn; Acácio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Nicol, Mark P.; Nokes, D. James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza

    2017-01-01

    BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerabl...

  3. Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children

    DEFF Research Database (Denmark)

    von Linstow, M-L; Eugen-Olsen, J; Koch, A

    2006-01-01

    BACKGROUND: As respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause serious respiratory tract infections, the routes of transmission of these viruses are important to elucidate. We examined the modes of virus shedding and shedding duration of RSV and hMPV in young children...... of the infected children showed to have an upper respiratory tract infection when following up. CONCLUSION: Viral RNA was present in nasal secretions, saliva, sweat, and faeces, but whether or not the virions were infectious and constitute a potential mode of transmission remains to be shown in future studies........ METHODS: From each child in a group of 44 children (37 RSV-positive, 6 hMPV-positive, and 1 co-infected child), aged between 0.5-38 months, hospitalised at Hvidovre Hospital, Copenhagen, Denmark, one nasopharyngeal aspirate (NPA), saliva, urine, and faeces sample were collected at inclusion and weekly...

  4. Premature infants have impaired airway antiviral IFNγ responses to human metapneumovirus compared to respiratory syncytial virus.

    Science.gov (United States)

    Pancham, Krishna; Perez, Geovanny F; Huseni, Shehlanoor; Jain, Amisha; Kurdi, Bassem; Rodriguez-Martinez, Carlos E; Preciado, Diego; Rose, Mary C; Nino, Gustavo

    2015-10-01

    It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (respiratory disease in children with history of prematurity.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 hospitalizations was 116.2 per 1,000 child-years (244.9 in infants with a birth weight hospitalization is high among pre-mature infants in Lima. PMID:25294617

  7. A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult

    Directory of Open Access Journals (Sweden)

    Aakriti Gupta

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

  8. Burden of influenza, respiratory syncytial virus, and other respiratory viruses and the completeness of respiratory viral identification among respiratory inpatients, Canada, 2003-2014.

    Science.gov (United States)

    Schanzer, Dena L; Saboui, Myriam; Lee, Liza; Nwosu, Andrea; Bancej, Christina

    2017-12-15

    A regression-based study design has commonly been used to estimate the influenza burden; however, these estimates are not timely and many countries lack sufficient virological data. Alternative approaches that would permit a timelier assessment of the burden, including a sentinel surveillance approach recommended by the World Health Organization (WHO), have been proposed. We aimed to estimate the hospitalization burden attributable to influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) and to assess both the completeness of viral identification among respiratory inpatients in Canada and the implications of adopting other approaches. Respiratory inpatient records were extracted from the Canadian Discharge Abstract Database from 2003 to 2014. A regression model was used to estimate excess respiratory hospitalizations attributable to influenza, RSV, and ORV by age group and diagnostic category and compare these estimates with the number with a respiratory viral identification. An estimated 33 (95% CI: 29, 38), 27 (95% CI: 22, 33), and 27 (95% CI: 18, 36) hospitalizations per 100 000 population per year were attributed to influenza, RSV, and ORV, respectively. An influenza virus was identified in an estimated 78% (95% CI: 75, 81) and 17% (95% CI: 15, 21) of respiratory hospitalizations attributed to influenza for children and adults, respectively, and 75% of influenza-attributed hospitalizations had an ARI diagnosis. Hospitalization rates with respiratory viral identification still underestimate the burden. Approaches based on acute respiratory case definitions will likely underestimate the burden as well, although each proposed method should be compared with regression-based estimates of influenza-attributed burden as a way of assessing their validity. © 2017 The World Health Organization. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.

  9. Molecular survey of infectious agents associated with bovine respiratory disease in a beef cattle feedlot in southern Brazil.

    Science.gov (United States)

    Headley, Selwyn A; Okano, Werner; Balbo, Luciana C; Marcasso, Rogério A; Oliveira, Thalita E; Alfieri, Alice F; Negri Filho, Luiz C; Michelazzo, Mariana Z; Rodrigues, Silvio C; Baptista, Anderson L; Saut, João Paulo E; Alfieri, Amauri A

    2018-03-01

    We investigated the occurrence of infectious pathogens during an outbreak of bovine respiratory disease (BRD) in a beef cattle feedlot in southern Brazil that has a high risk of developing BRD. Nasopharyngeal swabs were randomly collected from steers ( n = 23) and assessed for the presence of infectious agents of BRD by PCR and/or RT-PCR assays. These included: Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCoV), bovine viral diarrhea virus (BVDV), bovine alphaherpesvirus 1 (BoHV-1), and bovine parainfluenza virus 3 (BPIV-3). Pulmonary sections of one steer that died with clinical BRD were submitted for pathology and molecular testing. The frequencies of the pathogens identified from the nasopharyngeal swabs were: H. somni 39% (9 of 23), BRSV 35% (8 of 23), BCoV 22% (5 of 23), and M. haemolytica 13% (3 of 23). PCR or RT-PCR assays did not identify P. multocida, M. bovis, BoHV-1, BVDV, or BPIV-3 from the nasopharyngeal swabs. Single and concomitant associations of infectious agents of BRD were identified. Fibrinous bronchopneumonia was diagnosed in one steer that died; samples were positive for H. somni and M. haemolytica by PCR. H. somni, BRSV, and BCoV are important disease pathogens of BRD in feedlot cattle in Brazil, but H. somni and BCoV are probably under-reported.

  10. Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

    Science.gov (United States)

    Grissett, G P; White, B J; Larson, R L

    2015-01-01

    Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Seroepidemiological study of bovine respiratory viruses (BRSV, BoHV-1, PI-3V, BVDV, and BAV-3) in dairy cattle in central region of Iran (Esfahan province).

    Science.gov (United States)

    Shirvani, Edris; Lotfi, Mohsen; Kamalzadeh, Morteza; Noaman, Vahid; Bahriari, Masumeh; Morovati, Hasan; Hatami, Alireza

    2012-01-01

    Respiratory diseases in calves are responsible for major economic losses in both beef and dairy production. Several viruses, such as bovine respiratory syncytial virus (BRSV), bovine herpes virus-1 (BoHV-1), bovine parainfluenza virus-3 (BPI-3V), bovine viral diarrhea virus (BVDV), and bovine adenoviruses (BAV), are detected in most clinical cases with respiratory signs. The aim of this study is to define seroprevalences of five major viral causes of bovine respiratory infections in cattle in central region of Iran (Esfahan province). The population targeted was 642 dairy cows (Holstein-Friesian) from 25 farms. Samples of blood serum from female cattle were examined. Sera were tested by commercial ELISA kits to detect antibody against BRSV, BoHV-1, BPI-3V, BVDV, and BAV-3. The results were analyzed by Chi-square test. In the present study, seroprevalences of BRSV, BoHV-1, PI3V, BVDV, and BAV-3 were 51.1%, 72%, 84.4%, 49.2%, and 55.6%, respectively. The present study shows that infections of bovine respiratory viruses are very common in cattle in Esfahan.

  12. Bovine coronaviruses from the respiratory tract: Antigenic and genetic diversity

    Science.gov (United States)

    Bovine corona viruses (BoCV) isolated from respiratory tract, nasal swab and broncho alveolar washing fluid samples were evaluated for genetic and antigenic differences. These BoCV from the respiratory tract of healthy and clinically ill cattle with BRD signs were compared to reference and vaccine ...

  13. Supplemental Oxygen-Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus.

    Science.gov (United States)

    Waghmare, Alpana; Xie, Hu; Kimball, Louise; Yi, Jessica; Özkök, Sezen; Leisenring, Wendy; Cheng, Guang-Shing; Englund, Janet A; Watkins, Timothy R; Chien, Jason W; Boeckh, Michael

    2017-12-05

    Clinically meaningful endpoints for respiratory syncytial virus (RSV) treatment trials are lacking for hematopoietic cell transplant (HCT) recipients. We evaluated supplemental oxygen use among HCT recipients with RSV infection. Subjects were grouped according to the presence of upper respiratory tract infection (URTI) without lower respiratory tract infection (LRTI), URTI progressing to LRTI, and LRTI at presentation. LRTI was defined as a positive lower respiratory tract sample with or without radiographic abnormality (defined as proven or probable LRTI, respectively) or a positive upper respiratory tract sample with radiographic abnormality (possible LRTI). Supplemental oxygen-free days were defined as any day while alive after diagnosis of RSV infection during which ≤2 L of supplemental oxygen per minute was received. Among 230 patients, supplemental oxygen use by day 28 after the first diagnosis of RSV infection was lowest in patients presenting with URTI (31 of 197 [16%]). Supplemental oxygen use was lower in patients with possible LRTI (12 of 45 [27%]) than in those with proven/probable LRTI (29 of 42 [69%]). Patients presenting with proven/probable LRTI had a median of 16 fewer supplemental oxygen-free days than those presenting with URTI (P respiratory tract provides prognostic information that may help prioritize therapies. Supplemental oxygen-free days as a clinical endpoint may allow smaller sample sizes for trials evaluating RSV antivirals.

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

    Science.gov (United States)

    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.

  15. Visualizing the replication of respiratory syncytial virus in cells and in living mice.

    Science.gov (United States)

    Rameix-Welti, Marie-Anne; Le Goffic, Ronan; Hervé, Pierre-Louis; Sourimant, Julien; Rémot, Aude; Riffault, Sabine; Yu, Qin; Galloux, Marie; Gault, Elyanne; Eléouët, Jean-François

    2014-10-03

    Respiratory syncytial virus (RSV) is the most important cause of severe lower-respiratory tract disease in calves and young children, yet no human vaccine nor efficient curative treatments are available. Here we describe a recombinant human RSV reverse genetics system in which the red fluorescent protein (mCherry) or the firefly luciferase (Luc) genes are inserted into the RSV genome. Expression of mCherry and Luc are correlated with infection rate, allowing the monitoring of RSV multiplication in cell culture. Replication of the Luc-encoding virus in living mice can be visualized by bioluminescent imaging, bioluminescence being detected in the snout and lungs of infected mice after nasal inoculation. We propose that these recombinant viruses are convenient and valuable tools for screening of compounds active against RSV, and can be used as an extremely sensitive readout for studying effects of antiviral therapeutics in living mice.

  16. Respiratory syncytial virus hospitalization and mortality: Systematic review and meta‐analysis

    Science.gov (United States)

    Stein, Renato T.; Bont, Louis J.; Zar, Heather; Polack, Fernando P.; Park, Caroline; Claxton, Ami; Borok, Gerald; Butylkova, Yekaterina

    2016-01-01

    Summary Background: Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally. Methods: Systematic literature review and meta‐analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV‐ARI and death. Results: Five thousand two hundred and seventy‐four references were identified. Fifty‐five studies were included from 32 countries. The global RSV‐ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children Wiley Periodicals, Inc. PMID:27740723

  17. Synthetic Biodegradable Microparticle and Nanoparticle Vaccines against the Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Patricia A. Jorquera

    2016-12-01

    Full Text Available Synthetic biodegradable microparticle and nanoparticle platform technology provides the opportunity to design particles varying in composition, size, shape and surface properties for application in vaccine development. The use of particle vaccine formulations allows improvement of antigen stability and immunogenicity while allowing targeted delivery and slow release. This technology has been design to develop novel vaccines against the respiratory syncytial virus (RSV, the leading cause of lower respiratory tract infection in infants. In the last decade, several nano- and micro-sized RSV vaccine candidates have been developed and tested in animal models showing promising results. This review provides an overview of recent advances in prophylactic particle vaccines for RSV and the multiple factors that can affect vaccine efficacy.

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

    DEFF Research Database (Denmark)

    Sørup, Signe; Benn, Christine Stabell; Stensballe, Lone Graff

    2015-01-01

    BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: The study...

  19. A Decade of Respiratory Syncytial Virus Epidemiology and Prophylaxis: Translating Evidence into Everyday Clinical Practice

    Directory of Open Access Journals (Sweden)

    Bosco A Paes

    2011-01-01

    Full Text Available 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.

  20. In Hot Pursuit of the First Vaccine Against Respiratory Syncytial Virus.

    Science.gov (United States)

    Kim, Joo Young; Chang, Jun

    2016-07-01

    Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection, such as bronchiolitis, bronchitis, or pneumonia, in both infants and the elderly. Despite the global burden of diseases attributable to RSV infection, no clinically approved vaccine is available, and a humanized monoclonal antibody for prophylaxis is not readily affordable in developing countries. There are several hurdles to the successful development of RSV vaccines: immune-vulnerable target populations such as premature infants, pregnant women, and immunocompromised people; safety concerns associated with vaccine-enhanced diseases; repeated infection; and waning memory. To develop successful strategies for the prevention of RSV infection, it is necessary to understand the protective and pathologic roles of host immune responses to RSV infection. In this review, we will summarize the positive and negative relationship between RSV infection and host immunity and discuss strategies for the development of the first successful RSV vaccine.

  1. Genotypes and clinical data of respiratory syncytial virus and metapneumovirus in brazilian infants: a new perspective

    Directory of Open Access Journals (Sweden)

    Adriana Gut Lopes Riccetto

    Full Text Available The aim of this study was to determine if there was a correlation between respiratory syncytial virus (RSV and metapneumovirus (MPV genotypes and clinical data of Brazilian infants hospitalized for acute lower respiratory infection. The viruses in the patients' nasopharyngeal secretions were studied using the polymerase chain reaction and phylogenetic analysis. The study assessed 144 infants; 31.9% were RSV positive and 5.6% were MPV positive. Statistical analysis was performed using the chi-squared test, Fisher's test, Odds ratio, univariate logistic regression, non-conditional multivariate logistic regression and the forward - stepwise method. Multivariate analysis confirmed a significant relationship between a positive PCR test for RSV and hospitalization during the month of May and with pulse oximetry less than 90%. The phylogenetic analysis indicated the genotypes GA2, GA5, SAA1 (Group A, SAB1, SAB3 and BA (Group B for RSV and Group B, subgroup B1, for MPV.

  2. Drug candidates and model systems in respiratory syncytial virus antiviral drug discovery.

    Science.gov (United States)

    Heylen, Elisabeth; Neyts, Johan; Jochmans, Dirk

    2017-03-01

    The development of antiviral strategies to prevent or treat respiratory syncytial virus (RSV) infections is of great importance, especially considering the fact that RSV is one of the most important causes of pediatric respiratory infections. However, despite intense efforts, there is no antiviral or vaccine approved for the prevention or treatment of RSV infections. Several inhibitors, targeting different RSV proteins have been discovered over the past decade. We here review the most important chemical series as well as recent developments in understanding which viral proteins and/or host cell factors are good targets for inhibition of viral replication. In addition, we highlight the current in vitro and in vivo model systems of the disease. A number of molecules are currently in (advanced) preclinical or clinical development. Significant breakthroughs in the field may be expected in the upcoming years. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Rapid spread and diversification of respiratory syncytial virus genotype ON1, Kenya.

    Science.gov (United States)

    Agoti, Charles N; Otieno, James R; Gitahi, Caroline W; Cane, Patricia A; Nokes, D James

    2014-06-01

    Respiratory syncytial virus genotype ON1, which is characterized by a 72-nt duplication in the attachment protein gene, has been detected in >10 countries since first identified in Ontario, Canada, in 2010. We describe 2 waves of genotype ON1 infections among children admitted to a rural hospital in Kenya during 2012. Phylogenetic analysis of attachment protein gene sequences showed multiple introductions of genotype ON1; variants distinct from the original Canadian viruses predominated in both infection waves. The genotype ON1 dominated over the other group A genotypes during the second wave, and some first wave ON1 variants reappeared in the second wave. An analysis of global genotype ON1 sequences determined that this genotype has become considerably diversified and has acquired signature coding mutations within immunogenic regions, and its most recent common ancestor dates to ≈2008-2009. Surveillance of genotype ON1 contributes to an understanding of the mechanisms of rapid emergence of respiratory viruses.

  4. Recent Advances in Diagnosis, Prevention, and Treatment of Human Respiratory Syncytial Virus

    Science.gov (United States)

    Bawage, Swapnil Subhash; Tiwari, Pooja Munnilal; Singh, Shree Ram

    2013-01-01

    Human respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and the elderly, leading to significant morbidity and mortality. The interdisciplinary fields, especially biotechnology and nanotechnology, have facilitated the development of modern detection systems for RSV. Many anti-RSV compounds like fusion inhibitors and RNAi molecules have been successful in laboratory and clinical trials. But, currently, there are no effective drugs for RSV infection even after decades of research. Effective diagnosis can result in effective treatment, but the progress in both of these facets must be concurrent. The development in prevention and treatment measures for RSV is at appreciable pace, but the implementation into clinical practice still seems a challenge. This review attempts to present the promising diverse research approaches and advancements in the area of diagnosis, prevention, and treatment that contribute to RSV management. PMID:24382964

  5. Evaluation of an alternative chest physiotherapy method in infants with respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Postiaux, Guy; Louis, Jacques; Labasse, Henri C; Gerroldt, Julien; Kotik, Anne-Claire; Lemuhot, Amandine; Patte, Caroline

    2011-07-01

    We proposed a new chest physiotherapy (CPT) secretion clearance method to treat respiratory syncytial virus bronchiolitis in infants. Our new CPT method consists of 15 prolonged slow expirations, then 5 provoked cough maneuvers. We randomized 20 infants (mean age 4.2 months) into 2 groups: 8 patients received 27 sessions of nebulization of hypertonic saline; 12 patients received 31 sessions of nebulization of hypertonic saline followed by our new CPT method. We used the Wang clinical severity scoring system (which assesses wheezing, respiratory rate, retractions, and general condition) and measured S(pO(2)) and heart rate before each CPT session (T0), immediately after the 30-min session (T30), and 120 min after the session (T150). Within the groups: in the first group, Wang score was significantly lower at T150 than at T0: 4.6 vs 5.0 (P = .008). In the new-method-CPT group, Wang score was significantly lower at T30 (3.6 vs 4.3, P = .001) and at T150 (3.7 vs 4.3, P = .002). Wheezing score was significantly lower at T150 than at T0 (1.1 vs 1.2, P = .02) in the first group, and in the new-method-CPT group at T30 than at T0 (0.8 vs 1.3, P = .001) and at T150 than at T0 (0.9 vs 1.3, P = .001). Between the groups: at T30 the improvement was significantly better in the new-method-CPT group for overall Wang score (P = .02), retractions (P = .05), respiratory rate (P = .001), and heart rate (P infants with acute respiratory syncytial virus bronchiolitis.

  6. Efficacy and safety of Ban Huang oral liquid for treating bovine ...

    African Journals Online (AJOL)

    The results of laboratory pathogen testing, analysis of clinical symptoms, and analysis of pathological anatomy were combined to diagnose bovine respiratory diseases in 147 Simmental cattle caused by mixed infections of M. bovis, bovine respiratory syncytial virus, bovine parainfluenza virus type 3, and Mannheimia ...

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

    Science.gov (United States)

    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.

  8. Associations between exposure to viruses and bovine respiratory disease in Australian feedlot cattle.

    Science.gov (United States)

    Hay, K E; Barnes, T S; Morton, J M; Gravel, J L; Commins, M A; Horwood, P F; Ambrose, R C; Clements, A C A; Mahony, T J

    2016-05-01

    Bovine respiratory disease (BRD) is the most important cause of clinical disease and death in feedlot cattle. Respiratory viral infections are key components in predisposing cattle to the development of this disease. To quantify the contribution of four viruses commonly associated with BRD, a case-control study was conducted nested within the National Bovine Respiratory Disease Initiative project population in Australian feedlot cattle. Effects of exposure to Bovine viral diarrhoea virus 1 (BVDV-1), Bovine herpesvirus 1 (BoHV-1), Bovine respiratory syncytial virus (BRSV) and Bovine parainfluenza virus 3 (BPIV-3), and to combinations of these viruses, were investigated. Based on weighted seroprevalences at induction (when animals were enrolled and initial samples collected), the percentages of the project population estimated to be seropositive were 24% for BoHV-1, 69% for BVDV-1, 89% for BRSV and 91% for BPIV-3. For each of the four viruses, seropositivity at induction was associated with reduced risk of BRD (OR: 0.6-0.9), and seroincrease from induction to second blood sampling (35-60 days after induction) was associated with increased risk of BRD (OR: 1.3-1.5). Compared to animals that were seropositive for all four viruses at induction, animals were at progressively increased risk with increasing number of viruses for which they were seronegative; those seronegative for all four viruses were at greatest risk (OR: 2.4). Animals that seroincreased for one or more viruses from induction to second blood sampling were at increased risk (OR: 1.4-2.1) of BRD compared to animals that did not seroincrease for any viruses. Collectively these results confirm that prior exposure to these viruses is protective while exposure at or after feedlot entry increases the risk of development of BRD in feedlots. However, the modest increases in risk associated with seroincrease for each virus separately, and the progressive increases in risk with multiple viral exposures highlights

  9. Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity.

    Science.gov (United States)

    Hendricks, Matthew R; Lashua, Lauren P; Fischer, Douglas K; Flitter, Becca A; Eichinger, Katherine M; Durbin, Joan E; Sarkar, Saumendra N; Coyne, Carolyn B; Empey, Kerry M; Bomberger, Jennifer M

    2016-02-09

    Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients' acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.

  10. ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CHILDREN IN THE AGE ASPECT

    Directory of Open Access Journals (Sweden)

    V. B. Rovny

    2013-01-01

    Full Text Available The clinical features of laboratory-confirmed acute respiratory syncytial virus infection (ARSVI are described in 221 children of the age from 1 month to 5 years. Febrile fever has been recorded in 76% of patients with ARSVI, and significantly more often in children in the second year of life (92%, but the difference in the temerature or duration has not been found. 98% of children have had symptoms of the lower respiratory tract lesions. The most common ARSVI manifestations in the patients of the first year of life were obstructive diseases of the lower respiratory tract (obstructive bronchitis in 53% and bronchiolitis in 11% of children, in the patients of the second year of life — pneumonia (28%, p < 0,05 and catarrhal otitis (26%; p < 0,05. Bronchial obstruction syndrome in children of the first year of life was characterized by the significantly higher frequency (73% and the maximal duration (9,7 ± 1,08 days. The largest number of cases of the severe respiratory failure has been recorded among patients of the second year of life (3 degree of respiratory failure in 22% of patients, p < 0,05.

  11. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Congenital Heart Disease

    NARCIS (Netherlands)

    Checchia, Paul A; Paes, Bosco; Bont, Louis; Manzoni, Paolo; Simões, Eric A F; Fauroux, Brigitte; Figueras-Aloy, Josep; Carbonell-Estrany, Xavier

    INTRODUCTION: The REGAL (RSV Evidence-a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This fourth publication covers the risk and burden of RSV

  12. Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection.

    NARCIS (Netherlands)

    A.H. Brandenburg (Afke); J. Groen (Jan); H.A. Moll (Henriëtte); E.C.J. Claas (Eric); Ph.H. Rothbarth (Philip); H.J. Neijens (Herman); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractThe decline of maternal respiratory syncytial virus (RSV) specific serum antibodies was studied in 45 children during the first 6 months of life, using a virus neutralization assay and competition ELISAs measuring fusion protein and glycoprotein specific antibodies. In all children RSV

  13. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study

    NARCIS (Netherlands)

    Blanken, M.O.; Koffijberg, H.; Nibbelke, E.E.; Rovers, M.M.; Bont, L.; Liem, K.D.

    2013-01-01

    OBJECTIVES: This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33-35 weeks gestational age (WGA). STUDY DESIGN: The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were

  14. The impact of laboratory characteristics on molecular detection of respiratory syncytial virus in a European multicentre quality control study

    NARCIS (Netherlands)

    Meerhoff, T. J.; MacKay, W. G.; Meijer, A.; Paget, W. J.; Niesters, H. G. M.; Kimpen, J. L. L.; Schellevis, F.

    2008-01-01

    The performance of nucleic acid amplification techniques for detecting respiratory syncytial virus (RSV) was evaluated in 25 laboratories across Europe by an external quality assessment study. In addition, factors related to the diagnostic performance of laboratories were explored. The results of

  15. The impact of laboratory characteristics on molecular detection of respiratory syncytial virus in a European multicentre quality control study.

    NARCIS (Netherlands)

    Meerhoff, T.J.; MacKay, W.G.; Meijer, A.; Paget, W.J.; Niesters, H.G.M.; Kimpen, J.L.L.; Schellevis, F.

    2008-01-01

    The performance of nucleic acid amplification techniques for detecting respiratory syncytial virus (RSV) was evaluated in 25 laboratories across Europe by an external quality assessment study. In addition, factors related to the diagnostic performance of laboratories were explored. The results of

  16. Intranasal administration of antibody-bound respiratory syncytial virus particles efficiently primes virus-specific immune responses in mice

    NARCIS (Netherlands)

    Kruijsen, Debby; Einarsdottir, Helga K.; Schijf, Marcel A.; Coenjaerts, Frank E.; van der Schoot, Ellen C.; Vidarsson, Gestur; van Bleek, Grada M.

    2013-01-01

    Infants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to

  17. Infants with severe respiratory syncytial virus needed less ventilator time with nasal continuous airways pressure then invasive mechanical ventilation

    NARCIS (Netherlands)

    Borckink, Ilse; Essouri, Sandrine; Laurent, Marie; Albers, Marcel J. I. J.; Burgerhof, Johannes G. M.; Tissieres, Pierre; Kneyber, Martin C. J.

    AIM: Nasal continuous positive airway pressure (NCPAP) has been proposed as an early first-line support for infants with severe respiratory syncytial virus (RSV) infection. We hypothesised that infants <6 months with severe RSV would require shorter ventilator support on NCPAP than invasive

  18. Defining the Epidemiology and Burden of Severe Respiratory Syncytial Virus Infection Among Infants and Children in Western Countries

    NARCIS (Netherlands)

    Bont, Louis|info:eu-repo/dai/nl/304813370; Checchia, Paul A; Fauroux, Brigitte; Figueras-Aloy, Josep; Manzoni, Paolo; Paes, Bosco; Simões, Eric A F; Carbonell-Estrany, Xavier

    INTRODUCTION: The REGAL (RSV [respiratory syncytial virus] Evidence-a Geographical Archive of the Literature) series provides a comprehensive review of the published evidence in the field of RSV in Western countries over the last 20 years. This first of seven publications covers the epidemiology and

  19. T-CELL REDISTRIBUTION KINETICS AFTER SECONDARY INFECTION OF BALB/C MICE WITH RESPIRATORY SYNCYTIAL VIRUS

    NARCIS (Netherlands)

    KIMPEN, JLL; OGRA, PL

    BALB/c mice were infected intranasally with live respiratory syncytial virus (RSV) and reinfected 4 weeks later. At regular intervals thereafter groups of animals were killed and T cell subsets were determined in blood, spleen and bronchoalveolar lavage (BAL) with flow cytometry employing T cell

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

    Science.gov (United States)

    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,...

  1. Association of bovine respiratory disease or vaccination with serologic response in dairy heifer calves up to three months of age.

    Science.gov (United States)

    Windeyer, M Claire; Leslie, Ken E; Godden, Sandra M; Hodgins, Douglas C; Lissemore, Kerry D; LeBlanc, Stephen J

    2015-03-01

    To investigate the association of bovine respiratory disease (BRD) or vaccination with serologic response in calves. 94 Holstein calves. To assess the association between BRD and antibody titers, 38 calves bovine respiratory syncytial virus (BRSV), bovine viral diarrhea virus types 1 and 2, bovine herpesvirus type 1 (BHV1), and parainfluenza virus type 3 at 2 weeks of age (n = 6), 5 weeks of age (6), and both 2 and 5 weeks of age (6) or were assigned to be unvaccinated controls (6). Blood samples were obtained at I, 2, 5, and 12 weeks for determination of serum neutralization antibody titers against the vaccine viruses, bovine coronavirus, and Mannheimia haemolytica. Antibody rates of decay were calculated. Calves with initial antibody titers against BRSV < 1:64 that were treated for BRD had a slower rate of anti-BRSV antibody decay than did similar calves that were not treated for BRD. Calves with high initial antibody titers against BRSV and BHV1 had lower odds of BRD than did calves with low initial antibody titers against those 2 pathogens. Vaccination at 2 or 5 weeks of age had no effect on the rate of antibody decay. Clinical BRD and the serologic response of dairy calves were associated with initial antibody titers against BRSV and BHV1. Serologic or clinical responses to viral exposure may differ in calves with low passive immunity.

  2. Analysis of Respiratory Syncytial Virus in Clinical Samples by Reverse Transcriptase-Polymerase Chain Reaction Restriction Mapping

    OpenAIRE

    Valdivia, Angel; Savón, Clara; Chacón, Danay; Sarmiento, Luis; Morier, Luis; Otero, Anselmo; Soto, Yudira; Oropesa, Suset; Goyenechea, Angel

    1997-01-01

    The aim of this study was to develop a polymerase chain reaction (PCR) for the detection of respiratory syncytial virus (RSV) genomes. The primers were designed from published sequences and selected from conserved regions of the genome encoding for the N protein of subgroups A and B of RSV. PCR was applied to 20 specimens from children admitted to the respiratory ward of "William Soler" Pediatric Hospital in Havana City with a clinical diagnosis of bronchiolitis. The PCR was compared with vir...

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

    Science.gov (United States)

    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 respiratory pathogens including RSV in children 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 Respiratory Viruses Published by John Wiley & Sons Ltd.

  4. Is radiological appearance of lower respiratory tract infection due to respiratory syncytial virus a predictor of clinical outcome?

    Science.gov (United States)

    Alkan Ozdemir, Senem; Ozer, Esra Arun; Pekcevik, Yeliz; Ilhan, Ozkan; Sutcuoglu, Sumer

    2015-01-01

    Respiratory syncytial virus (RSV) lower respiratory tract infection is the most common viral infection in childhood. RSV-infected infants demonstrate various radiographic findings. The aim of the study is to evaluate whether assessment of radiological characteristics of lower tract infection due to RSV may be a predictor of clinical outcome in newborns. The study included 36 newborn infants hospitalized for lower tract infection. In order to detect RSV, RSV Respi-Strip (Coris Bioconcept Organization) test kits were used on admission. Chest X-rays and clinical characteristics of the study group were reviewed. Of 36 patients hospitalized for lower tract infection from October 2012 to April 2013, 18 (50%) newborns were infected with RSV. The study included 36 neonates. Patients with RSV-positive infants at admission had greater need for respiratory support, supplemental oxygen and prolonged stay in the NICU. Newborns with an atelectasis pattern on admission chest radiograph had greater at RSV-positive infants. Chest radiological patterns with lower respiratory tract infection in newborn infants due to RSV are a predictor of clinical outcome.

  5. Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Bruning, Andrea H L; Leeflang, Mariska M G; Vos, Johanna M B W; Spijker, Rene; de Jong, Menno D; Wolthers, Katja C; Pajkrt, Dasja

    2017-09-15

    Rapid diagnosis of respiratory virus infections contributes to patient care. This systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. We searched Medline and EMBASE for studies evaluating these tests against polymerase chain reaction as the reference standard. Of 179 studies included, 134 evaluated rapid tests for influenza viruses, 32 for respiratory syncytial virus (RSV), and 13 for other respiratory viruses. We used the bivariate random effects model for quantitative meta-analysis of the results. Most tests detected only influenza viruses or RSV. Summary sensitivity and specificity estimates of tests for influenza were 61.1% and 98.9%. For RSV, summary sensitivity was 75.3%, and specificity, 98.7%. We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Because of incomplete reporting, the risk of bias was often unclear. Despite their intended use at the point of care, 26.3% of tests were evaluated in a laboratory setting. Although newly developed tests seem more sensitive, high-quality evaluations of these tests are lacking. © 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.

  6. Genetic vaccine for respiratory syncytial virus provides protection without disease potentiation.

    Science.gov (United States)

    Johnson, Teresa R; Rangel, David; Graham, Barney S; Brough, Douglas E; Gall, Jason G

    2014-01-01

    Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥ 24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.

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

    Science.gov (United States)

    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.

  8. Preexposure to CpG protects against the delayed effects of neonatal respiratory syncytial virus infection.

    Science.gov (United States)

    Yamaguchi, Yuko; Harker, James A; Wang, Belinda; Openshaw, Peter J; Tregoning, John S; Culley, Fiona J

    2012-10-01

    Severe respiratory viral infection in early life is associated with recurrent wheeze and asthma in later childhood. Neonatal immune responses tend to be skewed toward T helper 2 (Th2) responses, which may contribute to the development of a pathogenic recall response to respiratory infection. Since neonatal Th2 skewing can be modified by stimulation with Toll-like receptor (TLR) ligands, we investigated the effect of exposure to CpG oligodeoxynucleotides (TLR9 ligands) prior to neonatal respiratory syncytial virus (RSV) infection in mice. CpG preexposure was protective against enhanced disease during secondary adult RSV challenge, with a reduction in viral load and an increase in Th1 responses. A similar Th1 switch and reduction in disease were observed if CpG was administered in the interval between neonatal infection and challenge. In neonates, CpG pretreatment led to a transient increase in expression of major histocompatibility complex class II (MHCII) and CD80 on CD11c-positive cells and gamma interferon (IFN-γ) production by NK cells after RSV infection, suggesting that the protective effects may be mediated by antigen-presenting cells (APC) and NK cells. We conclude that the adverse effects of early-life respiratory viral infection on later lung health might be mitigated by conditions that promote TLR activation in the infant lung.

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

    Science.gov (United States)

    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 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.

  10. Trends of Respiratory Syncytial Virus Infections in Children under 2 Years of Age in Puerto Rico.

    Science.gov (United States)

    Matías, Israel; García, Inés; García-Fragoso, Lourdes; Puig, Gilberto; Pedraza, Lourdes; Rodríguez, Luis; Santaella, Alvaro; Arce, Sylvia; Toledo, Marilyn; Soto, Edwin; Valcárcel, Marta

    2015-06-01

    The respiratory syncytial virus (RSV) is the most significant viral pathogen causing bronchiolitis and pneumonia in infants, today. In tropical climates the RSV infection may occur throughout the year. The purpose of this study was to asses RSV infections during the 2009‒2010 RSV season in children under 2 years of age and to evaluate the trend of positive RSV tests in the period of 2007 to 2009. A retrospective review of data collected from 6 hospitals in Puerto Rico was performed. Patients with confirmed RSV bronchiolitis were included in the study. A total of 4,678 patients were included. The mean age of the patients was 7 months. Data showed that RSV infection occurred throughout the studied months. Data confirms a year-round presence of RSV in Puerto Rico. The RSV surveillance system needs to be reinforced to establish and understand the epidemiology of RSV and to review the current immunoprophylaxis guidelines.

  11. The influence of diurnal temperature range on the incidence of respiratory syncytial virus in Japan.

    Science.gov (United States)

    Onozuka, D

    2015-03-01

    The incidence of respiratory syncytial virus (RSV) has been reported to exhibit seasonal variation. However, the impact of diurnal temperature range (DTR) on RSV has not been investigated. After acquiring data related to cases of RSV and weather parameters of DTR in Fukuoka, Japan, between 2006 and 2012, we used negative binomial generalized linear models and distributed lag nonlinear models to assess the possible relationship between DTR and RSV cases, adjusting for confounding factors. Our analysis revealed that the weekly number of RSV cases increased with a relative risk of 3·30 (95% confidence interval 1·65-6·60) for every 1°C increase in DTR. Our study provides quantitative evidence that the number of RSV cases increased significantly with increasing DTR. We suggest that preventive measures for limiting the spread of RSV should be considered during extended periods of high DTR.

  12. Systemic signature of the lung response to respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available Respiratory Syncytial Virus is a frequent cause of severe bronchiolitis in children. To improve our understanding of systemic host responses to RSV, we compared BALB/c mouse gene expression responses at day 1, 2, and 5 during primary RSV infection in lung, bronchial lymph nodes, and blood. We identified a set of 53 interferon-associated and innate immunity genes that give correlated responses in all three murine tissues. Additionally, we identified blood gene signatures that are indicative of acute infection, secondary immune response, and vaccine-enhanced disease, respectively. Eosinophil-associated ribonucleases were characteristic for the vaccine-enhanced disease blood signature. These results indicate that it may be possible to distinguish protective and unfavorable patient lung responses via blood diagnostics.

  13. Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette

    2004-01-01

    A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently to human beta2-microglobulin (beta2m). Cutaneous gene...... elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the beta2m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion...... of CD8+ T cells reduced, but did not abolish, enhancement of disease. Mice vaccinated with a construct encoding a class I-restricted lymphocytic choriomeningitis virus epitope and beta2m suffered more severe weight loss after RSV infection than unvaccinated RSV-infected mice, although RSV-specific CD8...

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

    Science.gov (United States)

    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.

  15. Seasonality of respiratory syncytial virus in Buenos Aires. Relationship with global climate change.

    Science.gov (United States)

    Ferrero, Fernando; Torres, Fernando; Abrutzky, Rosana; Ossorio, María F; Marcos, Alejandra; Ferrario, Claudia; Rial, María J

    2016-02-01

    Global climate change circulation pattern respiratory syncytial virus (RSV). We assessed whether RSV season has changed over the past 20 years and its correlation with mean annual temperature. Cross-sectional study that included records of RSV and temperatures from Buenos Aires (1995-2014). RSV season onset, offset and duration, and its correlation with mean annual temperature were described for each year. A total of 8109 RSV infections were identified. The duration of RSV season reduced significantly (1995: 29 weeks vs. 2014: 17 weeks; R: 0.6; p < 0.001) due to an early ending (1995: week 45 vs. 2014: week 33; R: 0.6; p < 0.001). No correlation was observed between mean annual temperature and RSV season start, end and duration. Over the past 20 years, RSV season shortened significantly, but no correlation with temperature was observed. Sociedad Argentina de Pediatría.

  16. Structural, antigenic and immunogenic features of respiratory syncytial virus glycoproteins relevant for vaccine development

    Science.gov (United States)

    Melero, José A.; Mas, Vicente; McLellan, Jason S.

    2016-01-01

    Extraordinary progress in the structure and immunobiology of the human respiratory syncytial virus glycoproteins has been accomplished during the last few years. Determination of the fusion (F) glycoprotein structure folded in either the prefusion or the postfusion conformation was an inspiring breakthrough not only to understand the structural changes associated with the membrane fusion process but additionally to appreciate the antigenic intricacies of the F molecule. Furthermore, these developments have opened new avenues for structure-based designs of promising hRSV vaccine candidates. Finally, recent advances in our knowledge of the attachment (G) glycoprotein and its interaction with cell-surface receptors have revitalized interest in this molecule as a vaccine, as well as its role in hRSV immunobiology. PMID:27692522

  17. Infection expérimentale de veaux par le virus respiratoire syncytial bovin : évaluation de la persistance virale

    OpenAIRE

    Callendret, Benoît

    2002-01-01

    Le Virus Respiratoire Syncytial Bovin (VRSB) est une cause majeure de maladie respiratoire des jeunes bovins. La persistance du VRSB et du VRS humain à pu être démontrée in vitro sur différentes lignées cellulaires et in vivo sur des cobayes ou sur des sujets immunodéprimés. En revanche, la persistance du VRS in vivo chez son hôte naturel immunocompétent n'a jamais pu être mise en évidence. Elle a pourtant depuis longtemps été fortement suspectée à partir des données épidémiologiques. En outr...

  18. Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    D Tien Nguyen

    Full Text Available Human respiratory syncytial virus (HRSV and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These

  19. Engineering and expression of a RhoA peptide against respiratory syncytial virus infection in plants.

    Science.gov (United States)

    Ortega-Berlanga, Benita; Musiychuk, Konstantin; Shoji, Yoko; Chichester, Jessica A; Yusibov, Vidadi; Patiño-Rodríguez, Omar; Noyola, Daniel E; Alpuche-Solís, Ángel G

    2016-02-01

    MAIN CONCLUSION : A RhoA-derived peptide fused to carrier molecules from plants showed enhanced biological activity of in vitro assays against respiratory syncytial virus compared to the RhoA peptide alone or the synthetic RhoA peptide. A RhoA-derived peptide has been reported for over a decade as a potential inhibitor of respiratory syncytial virus (RSV) infection both in vitro and in vivo and is anticipated to be a promising alternative to monoclonal antibody-based therapy against RSV infection. However, there are several challenges to furthering development of this antiviral peptide, including improvement in the peptide’s bioavailability, development of an efficient delivery system and identification of a cost-effective production platform. In this study, we have engineered a RhoA peptide as a genetic fusion to two carrier molecules, either lichenase (LicKM) or the coat protein (CP) of Alfalfa mosaic virus. These constructs were introduced into Nicotiana benthamiana plants using a tobacco mosaic virus-based expression vector and targets purified. The results demonstrated that the RhoA peptide fusion proteins were efficiently expressed in N. benthamiana plants, and that two of the resulting fusion proteins, RhoA-LicKM and RhoA2-FL-d25CP, inhibited RSV growth in vitro by 50 and 80 %, respectively. These data indicate the feasibility of transient expression of this biologically active antiviral RhoA peptide in plants and the advantage of using a carrier molecule to enhance target expression and efficacy.

  20. The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways.

    Science.gov (United States)

    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

    2012-05-01

    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.

  1. Human metapneumovirus and respiratory syncytial virus detection in young children with acute bronchiolitis.

    Science.gov (United States)

    Teeratakulpisarn, Jamaree; Ekalaksananan, Tipaya; Pientong, Chamsai; Limwattananon, Chulaporn

    2007-01-01

    This study was conducted to detect human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in young children hospitalized with acute bronchiolitis, using reverse transcriptase polymerase chain reaction (RT-PCR). Nasopharyngeal secretions were collected from 170 children between 1 and 24 months of age admitted to two tertiary hospitals in northeastern Thailand, between 2002 and 2004. Acute bronchiolitis was defined as the first episode of wheezing associated with tachypnea, increased respiratory effort and an upper respiratory tract infection. Two-thirds (115/170) were positive for viral etiologies: 64.7% RSV (110/170) and 3.5% hMPV (6/170). One patient had a dual infection. hMPV was detected between August and November, while RSV was prevalent from July through March. The clinical manifestations among the 6 hMPV, RSV and non-RSV-infected children were similar. RSV was the leading cause of acute bronchiolitis in young children and hMPV had a low prevalence in northeastern Thailand.

  2. Clinical characterization of influenza A and human respiratory syncytial virus among patients with influenza like illness.

    Science.gov (United States)

    Saxena, Swati; Singh, Dharamveer; Zia, Amreen; Umrao, Jyoti; Srivastava, Naveen; Pandey, Ankita; Singh, Sushma; Bhattacharya, Piyali; Kumari, Reema; Kushwaha, Ramawadh; Dhole, T N

    2017-01-01

    Influenza A and Respiratory Syncytial Virus (RSV) has been recognized as a major cause of acute respiratory tract infection. H1N1 is one of the subtypes of influenza A, pandemic worldwide in July 2009, causing 18,449 deaths globally. To investigate the prevalence and clinical manifestation of the influenza A, H1N1pdm09, and RSV. Throat/nasal swab collected from the patients of all age group either outpatients/inpatients having respiratory illness from 2 to 5 days. The clinical data were recorded in a predesigned questionnaire. RNA was extracted and analyzed by real time PCR at a tertiary care center, 2009-2014. Total 4,352 samples tested for influenza A and H1N1. Out of 4,352, 32.2% (median positivity 21%; range 16-41% during 6 years) were positive for influenza A and 19% were H1N1 (median positivity 16.7%; range 8.7-23% during 6 years). Total 1653 samples were analyzed for RSV from 2011 to 2014, 12% were RSV positive (median positivity 11.35%; range 10-16.3% during 4 years). Pharyngitis, dyspnea were frequent symptoms in influenza A and H1N1 (P bronchiolitis and pneumonia were commonly present in RSV (P helpful for early and accurate diagnosis. J. Med. Virol. 89:49-54, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  4. Shift in the timing of respiratory syncytial virus circulation in a subtropical megalopolis: implications for immunoprophylaxis.

    Science.gov (United States)

    Paiva, Terezinha M; Ishida, Maria A; Benega, Margarete A; Constantino, Clóvis R A; Silva, Daniela B B; Santos, Kátia C O; Oliveira, Maria I; Barbosa, Helena A; Carvalhanas, Telma R M P; Schuck-Paim, Cynthia; Alonso, Wladimir J

    2012-11-01

    Respiratory syncytial virus (RSV) is the most common cause of severe respiratory infections worldwide, and an important cause of childhood bronchiolitis, pneumonia, and mortality. Although prevention of RSV infection by immunoprophylaxis with palivizumab has proved effective, a precise understanding of the timing of RSV outbreaks is necessary to ensure that infants are protected when RSV is circulating. In this study a consistent shift in the seasonal patterns of RSV circulation in southeast Brazil (São Paulo) is reported based on the analysis of 15 years of viral surveillance. Surveillance was conducted from 1996 to 2010 and involved the collection of samples from children with symptoms of acute respiratory infection. Putative changes in school terms, in the proportion of RSV genotypes infecting children and in the seasonal dynamics of several climatic parameters during the period were also investigated. The results revealed a progression in the timing of RSV seasons, with a shift in the onset and peak of RSV epidemics from 2007 onwards. Although lower rainfall and temperatures were associated with the onset of outbreaks, there was no evidence of changes in climate, school terms or in the relative proportion of genotypes in the period analyzed. These findings have direct implications for improving the prophylactic use of palivizumab, and stress the importance of fine tuning prophylaxis with recent surveillance data. In the case of São Paulo, palivizumab prophylaxis should be initiated earlier than suggested currently. Similar adjustments may be necessary in other regions. Copyright © 2012 Wiley Periodicals, Inc.

  5. Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques.

    Science.gov (United States)

    Grandin, Clément; Lucas-Hourani, Marianne; Clavel, Marine; Taborik, Fabrice; Vabret, Astrid; Tangy, Frédéric; Contamin, Hugues; Vidalain, Pierre-Olivier

    2015-04-01

    There is no large-scale therapy available against human respiratory syncytial virus (hRSV), a major pathogen responsible for acute respiratory diseases. Macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. However, the parameters that influence hRSV growth and control in this model are still poorly understood. We have documented in the following study the influence of age as well as repeated infections on the virological, clinical and immunological parameters of this animal model. Following intranasal inoculation, hRSV replicated in the upper respiratory tract for less than 15 days with no clinical signs regardless of age. Interestingly, we observed the induction of a local immune response at the nasal mucosa as assessed by expression profiles of inflammatory and IFN-stimulated genes. Animals also developed specific antibodies and were immune to reinfection. Thus, we showed that even in infant macaques, intranasal hRSV infection induced both local and systemic immune responses to efficiently control the virus. © 2015 The Authors.

  6. Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection.

    Science.gov (United States)

    Chiba, Eriko; Tomosada, Yohsuke; Vizoso-Pinto, Maria Guadalupe; Salva, Susana; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-10-01

    Previously we showed that orally administered Lactobacillus rhamnosus CRL1505 beneficially regulated the balance between pro- and anti-inflammatory mediators in the lungs of poly(I:C)-challenged mice, allowing an effective inflammatory response against the TLR3/RIG-I agonist but at the same time reducing tissue damage. The aim of the present study was to investigate whether oral administration of the CRL1505 strain was able to improve resistance against respiratory syncytial virus (RSV) infection in infant mice and to evaluate the immunological mechanisms involved in the immunobiotic effect. We demonstrated that treatment of 3-week old BALB/c mice with L. rhamnosus CRL1505 significantly reduce lung viral loads and tissue injuries after the challenge with RSV. Moreover, we showed that the protective effect achieved by the CRL1505 strain is related to its capacity to differentially modulate respiratory antiviral immune response. Our results shows that IFN-γ and IL-10 secreted in response to L. rhamnosus CRL1505 oral stimulation would modulate the pulmonary innate immune microenvironment conducting to the activation of CD103(+) and CD11b(high) dendritic cells and the generation of CD3(+)CD4(+)IFN-γ(+) Th1 cells with the consequent attenuation of the strong and damaging Th2 reactions associated with RSV challenge. Our results indicate that modulation of the common mucosal immune system by immunobiotics could favor protective immunity against respiratory viral pathogens with a high attack rate in early infancy, such as RSV. © 2013.

  7. Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors.

    Science.gov (United States)

    Grandin, Clément; Hourani, Marianne-Lucas; Janin, Yves L; Dauzonne, Daniel; Munier-Lehmann, Hélène; Paturet, Adeline; Taborik, Fabrice; Vabret, Astrid; Contamin, Hugues; Tangy, Frédéric; Vidalain, Pierre-Olivier

    2016-01-01

    There is imperious need for efficient therapies against ubiquitous and life-threatening respiratory viruses, foremost among them being the human respiratory syncytial virus (hRSV). Several research groups who performed functional screens for broad-spectrum antivirals identified compounds targeting the de novo pyrimidine biosynthesis pathway. Despite their strong antiviral activity in vitro, whether such antimetabolites are effective in vivo remains highly controversial. Here, we evaluated two potent pyrimidine biosynthesis inhibitors developed in our laboratory, IPPA17-A04 and GAC50, in a model of mild hRSV-infection in cynomolgus macaques. In this model, hRSV replication is restricted to the epithelium of the upper respiratory tract, and is compatible with a topical treatment by intranasal sprays. The local administration of palivizumab, a neutralizing anti-hRSV antibody used in clinics, significantly reduced virus replication. In contrast, pyrimidine biosynthesis inhibitors did not show any inhibitory effect on hRSV growth when delivered topically as experimented in our model. Our results should help to better define the potential applications of this class of antimetabolites in the treatment of viral infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Respiratory syncytial virus prophylaxis in Down syndrome: a prospective cohort study.

    Science.gov (United States)

    Yi, Hao; Lanctôt, Krista L; Bont, Louis; Bloemers, Beatrijs L P; Weijerman, Michel; Broers, Chantal; Li, Abby; Kiss, Alexander; Mitchell, Ian; Paes, Bosco

    2014-06-01

    Children with Down syndrome (DS) are at significant risk for respiratory syncytial virus (RSV) infection and related hospitalization. We compared hospitalization rates due to respiratory tract infection in children with DS aged Evaluation Study of Palivizumab registry between 2005 and 2012. The untreated group included 233 children with DS derived from a nationwide Dutch birth cohort from 2003 to 2005. Events during the RSV seasons were counted. Poisson regression analysis was performed to compare incidence rate ratios (95% confidence intervals [CIs]) between groups while controlling for observation length and known risk factors for severe RSV infection. In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects than in palivizumab recipients (incidence rate ratio 3.63; 95% CI, 1.52-8.67). The adjusted risk of hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11; 95% CI, 0.80-1.55). These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in children with DS during the first 2 years of life. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population. Copyright © 2014 by the American Academy of Pediatrics.

  9. Right and left ventricular function in hospitalized children with respiratory syncytial virus infection.

    Science.gov (United States)

    Horter, Thorsten; Nakstad, Britt; Ashtari, Omid; Solevåg, Anne Lee

    2017-01-01

    Extrapulmonary manifestations including cardiac dysfunction have been demonstrated in children with respiratory syncytial virus (RSV) infection requiring intensive care. The aim of this study was to examine cardiac function in hospitalized children with moderate RSV infection admitted to a regular pediatric ward. We used echocardiography to determine cardiac output, and right and left ventricular function in 26 patients (aged 2 weeks to 24 months) with RSV infection. The echocardiographic results were compared with s-troponin, the need for supplementary oxygen or noninvasive respiratory support, and capillary refill time. The number of measured s-troponins (ten [38%] of the included children) was too low to assess differences between children with elevated levels and those with normal levels. There were no differences in cardiac function between patients receiving oxygen treatment or respiratory support and those who did not. Capillary refill time did not correlate with any of the echocardiographic parameters. Both left and right ventricular output (mL/kg/min) was higher than published reference values. All other echocardiographic parameters were within the reference range. Children with moderate RSV infection had an increased left and right ventricular output, and cardiac function was well maintained. We conclude that routine cardiac ultrasound is not warranted in children with moderate RSV infection. The role of an elevated s-troponin in these patients remains to be determined.

  10. Safety, bioavailability and mechanism of action of nitric oxide to control Bovine Respiratory Disease Complex in calves entering a feedlot.

    Science.gov (United States)

    Regev-Shoshani, G; Vimalanathan, S; Prema, D; Church, J S; Reudink, M W; Nation, N; Miller, C C

    2014-04-01

    Bovine Respiratory Disease Complex (BRDc), a multi-factorial disease, negatively impacts the cattle industry. Nitric oxide (NO), a naturally occurring molecule, may have utility controlling incidence of BRDc. Safety, bioavailability, toxicology and tolerance/stress of administering NO to cattle is evaluated herein. Thirteen, crossbred, multiple-sourced, commingled commercial weaned beef calves were treated multiple times intranasally over a 4 week period with either a nitric oxide releasing solution (treatment) or saline (control). Exhaled NO, methemoglobin percent (MetHg) and serum nitrites demonstrated biological availability as a result of treatment. Cortisol levels, tissue nitrites, behavior and gross and macroscopic pathology of organs were all normal. Moreover, preliminary in vitro studies using Mannheimia haemolytica, Infectious Bovine Rhinotracheitis, Bovine Parainfluenza-3 and Bovine Respiratory Syncytial Virus, suggest a potential explanation for the previously demonstrated efficacy for BRDc. These data confirm the bioavailability, safety and lack of residual of NO treatment to cattle, along with the bactericidal and virucidal effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. First versus second year respiratory syncytial virus prophylaxis in chronic lung disease (2005-2015).

    Science.gov (United States)

    Wang, Daniel Y; Li, Abby; Paes, Bosco; Mitchell, Ian; Lanctôt, Krista L

    2017-03-01

    Children aged disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29 weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all p disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections. • The American Academy of Pediatrics [ 2 ] and the Canadian Paediatric Society [ 30 ] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS). • CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity.

  12. Seroprevalence of viral and bacterial diseases among the bovines in Himachal Pradesh, India

    OpenAIRE

    Shailja Katoch; Shweta Dohru; Mandeep Sharma; Vikram Vashist; Rajesh Chahota; Prasenjit Dhar; Aneesh Thakur; Subhash Verma

    2017-01-01

    Aim: The study was designed to measure the seroprevalence of viral and bacterial diseases: Infectious bovine rhinotracheitis, bovine viral diarrhea, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, brucellosis, and paratuberculosis among bovine of Himachal Pradesh during the year 2013-2015. Materials and Methods: The serum samples were collected from seven districts of state, namely, Bilaspur, Kangra, Kinnaur, Lahul and Spiti, Mandi, Sirmour, and Solan. The sam...

  13. Prevalence and clinical characteristics of human respiratory syncytial virus in Chinese adults with acute respiratory tract infection.

    Science.gov (United States)

    Xiang, Zichun; Gonzalez, Richard; Ren, Lili; Xiao, Yan; Chen, Lan; Zhang, Jing; Wang, Wei; Yang, Qingqing; Li, Jianguo; Zhou, Hongli; Vernet, Guy; Paranhos-Baccalà, Gláucia; Wang, Zhong; Wang, Jianwei

    2013-02-01

    Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illnesses worldwide. Although the prevalence and clinical manifestations of the two subtypes, RSV-A and RSV-B, have been studied in some detail in infants and young children, they have not been determined in adults. To evaluate the prevalence of the RSV subtypes and disease severity between RSV-A and RSV-B infections in adults, nasal and throat swabs that were collected from patients ≥15 years old who sought medical care for acute respiratory infections at the Fever Clinic of the Peking Union Medical College Hospital in Beijing, China between May 2005 and April 2010. The samples were tested for RSV infection using PCR and sequencing analysis. RSV was detected in 95 (1%) of the adult patients, of whom 53 (55.8%) were positive for RSV-A and 42 (44.2%) for RSV-B. The incidence of RSV infections increased with age (χ(2) = 37.17, P = 1.66E-07). Demographic data and clinical manifestations of RSV-A were similar to those of RSV-B. Although RSV-A and RSV-B co-circulated during the 2005-2006 and 2008-2009 seasons, RSV-A was predominant in the 2006-2008 seasons, whereas RSV-B was predominant in the 2009-2010 season. Upper respiratory tract infections were diagnosed in most RSV-infected patients (n = 80, 84.2%), and three patients suffered from pulmonary infection. This is the first study to provide data on the prevalence and clinical manifestations of RSV subgroups among Chinese adults with fever and acute illness, over five successive epidemic seasons. Copyright © 2012 Wiley Periodicals, Inc.

  14. Respiratory syncytial virus subtype ON1/NA1/BA9 predominates in hospitalized children with lower respiratory tract infections.

    Science.gov (United States)

    Fan, Ruyan; Fan, Chuping; Zhang, Jian; Wen, Bo; Lei, Yefei; Liu, Chan; Chen, Lijuan; Liu, Wenpei; Wang, Chuan; Qu, Xiaowang

    2017-02-01

    Respiratory syncytial virus (RSV) infection is the leading cause of acute respiratory tract disease in children less than 5 years old. The aim of this study was to further elucidate the molecular properties and clinical characteristics of RSV infection. The study sample included 238 patients respiratory tract infection (URTI or LRTI) in the Pediatric Department at the First People's Hospital of Chenzhou, South China in 2014. We subjected nasopharyngeal aspirate (NPA) or nasal swab (NS) samples from the patients to indirect fluorescence assay screens. RSV G genes were amplified by reverse transcription-PCR (RT-PCR) and sequenced. Of the 238 patients screened, 64 (26.8%) were confirmed to have RSV infections. Of those 64 confirmed RSV infection cases, 39 (60.9%) had subtype BA9, 13 (20.3%) had the recently identified subtype ON1, 11 (17.2%) had subtype NA1, and 1 (1.6%) had subtype GB2. The predominant presentation was LRTI with coughing, sputum production, fever, and wheezing. RSV subtype NA1 and BA9 infections were found mostly in infants, whereas the age distribution of subtype ON1 infections was more uniform across the age bands. Phylogenetic analysis indicated that, compared with the prototype strain A2, all ON1 and most NA1 isolates had lost one potential N-glycosylation site at amino acid 251 and 249 due to T251K and N249Y substitution, respectively. These findings suggest that NA1, BA9, and ON1 are the dominant RSV subtypes causing respiratory tract infections in young children presenting to the hospital in South China. J. Med. Virol. 89:213-221, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-03-21

    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.

  17. Macronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children.

    Science.gov (United States)

    Ferolla, F Martín; Hijano, Diego R; Acosta, Patricio L; Rodríguez, Andrea; Dueñas, Karina; Sancilio, Andrea; Barboza, Edgar; Caría, Adriana; Gago, Guadalupe Fernández; Almeida, Rodrigo Egües; Castro, Laura; Pozzolo, Cecilia; Martínez, María V; Grimaldi, Luciano Alva; Rebec, Beatriz; Calvo, Mariel; Henrichsen, Julieta; Nocito, Celina; González, Mariela; Barbero, Guillermo; Losada, Juan Ves; Caballero, Mauricio T; Zurankovas, Valeria; Raggio, Mirta; Schavlovsky, Graciela; Kobylarz, Alicia; Wimmenauer, Vera; Bugna, Jimena; Williams, John V; Sastre, Gustavo; Flamenco, Edgardo; Pérez, Alberto Rodríguez; Ferrero, Fernando; Libster, Romina; Grijalva, Carlos G; Polack, Fernando P

    2013-05-01

    Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. We defined the burden of life-threatening (O(2) saturation [O(2) sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children's pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O(2) sat less than 93% on admission were included. Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5-2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV(+)), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4-1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15-9.44] to 7.36 [95% CI, 2.41-22.5] versus the lowest quartile). Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.

  18. Respiratory-syncytial-virus- and rhinovirus-related bronchiolitis in children aged hospital.

    Science.gov (United States)

    Paul, S P; Mukherjee, A; McAllister, T; Harvey, M J; Clayton, B A; Turner, P C

    2017-08-01

    Bronchiolitis is the most common reason for hospitalization in young children. In addition to respiratory syncytial virus (RSV), other viruses have been increasingly implicated. Guidance on testing has also changed. To compare clinicopathological outcomes in young children admitted with bronchiolitis due to RSV in comparison with rhinovirus (RV), and identify associated risk/epidemiological factors. Children aged less than two years admitted to hospital with a clinical diagnosis of bronchiolitis with positive results for either RSV or RV were included in this study. Polymerase-chain-reaction-negative cases using an extended respiratory virus panel served as a control group. Retrospective data were collected on sex, risk factors, respiratory support, intravenous fluids and antibiotics. Outcomes such as length of stay (LOS) and need for transfer to the high-dependency unit/paediatric intensive care unit were included. Two hundred and twenty-seven out of 437 nasopharyngeal aspirate samples were positive for either RSV (N = 162) or RV (N = 65). The median age of cases was three months and 75% had at least one risk factor. Risk factors were higher in the RV group (P = 0.004). RV accounted for the majority of cases outside the RSV season (P < 0.01). RV-associated bronchiolitis had a longer LOS (more than seven days) (P < 0.05) and increased need for chest X-rays and/or antibiotics (P < 0.05). Use of intravenous fluids and respiratory support were higher in the RV group, but the difference was not significant. RV is the second most common pathogen associated with bronchiolitis and is isolated all year round. This may be important in those with risk factors resulting in prolonged LOS. Further research is necessary to establish the exact role of RV in this common condition, particularly outside the traditional RSV season. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  19. Molecular and clinical characterization of human respiratory syncytial virus in South Korea between 2009 and 2014.

    Science.gov (United States)

    Park, E; Park, P H; Huh, J W; Yun, H J; Lee, H K; Yoon, M H; Lee, S; Ko, G

    2017-11-01

    Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT-PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6-5·1) and wheezing (OR = 2·8, 95% CI 1·7-4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8-46·7), while the NA1 genotype was associated with the pediatric patients' gender (males, OR = 2·4, 95% CI 1·1-5·4) and presence of chills (OR = 5·1, 95% CI 1·1-27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2-20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.

  20. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection.

    Science.gov (United States)

    Tomosada, Yohsuke; Chiba, Eriko; Zelaya, Hortensia; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-08-15

    Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible

  1. Vitamin D Levels Are Unrelated to the Severity of Respiratory Syncytial Virus Bronchiolitis Among Hospitalized Infants.

    Science.gov (United States)

    Beigelman, Avraham; Castro, Mario; Schweiger, Toni L; Wilson, Brad S; Zheng, Jie; Yin-DeClue, Huiquing; Sajol, Geneline; Giri, Tusar; Sierra, Oscar L; Isaacson-Schmid, Megan; Sumino, Kaharu; Schechtman, Kenneth B; Bacharier, Leonard B

    2015-09-01

    Vitamin D deficiency at birth has been reported as a risk factor for respiratory syncytial virus (RSV) lower respiratory tract infection during the first year of life. Limited data are available on whether an infant's vitamin D status is associated with the severity of acute RSV bronchiolitis. Infants first episode of RSV bronchiolitis were enrolled into the RSV Bronchiolitis in Early Life II cohort. We investigated the relationships between vitamin D status at enrollment and the following indicators of bronchiolitis severity: duration of hospitalization, lowest oxygen saturation measured during hospitalization, and bronchiolitis severity score. Among the 145 enrolled infants, the median (quartile 1 [Q1], Q3) serum 25-OH-VitD level was 36.8 (29.8, 42.3) ng/mL, with 14 infants (9.7%) having deficient serum vitamin D levels (25-OH-VitD bronchiolitis severity did not differ between infants who were vitamin D-deficient and nondeficient: duration of hospitalization (P = .53), lowest oxygen saturation (P = .45), and bronchiolitis severity score (P = .97), even after adjusting for age, and for infant's formula consumption. Among this cohort of infants that were hospitalized for RSV bronchiolitis, vitamin D status at the time of bronchiolitis was not associated with indicators of acute bronchiolitis severity.

  2. [Study of a respiratory syncytial virus diagnostic test kit based on immunochromatography].

    Science.gov (United States)

    Saikusa, Miwako; Takeuchi, Yoshinao; Chou, Hideo; Abe, Takashi; Munemura, Tetsuya; Kawakami, Chiharu

    2003-06-01

    We carried out clinical and basic studies of the Directigen Lateral Flow RSV (Becton, Dickinson and Company, USA), a rapid test kit that detects respiratory syncytial virus (hereinafter referred to as "RSV") antigens based on immunochromatography. For the clinical study, 103 nasopharyngeal aspirates from patients with acute respiratory infections were used to evaluate the kit. Compared to the cell culture method, the Directigen Lateral Flow RSV showed a sensitivity of 100% (16/16) and a specificity of 94.3% (82/87), and an agreement rate of 95.1% (98/103). When compared to conventional testing kits, we found that the total agreement rate with the Directigen RS (Nippon Becton Dickinson and Company) was 88.3% (91/103) and with RSV TestPack (Dainabot Co., Ltd.) was 91.3% (94/103). The detection limit of the Directigen Lateral Flow RSV was 2 x 10(3) PFU/ml for both RSV subgroups A and B. In the crossreactivity test, only RSV was found positive. No other microorganisms were crossreactive. We also studied storage stability of nasopharyngeal aspirates and found that stability was not affected by storage at room and refrigerator temperatures for 14 days. Taken all together, the Directigen Lateral Flow RSV is useful for the diagnosis of RSV infection in a clinical setting because its performance is equivalent to conventional testing kits and is easy to use.

  3. RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function.

    Science.gov (United States)

    Tian, Jane; Huang, Kelly; Krishnan, Subramaniam; Svabek, Catherine; Rowe, Daniel C; Brewah, Yambasu; Sanjuan, Miguel; Patera, Andriani C; Kolbeck, Roland; Herbst, Ronald; Sims, Gary P

    2013-08-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.

  4. Hsp90 inhibitors exhibit resistance-free antiviral activity against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Ron Geller

    Full Text Available Respiratory syncytial virus (RSV is a major cause of respiratory illness in young children, leading to significant morbidity and mortality worldwide. Despite its medical importance, no vaccine or effective therapeutic interventions are currently available. Therefore, there is a pressing need to identify novel antiviral drugs to combat RSV infections. Hsp90, a cellular protein-folding factor, has been shown to play an important role in the replication of numerous viruses. We here demonstrate that RSV requires Hsp90 for replication. Mechanistic studies reveal that inhibition of Hsp90 during RSV infection leads to the degradation of a viral protein similar in size to the RSV L protein, the viral RNA-dependent RNA polymerase, implicating it as an Hsp90 client protein. Accordingly, Hsp90 inhibitors exhibit antiviral activity against laboratory and clinical isolates of RSV in both immortalized as well as primary differentiated airway epithelial cells. Interestingly, we find a high barrier to the emergence of drug resistance to Hsp90 inhibitors, as extensive growth of RSV under conditions of Hsp90 inhibition did not yield mutants with reduced sensitivity to these drugs. Our results suggest that Hsp90 inhibitors may present attractive antiviral therapeutics for treatment of RSV infections and highlight the potential of chaperone inhibitors as antivirals exhibiting high barriers to development of drug resistance.

  5. Allergy skin test responses during experimental infection with respiratory syncytial virus.

    Science.gov (United States)

    Skoner, David P; Gentile, Deborah A; Angelini, Betty; Doyle, William J

    2006-06-01

    Allergy skin testing is one of the most frequently performed physician office procedures. Many factors can affect the results of those tests, including the well-defined suppressive effect of systemic antihistamines. False-positive allergen skin test results are known to occur; however, contributing factors are not well understood. To determine whether a viral upper respiratory tract infection affects allergy skin test responsiveness. We performed skin tests with histamine and a panel of geographically relevant inhalant allergens on 16 adults before and 3, 6, and 21 days after experimental exposure to respiratory syncytial virus (RSV), a virus that causes signs and symptoms of a cold. The RSV exposure, with and without documented infection, caused increased wheal and flare areas to histamine and allergen and de novo positive allergen test responses in individuals with no measurable responses at baseline. These were noted as late as 21 days after RSV exposure and may be consistent with mediation by up-regulated neurogenic inflammation during RSV infection. These results may have implications for explaining the cause of such well-known complications of RSV infection as otitis media, bronchiolitis, and asthmatic exacerbation.

  6. NK cell immunophenotypic and genotypic analysis of infants with severe respiratory syncytial virus infection.

    Science.gov (United States)

    Noyola, Daniel E; Juárez-Vega, Guillermo; Monjarás-Ávila, César; Escalante-Padrón, Francisco; Rangel-Ramírez, Verónica; Cadena-Mota, Sandra; Monsiváis-Urenda, Adriana; García-Sepúlveda, Christian A; González-Amaro, Roberto

    2015-07-01

    Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants. Reduced numbers of NK cells have been reported in infants with severe RSV infection; however, the precise role of NK cells during acute RSV infection is unclear. In this study the NK and T cell phenotypes, LILRB1 gene polymorphisms and KIR genotypes of infants hospitalized with RSV infection were analyzed. Compared to controls, infants with acute RSV infection showed a higher proportion of LILRB1+ T cells; in addition, a subgroup of infants with RSV infection showed an increase in LILRB1+ NK cells. No differences in NKG2C, NKG2A, or CD161 expression between RSV infected infants and controls were observed. LILRB1 genotype distribution of the rs3760860 A>G, and rs3760861 A>G single nucleotide polymorphisms differed between infants with RSV infection and healthy donors, whereas no differences in any of the KIR genes were observed. Our results suggest that LILRB1 participates in the pathogenesis of RSV infection. Further studies are needed to define the role of LILRB1+ NK in response to RSV and to confirm an association between LILRB1 polymorphisms and the risk of severe RSV infection. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  7. Comparative epidemiology of human metapneumovirus- and respiratory syncytial virus-associated hospitalizations in Guatemala

    Science.gov (United States)

    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 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

  8. A Cross-Study Biomarker Signature of Human Bronchial Epithelial Cells Infected with Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo Gardinassi

    2016-01-01

    Full Text Available Respiratory syncytial virus (RSV is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. Despite of advances in diagnosis and treatment, biomarkers of RSV infection are still unclear. To understand the host response and propose signatures of RSV infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line—BEAS-2B—infected with different strains of this virus. However, the evolution of statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections. In view of those facts publicly available microarray datasets from RSV-infected BEAS-2B cells were analyzed with linear model-based statistics and the platform for functional analysis InnateDB. The results from those analyses argue for the reevaluation of previously reported transcription patterns and biological pathways in BEAS-2B cell lines infected with RSV. Importantly, this study revealed a biosignature constituted by genes such as ABCC4, ARMC8, BCLAF1, EZH1, FAM118A, FAM208B, FUS, HSPH1, KAZN, MAP3K2, N6AMT1, PRMT2, S100PBP, SERPINA1, TLK2, ZNF322, and ZNF337 which should be considered in the development of new molecular diagnosis tools.

  9. Molecular characterization of human respiratory syncytial virus detected from central India.

    Science.gov (United States)

    Sahu, Mahima; Shukla, Mohan K; Barde, Pradip V

    2017-10-01

    Human Respiratory syncytial virus (hRSV) is the major cause of respiratory tract infection in both children and adults, virtually all children acquire infection with hRSV by the age of 3 years. Two subgroups of the virus, hRSV-A and hRSV-B based on sequence variability of G protein gene are divided into 11 and 17 genotypes, respectively. Very limited data regarding circulating genotypes is available from India. This study aimed to detect and characterize the circulating genotype of hRSV from central India. Throat swabs collected from patient's having influenza like illness (ILI) were subjected to RT-PCR for diagnosis, further sequencing and phylogenetic analysis was performed using primers specific for C-terminal end of G gene. Out of 526 tested samples 62 (12%) were found positive, 90% cases were from children under 3-year age children. Both hRSV-A and hRSV-B were detected in equal proportions. Sequence analysis of 15 samples revealed circulation of genotypes NA1, ON1 of hRSV-A, and BA9 of hRSV-B. We advocate molecular surveillance of hRSV for better patient management and epidemiological monitoring. © 2017 Wiley Periodicals, Inc.

  10. Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Eugen-Olsen, Jesper; Koch, A

    2006-01-01

    BACKGROUND: As respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause serious respiratory tract infections, the routes of transmission of these viruses are important to elucidate. We examined the modes of virus shedding and shedding duration of RSV and hMPV in young children...... of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members....... METHODS: From each child in a group of 44 children (37 RSV-positive, 6 hMPV-positive, and 1 co-infected child), aged between 0.5-38 months, hospitalised at Hvidovre Hospital, Copenhagen, Denmark, one nasopharyngeal aspirate (NPA), saliva, urine, and faeces sample were collected at inclusion and weekly...

  11. A Short Double-Stapled Peptide Inhibits Respiratory Syncytial Virus Entry and Spreading.

    Science.gov (United States)

    Gaillard, Vanessa; Galloux, Marie; Garcin, Dominique; Eléouët, Jean-François; Le Goffic, Ronan; Larcher, Thibaut; Rameix-Welti, Marie-Anne; Boukadiri, Abdelhak; Héritier, Julien; Segura, Jean-Manuel; Baechler, Elodie; Arrell, Miriam; Mottet-Osman, Geneviève; Nyanguile, Origène

    2017-04-01

    Synthetic peptides derived from the heptad repeat (HR) of fusion (F) proteins can be used as dominant negative inhibitors to inhibit the fusion mechanism of class I viral F proteins. Here, we have performed a stapled-peptide scan across the HR2 domain of the respiratory syncytial virus (RSV) F protein with the aim to identify a minimal domain capable of disrupting the formation of the postfusion six-helix bundle required for viral cell entry. Constraining the peptides with a single staple was not sufficient to inhibit RSV infection. However, the insertion of double staples led to the identification of novel short stapled peptides that display nanomolar potency in HEp-2 cells and are exceptionally robust to proteolytic degradation. By replacing each amino acid of the peptides by an alanine, we found that the substitution of residues 506 to 509, located in a patch of polar contacts between HR2 and HR1, severely affected inhibition. Finally, we show that intranasal delivery of the most potent peptide to BALB/c mice significantly decreased RSV infection in upper and lower respiratory tracts. The discovery of this minimal HR2 sequence as a means for inhibition of RSV infection provides the basis for further medicinal chemistry efforts toward developing RSV fusion antivirals. Copyright © 2017 Gaillard et al.

  12. Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

    Science.gov (United States)

    Espinoza, Janyra A; León, Miguel A; Céspedes, Pablo F; Gómez, Roberto S; Canedo-Marroquín, Gisela; Riquelme, Sebastían A; Salazar-Echegarai, Francisco J; Blancou, Phillipe; Simon, Thomas; Anegon, Ignacio; Lay, Margarita K; González, Pablo A; Riedel, Claudia A; Bueno, Susan M; Kalergis, Alexis M

    2017-07-01

    Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection. Copyright © 2017 by The American Association of Immunologists, Inc.

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

    Science.gov (United States)

    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.

  14. Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Coyle Peter V

    2011-01-01

    Full Text Available Abstract Background Human respiratory syncytial virus (RSV causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs. Methods To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers. Results RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates. Conclusions The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

  15. Latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (RSV): a global comparative review.

    Science.gov (United States)

    Bloom-Feshbach, Kimberly; Alonso, Wladimir J; Charu, Vivek; Tamerius, James; Simonsen, Lone; Miller, Mark A; Viboud, Cécile

    2013-01-01

    There is limited information on influenza and respiratory syncytial virus (RSV) seasonal patterns in tropical areas, although there is renewed interest in understanding the seasonal drivers of respiratory viruses. We review geographic variations in seasonality of laboratory-confirmed influenza and RSV epidemics in 137 global locations based on literature review and electronic sources. We assessed peak timing and epidemic duration and explored their association with geography and study settings. We fitted time series model to weekly national data available from the WHO influenza surveillance system (FluNet) to further characterize seasonal parameters. Influenza and RSV activity consistently peaked during winter months in temperate locales, while there was greater diversity in the tropics. Several temperate locations experienced semi-annual influenza activity with peaks occurring in winter and summer. Semi-annual activity was relatively common in tropical areas of Southeast Asia for both viruses. Biennial cycles of RSV activity were identified in Northern Europe. Both viruses exhibited weak latitudinal gradients in the timing of epidemics by hemisphere, with peak timing occurring later in the calendar year with increasing latitude (Pvirus activity in individual years. Information on seasonal patterns remains limited in large undersampled regions, included Africa and Central America. Future studies should attempt to link the observed latitudinal gradients in seasonality of viral epidemics with climatic and population factors, and explore regional differences in disease transmission dynamics and attack rates.

  16. Respiratory syncytial virus is present in the neonatal intensive care unit.

    Science.gov (United States)

    Homaira, Nusrat; Sheils, Joanne; Stelzer-Braid, Sacha; Lui, Kei; Oie, Ju-Lee; Snelling, Tom; Jaffe, Adam; Rawlinson, William

    2016-02-01

    Nosocomial transmission of respiratory syncytial virus (RSV) occurs in children within the neonatal intensive care unit (NICU). During peak community RSV transmission, three swabs were collected from the nose, hand and personal clothing of visitors and health care workers (HCW) in NICU once every week for eight weeks. Nasal swabs were collected from every third neonate and from any neonate clinically suspected of having a respiratory infection. Environmental sampling of high touch areas was done once during the study period. All swabs were tested for RSV using real time RT-PCR. There were 173 (519 total) and 109 (327 total) swabs, each of nose, hand and dress from 84 HCWs and 80 visitors respectively and 81 nasal swabs from 55 neonates collected. Thirty five environmental swabs from surfaces of the beds, side tables, counter tops, chairs, tables and computers were collected. Overall 1% of nasal swabs from each of HCWs, visitors and neonates, 4% of dress specimens from visitors and 9% of environmental swabs were positive for RSV-RNA. The results suggest that though the risk for RSV in the NICU remains low, personnel clothing are contaminated with RSV-RNA and may have a role in transmission. © 2015 Wiley Periodicals, Inc.

  17. Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Emma Rey-Jurado

    2017-03-01

    Full Text Available The human respiratory syncytial virus (hRSV is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

  18. Activation Pathway of a Nucleoside Analog Inhibiting Respiratory Syncytial Virus Polymerase.

    Science.gov (United States)

    Jordan, Paul C; Stevens, Sarah K; Tam, Yuen; Pemberton, Ryan P; Chaudhuri, Shuvam; Stoycheva, Antitsa D; Dyatkina, Natalia; Wang, Guangyi; Symons, Julian A; Deval, Jerome; Beigelman, Leo

    2017-01-20

    Human respiratory syncytial virus (RSV) is a negative-sense RNA virus and a significant cause of respiratory infection in infants and the elderly. No effective vaccines or antiviral therapies are available for the treatment of RSV. ALS-8176 is a first-in-class nucleoside prodrug inhibitor of RSV replication currently under clinical evaluation. ALS-8112, the parent molecule of ALS-8176, undergoes intracellular phosphorylation, yielding the active 5'-triphosphate metabolite. The host kinases responsible for this conversion are not known. Therefore, elucidation of the ALS-8112 activation pathway is key to further understanding its conversion mechanism, particularly given its potent antiviral effects. Here, we have identified the activation pathway of ALS-8112 and show it is unlike other antiviral cytidine analogs. The first step, driven by deoxycytidine kinase (dCK), is highly efficient, while the second step limits the formation of the active 5'-triphosphate species. ALS-8112 is a 2'- and 4'-modified nucleoside analog, prompting us to investigate dCK recognition of other 2'- and 4'-modified nucleosides. Our biochemical approach along with computational modeling contributes to an enhanced structure-activity profile for dCK. These results highlight an exciting potential to optimize nucleoside analogs based on the second activation step and increased attention toward nucleoside diphosphate and triphosphate prodrugs in drug discovery.

  19. Watsonianone A from Rhodomyrtus tomentosa Fruit Attenuates Respiratory-Syncytial-Virus-Induced Inflammation In Vitro.

    Science.gov (United States)

    Zhuang, Ling; Chen, Li-Feng; Zhang, Yu-Bo; Liu, Zhong; Xiao, Xu-Hui; Tang, Wei; Wang, Guo-Cai; Song, Wen-Jun; Li, Yao-Lan; Li, Man-Mei

    2017-05-03

    Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 ± 1.6 μM. Enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor κB (NF-κB) activation by suppressing IκBα phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-κB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced inflammation via the suppression of ROS-sensitive inflammatory signaling.

  20. Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia-Implications for Vaccine Design.

    Science.gov (United States)

    Rey-Jurado, Emma; Kalergis, Alexis M

    2017-03-04

    The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

  1. A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus.

    Science.gov (United States)

    Do, Lien Anh Ha; van Doorn, H Rogier; Bryant, Juliet E; Nghiem, My Ngoc; Nguyen Van, Vinh Chau; Vo, Cong Khanh; Nguyen, Minh Dung; Tran, Tinh Hien; Farrar, Jeremy; de Jong, Menno D

    2012-01-01

    Improved diagnostic tools for rapid detection, quantitation, and subgrouping of human respiratory syncytial virus (RSV) are needed to aid the development and evaluation of novel intervention strategies. A quantitative real-time RT-PCR using specific locked nucleic acid (LNA) probes was developed to identify RSV and to distinguish RSV subgroups A and B (RSV LNA assay). RSV subgroup diversity and the relationship between viral load and disease severity in confirmed RSV infections were also explored. 264 archived respiratory specimens from pediatric patients were tested in parallel using the commercial multiplex Seeplex™ RV detection kit (Seegene) and the novel RSV LNA assay. The LNA assay demonstrated a significantly higher sensitivity than Seeplex, improving overall detection rates from 24% (64/264) to 32% (84/264). Detection limits of 9.0×10(1) and 6.0×10(2)copies/mL were observed for RSV A and B, respectively. RSV A was detected in 53/84 (63%) cases, and 31/84 (37%) were positive for RSV B. This novel method offers a rapid, quantitative, highly specific and sensitive approach to laboratory diagnosis of RSV. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    OpenAIRE

    Br?ggmann, D?rthe; K?ster, Corinna; Klingelh?fer, Doris; Bauer, Jan; Ohlendorf, Daniela; Bundschuh, Matthias; David A. Groneberg

    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 ...

  3. Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus▿

    OpenAIRE

    Kohlmann, Rebekka; Schwannecke, Sarah; Tippler, Bettina; Ternette, Nicola; Temchura, Vladimir V.; Tenbusch, Matthias; Überla, Klaus; Grunwald, Thomas

    2009-01-01

    Adenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codon-optimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the c...

  4. Novel Interventions for Bovine Respiratory Disease.

    Science.gov (United States)

    Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune and metabolic responses to a combined viral-bacterial respiratory disease challenge. Beef heifers (n = 32; 324 ± 19.2 kg BW) were selected and randomly assigned to one of two treatmen...

  5. Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.

    Science.gov (United States)

    Hause, Ben M; Collin, Emily A; Anderson, Joe; Hesse, Richard A; Anderson, Gary

    2015-01-01

    Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.

  6. Mammalian Cell-Derived Respiratory Syncytial Virus-Like Particles Protect the Lower as well as the Upper Respiratory Tract.

    Directory of Open Access Journals (Sweden)

    Pramila Walpita

    Full Text Available Globally, Respiratory Syncytial Virus (RSV is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in USA alone, between 85,000 and 144,000 infants are hospitalized every year. To date, there is no licensed vaccine. We have evaluated vaccine potential of mammalian cell-derived native RSV virus-like particles (RSV VLPs composed of the two surface glycoproteins G and F, and the matrix protein M. Results of in vitro testing showed that the VLPs were functionally assembled and immunoreactive, and that the recombinantly expressed F protein was cleaved intracellularly similarly to the virus-synthesized F protein to produce the F1 and F2 subunits; the presence of the F1 fragment is critical for vaccine development since all the neutralizing epitopes present in the F protein are embedded in this fragment. Additional in vitro testing in human macrophage cell line THP-1 showed that both virus and the VLPs were sensed by TLR-4 and induced a Th1-biased cytokine response. Cotton rats vaccinated with RSV VLPs adjuvanted with alum and monophosphoryl lipid A induced potent neutralizing antibody response, and conferred protection in the lower as well as the upper respiratory tract based on substantial virus clearance from these sites. To the best of our knowledge, this is the first VLP/virosome vaccine study reporting protection of the lower as well as the upper respiratory tract: Prevention from replication in the nose is an important consideration if the target population is infants < 6 months of age. This is because continued virus replication in the nose results in nasal congestion and babies at this age are obligate nose breathers. In conclusion, these results taken together suggest that our VLPs show promise to be a safe and effective vaccine for RSV.

  7. Mammalian Cell-Derived Respiratory Syncytial Virus-Like Particles Protect the Lower as well as the Upper Respiratory Tract

    Science.gov (United States)

    Walpita, Pramila; Johns, Lisa M.; Tandon, Ravi; Moore, Martin L.

    2015-01-01

    Globally, Respiratory Syncytial Virus (RSV) is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in USA alone, between 85,000 and 144,000 infants are hospitalized every year. To date, there is no licensed vaccine. We have evaluated vaccine potential of mammalian cell-derived native RSV virus-like particles (RSV VLPs) composed of the two surface glycoproteins G and F, and the matrix protein M. Results of in vitro testing showed that the VLPs were functionally assembled and immunoreactive, and that the recombinantly expressed F protein was cleaved intracellularly similarly to the virus-synthesized F protein to produce the F1 and F2 subunits; the presence of the F1 fragment is critical for vaccine development since all the neutralizing epitopes present in the F protein are embedded in this fragment. Additional in vitro testing in human macrophage cell line THP-1 showed that both virus and the VLPs were sensed by TLR-4 and induced a Th1-biased cytokine response. Cotton rats vaccinated with RSV VLPs adjuvanted with alum and monophosphoryl lipid A induced potent neutralizing antibody response, and conferred protection in the lower as well as the upper respiratory tract based on substantial virus clearance from these sites. To the best of our knowledge, this is the first VLP/virosome vaccine study reporting protection of the lower as well as the upper respiratory tract: Prevention from replication in the nose is an important consideration if the target population is infants virus replication in the nose results in nasal congestion and babies at this age are obligate nose breathers. In conclusion, these results taken together suggest that our VLPs show promise to be a safe and effective vaccine for RSV. PMID:26172453

  8. Prevailing genotype distribution and characteristics of human respiratory syncytial virus in northeastern China.

    Science.gov (United States)

    Zheng, Yuxuan; Liu, Li; Wang, Shaohua; Li, Zhaolong; Hou, Min; Li, Jingliang; Yu, Xiao-Fang; Zhang, Wenyan; Hua, Shucheng

    2017-02-01

    Although human respiratory syncytial virus (RSV) is one of the most common viruses inducing respiratory tract infections in young children and the elderly, the genotype distribution and characteristics of RSV in northeastern China have not been investigated. Here, we identified 25 RSV-A and 8 RSV-B strains from 80 samples of patients with respiratory infections between February 2015 and May 2015. All 25 RSV-A viruses were classified as the ON1 genotype, which rapidly spread and became the dominant genotype in the world since being identified in Ontario (Canada) in December 2010. All eight RSV-B viruses belonged to the BA genotype with a 60-nucleotide duplication, seven of which formed two new genotypes, BA-CCA and BA-CCB. The remaining RSV-B virus clustered with one of the Hangzhou strains belonging to genotype BA11. Construction of a phylogenetic tree and amino acid substitution analysis showed that Changchun ON1 viruses exclusively constituted Lineages 3, 5 and 6, and contained several unique and newly identified amino acid substitutions, including E224G, R244K, L289I, Y297H, and L298P. Selective pressure was also evaluated, and various N and O-glycosylation sites were predicted. This study provides the first genetic analysis of RSV in northeastern China and may facilitate a better understanding of the evolution of this virus locally and globally. J. Med. Virol. 89:222-233, 2017. © 2016 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

  9. Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.

    Science.gov (United States)

    Cade, A; Brownlee, K G; Conway, S P; Haigh, D; Short, A; Brown, J; Dassu, D; Mason, S A; Phillips, A; Eglin, R; Graham, M; Chetcuti, A; Chatrath, M; Hudson, N; Thomas, A; Chetcuti, P A

    2000-02-01

    To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. A multicentre randomised double blind placebo controlled trial. Infants admitted to hospital with their first episode of RSV positive bronchiolitis. Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

  10. THE EFFICACY OF THE COSTS ON SEVERE RESPIRATORY SYNCYTIAL INFECTION PREVENTION WITH PALIVIZUMAB IN PRETERM INFANTS

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2012-01-01

    Full Text Available Respiratory syncytial virus plays a significant role in etiology of respiratory infections in infants, and preterm children have muchhigher risk of severe course of the disease, than common population of children at the age less than 2 years old. Palivizumab is usedefficiently to prevent this infection. The aim of this study was to assess the efficacy of the costs on palivizumab in preterm childrenin the Russian Federation. The assessment was based on meta-analysis of randomized clinical trials. According to the World Health organization recommendations, the acceptable value of the variable «costs/efficacy» must not be higher than threefold of the gross domestic product per person. On the assumption of this fact, the coefficient «costs/efficacy» for the Russian Federation according to the 2011 year results must not be higher than 1140 thousand rubles per 1 extra year of life. Analysis from the position of health care system shows, that coefficient «costs/efficacy» with palivazumab usage in children with gestation age from 28 to 32 weeks rangesfrom 594,4 to 1030,4 thousand roubles per 1 extra year of life when starting the prophylaxis during first 6 month of life. Under the social perspective of the study (accounting for direct and indirect costs the coefficient «costs/efficacy» decreases to 515,8–951,8 thousands roubles per 1 extra year of life. Thereby, nowadays the prophylaxis of severe respiratory cyncytial infection with palivazumab is acceptable according to the economical point of view in preterm children with the gestation age 32 weeks and less when starting during first 6 months of life.

  11. Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America.

    Science.gov (United States)

    Bardach, Ariel; Rey-Ares, Lucila; Cafferata, María Luisa; Cormick, Gabriela; Romano, Marina; Ruvinsky, Silvina; Savy, Vilma

    2014-03-01

    Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0–51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2–24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28–54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2–2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9–16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America. © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.

  12. Respiratory syncytial virus infection outbreak among pediatric patients with oncologic diseases and/or BMT.

    Science.gov (United States)

    Anak, Sema; Atay, Didem; Unuvar, Aysegul; Garipardic, Mesut; Agaoglu, Leyla; Ozturk, Gulyuz; Karakas, Zeynep; Devecioglu, Omer

    2010-03-01

    Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous/allogeneic hematopoetic stem cell transplantation (HSCT). There have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Two RSV infection outbreaks developed between February-April 2006 and January-March 2009 in hospitalized pediatric patients for various hemato-oncological diseases + or - HSCT. A survey of respiratory viruses was done using direct immunofluorescent antibody assay from nasopharyngeal washing aspirate. In two RSV infection outbreaks (2006 and 2009), RSV antigen was detected in 6/30 patients. Five of six patients with RSV antigen were all treated with 0.2-0.4 g/kg intravenous immune globulin (IVIG) and specific antiviral therapy, oral ribavirin (20-25 mg/kg/day in three doses). Five patients recovered fully, although two were retreated due to recurrent (+) RSV antigen and respiratory symptoms within 2 weeks. We did not give oral ribavirin to one patient with (+) RSV antigen due to mild symptoms. All patients are alive and well. In contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in post bone marrow transplantation (BMT) period, is low when diagnosed and treated early enough. Oral ribavirin might be an option together with IVIG in the treatment of RSV especially when other forms of antivirals could not be obtained. This approach will make it possible to give the scheduled anti-neoplastic therapy on time.

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

    Directory of Open Access Journals (Sweden)

    Rungnapa Malasao

    Full Text Available 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.

  14. Respiratory syncytial virus can infect basal cells and alter human airway epithelial differentiation.

    Directory of Open Access Journals (Sweden)

    B David Persson

    Full Text Available Respiratory syncytial virus (RSV is a major cause of morbidity and mortality worldwide, causing severe respiratory illness in infants and immune compromised patients. The ciliated cells of the human airway epithelium have been considered to be the exclusive target of RSV, although recent data have suggested that basal cells, the progenitors for the conducting airway epithelium, may also become infected in vivo. Using either mechanical or chemical injury models, we have demonstrated a robust RSV infection of p63+ basal cells in air-liquid interface (ALI cultures of human bronchial epithelial cells. In addition, proliferating basal cells in 2D culture were also susceptible to RSV infection. We therefore tested the hypothesis that RSV infection of this progenitor cell would influence the differentiation status of the airway epithelium. RSV infection of basal cells on the day of seeding (MOI≤0.0001, resulted in the formation of an epithelium that showed a profound loss of ciliated cells and gain of secretory cells as assessed by acetylated α-tubulin and MUC5AC/MUC5B immunostaining, respectively. The mechanism driving the switch in epithelial phenotype is in part driven by the induced type I and type III interferon response that we demonstrate is triggered early following RSV infection. Neutralization of this response attenuates the RSV-induced loss of ciliated cells. Together, these data show that through infection of proliferating airway basal cells, RSV has the potential to influence the cellular composition of the airway epithelium. The resulting phenotype might be expected to contribute towards both the severity of acute infection, as well as to the longer-term consequences of viral exacerbations in patients with pre-existing respiratory diseases.

  15. Respiratory Syncytial Virus Coinfections With Rhinovirus and Human Bocavirus in Hospitalized Children

    Science.gov (United States)

    Calvo, Cristina; García-García, María Luz; Pozo, Francisco; Paula, Gallardo; Molinero, Mar; Calderón, Ana; González-Esguevillas, Mónica; Casas, Inmaculada

    2015-01-01

    Abstract It is not clearly established if coinfections are more severe than single viral respiratory infections. The aim of the study was to study and to compare simple infections and viral coinfections of respiratory syncytial virus (RSV) in hospitalized children. From September 2005 to August 2013, a prospective study was conducted on children younger than 14 years of age, admitted with respiratory infection to the Pediatric Department of the Severo Ochoa Hospital, in Spain. Specimens of nasopharyngeal aspirate were taken for virological study by using polymerase chain reaction, and clinical data were recorded. Simple RSV infections were selected and compared with double infections of RSV with rhinovirus (RV) or with human bocavirus (HBoV). In this study, 2993 episodes corresponding to 2525 children were analyzed. At least 1 virus was detected in 77% (2312) of the episodes. Single infections (599 RSV, 513 RV, and 81 HBoV) were compared with 120 RSV-RV and 60 RSV-HBoV double infections. The RSV-RV coinfections had fever (63% vs 43%; P < 0.001) and hypoxia (70% vs 43%; P < 0.001) more often than RV infections. Hypoxia was similar between single or dual infections (71%). Bronchiolitis was more frequent in the RSV simple group (P < 0.001). Pediatric intensive care unit admission was more common in RSV simple or RSV-RV groups than in the RV monoinfection (P = 0.042). Hospitalization was longer for both RSV simple group and RSV-HBoV coinfection, lasting about 1 day (4.7 vs 3.8 days; P < 0.001) longer than in simple HBoV infections. There were no differences in PICU admission. RSV single group was of a younger age than the other groups. Coinfections between RSV-RV and RSV-HBoV are frequent. Overall viral coinfections do not present greater severity, but have mixed clinical features. PMID:26496310

  16. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Eleanor R Gaunt

    2011-03-01

    Full Text Available Human respiratory syncytial virus (HRSV and human metapneumovirus (HMPV are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F protein, and the extremely diverse attachment (G glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.

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

    Science.gov (United States)

    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

  18. Elective cesarean delivery as a predisposing factor of respiratory syncytial virus bronchiolitis in children.

    Science.gov (United States)

    Shang, Xiaoli; Liabsuetrakul, Tippawan; Sangsupawanich, Pasuree; Xia, Xiaoling; He, Ping; Cao, Hong

    2014-08-01

    To investigate the effect of cesarean delivery and other predisposing factors of respiratory syncytial virus (RSV)-positive acute bronchiolitis in children. The case-control study was conducted in three main tertiary hospitals in Kunming, China between September 2012 and July 2013. Children with first episode of wheezing diagnosed as bronchiolitis and testedfor RSV were included RSV was detected by real-time reverse transcription polymerase chain reaction. Mode ofdelivery and characteristics of children, parents, and household were interviewed and analyzed with RSV-positive status by multiple logistic regression. Of 265 children, RSV-positive was found in 75.5%, and the majority of children (83.3%) were younger than 12 months. Compared to vaginal delivery, the odds of RSV-positive detection were double in children born by elective cesarean delivery (adjusted odds ratio 2.32; 95% confidence interval 1.19-4.52). Children aged less than 6 months, born in the rainy season, having maternal history of asthma and living in family that smoked more than 20 cigarettes per day were more likely to be RSV-positive. Children born by elective cesarean delivery increased the risk of RSV-positive acute bronchiolitis after adjusting for age, birth season, maternal asthma, and family smoking status.

  19. Trends in respiratory syncytial virus bronchiolitis hospitalizations in children less than 1 year: 2004-2012.

    Science.gov (United States)

    Sanchez-Luna, Manuel; Elola, Francisco J; Fernandez-Perez, Cristina; Bernal, Jose L; Lopez-Pineda, Adriana

    2016-01-01

    To analyze trends in health outcomes and the influence of risk factors in children under 1 year with acute bronchiolitis due to respiratory syncytial virus (RSV bronchiolitis). A risk-adjustment model for RSV bronchiolitis in-hospital mortality was also developed. Retrospective study of hospitalizations for RSV bronchiolitis in children aged bronchiolitis ranged between 6390 and 8637. The annual in-hospital mortality rate ranged from 120 (2004) to 69 (2012) per 100,000 hospitalizations and the mean length of stay decreased steadily from 6.5 to 5.2 days (p bronchiolitis were children without risk factors. The in-hospital mortality rate due to RSV bronchiolitis in children with risk factors was 18.8 times higher than non-high-risk children and, in adjusted analyses, the OR of in-hospital mortality due to RSV bronchiolitis was higher than that due to other causes. This study is a retrospective analysis, based on administrative data. It does not include data about pre- or in-hospital treatments, and has the limitations inherent in procedures for determining risk-adjusted mortality rates. Socioeconomic and environmental factors have not been considered in this study. RSV bronchiolitis is a leading cause of hospitalizations for infants under 1 year and has not shown incidence reduction over a 9 year period. Risk factors increase the in-hospital mortality risk and it is higher if the hospitalization cause is RSV bronchiolitis than any other reason.

  20. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children.

    Science.gov (United States)

    Papenburg, Jesse; Hamelin, Marie-Ève; Ouhoummane, Najwa; Carbonneau, Julie; Ouakki, Manale; Raymond, Frédéric; Robitaille, Lynda; Corbeil, Jacques; Caouette, Georges; Frenette, Lyne; De Serres, Gaston; Boivin, Guy

    2012-07-15

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading pediatric pathogens. However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections. We studied a prospective cohort of >1000 children aged 5 days, and pediatric intensive care unit admission. hMPV was identified in 58 of 305 outpatient children (19.0%) and 69 of 734 hospitalized children (9.4%), second only to RSV (48.2% and 63.6%, respectively). In multivariate regression analysis of hMPV cases, age <6 months and household crowding were associated with hospitalization. Among hospitalized patients, risk factors for severe hMPV disease were female sex, prematurity, and genotype B infection. Age <6 months, comorbidities, and household crowding were risk factors for RSV hospitalization; breast-feeding and viral coinfection were protective. Age <6 months and prematurity were associated with severe RSV cases among hospitalized children. hMPV and RSV severity risk factors may differ slightly. These findings will inform hMPV prevention strategies.

  1. Intranasal nanoemulsion-based inactivated respiratory syncytial virus vaccines protect against viral challenge in cotton rats.

    Science.gov (United States)

    O'Konek, Jessica J; Makidon, Paul E; Landers, Jeffrey J; Cao, Zhengyi; Malinczak, Carrie-Anne; Pannu, Jessie; Sun, Jennifer; Bitko, Vira; Ciotti, Susan; Hamouda, Tarek; Wojcinski, Zbigniew W; Lukacs, Nicholas W; Fattom, Ali; Baker, James R

    2015-01-01

    Respiratory Syncytial Virus is a leading cause of bronchiolitis and pneumonia in infants, the elderly and individuals with compromised immune systems. Despite decades of research, there is currently no available vaccine for RSV. Our group has previously demonstrated that intranasal immunization of mice with RSV inactivated by and adjuvanted with W805EC nanoemulsion elicits robust humoral and cellular immune responses, resulting in protection against RSV infection. This protection was achieved without the induction of airway hyper-reactivity or a Th2-skewed immune response. The cotton rat Sigmodon hispidus has been used for years as an excellent small animal model of RSV disease. Thus, we extended these rodent studies to the more permissive cotton rat model. Intranasal immunization of the nanoemulsion-adjuvanted RSV vaccines induced high antibody titers and a robust Th1-skewed cellular response. Importantly, vaccination provided sterilizing cross-protective immunity against a heterologous RSV challenge and did not induce marked or severe histological effects or eosinophilia in the lung after viral challenge. Overall, these data demonstrate that nanoemulsion-formulated whole RSV vaccines are both safe and effective for immunization in multiple animal models.

  2. Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze

    Directory of Open Access Journals (Sweden)

    Hodemaekers Hennie M

    2011-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW. Animal studies have suggested that interleukin (IL-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis. Methods This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%. Results Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02. The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs. Conclusion The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis.

  3. Human Respiratory Syncytial Virus: Role of Innate Immunity in Clearance and Disease Progression.

    Science.gov (United States)

    Farrag, Mohamed A; Almajhdi, Fahad N

    2016-01-01

    Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed.

  4. In silico analysis of amino acid variation in human respiratory syncytial virus: insights into immunodiagnostics.

    Science.gov (United States)

    Souza, Claudemir; Zanchin, Nilson It; Krieger, Marco A; Ludwig, Adriana

    2017-10-01

    The highly contagious nature of human respiratory syncytial virus (HRSV) and the gravity of its infection in newborns and vulnerable adults pose a serious public health problem. Thus, a rapid and sensitive diagnostic test for viral detection that can be implemented upon the first appearance of symptoms is needed. The genetic variation of the virus must be considered for immunodiagnostic purposes. To analyse HRSV genetic variation and discuss the possible consequences for capture immunoassay development. We performed a wide analysis of N, F and G protein variation based on the HRSV sequences currently available in the GenBank database. We also evaluated their similarity with homologous proteins from other viruses. The mean amino acid divergences for the N, F, and G proteins between HRSV-A and HRSV-B were determined to be approximately 4%, 10% and 47%, respectively. Due to their high conservation, assays based on the full-length N and F proteins may not distinguish HRSV from human metapneumovirus and other Mononegavirales viruses, and the full-length G protein would most likely produce false negative results due to its high divergence. We have identified specific regions in each of these three proteins that have higher potential to produce specific results, and their combined utilisation should be considered for immunoassay development.

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

    Science.gov (United States)

    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.

  6. On the Relative Role of Different Age Groups During Epidemics Associated With Respiratory Syncytial Virus.

    Science.gov (United States)

    Goldstein, Edward; Nguyen, Hieu H; Liu, Patrick; Viboud, Cecile; Steiner, Claudia A; Worby, Colin J; Lipsitch, Marc

    2018-01-04

    While circulation of respiratory syncytial virus (RSV) results in high rates of hospitalization, particularly among young children and elderly individuals, little is known about the role of different age groups in propagating annual RSV epidemics. We evaluate the roles played by individuals in different age groups during RSV epidemics in the United States between 2001 and 2012, using the previously defined relative risk (RR) statistic estimated from the hospitalization data from the Healthcare Cost and Utilization Project. Transmission modeling was used to examine the robustness of our inference method. Children aged 3-4 years and 5-6 years each had the highest RR estimate for 5 of 11 seasons included in this study, with RSV hospitalization rates in infants being generally higher during seasons when children aged 5-6 years had the highest RR estimate. Children aged 2 years had the highest RR estimate during one season. RR estimates in infants and individuals aged ≥11 years were mostly lower than in children aged 1-10 years. Highest RR values aligned with groups for which vaccination had the largest impact on epidemic dynamics in most model simulations. Our estimates suggest the prominent relative roles of children aged ≤10 years (particularly among those aged 3-6 years) in propagating RSV epidemics. These results, combined with further modeling work, should help inform RSV vaccination policies.

  7. Benefit and harm from immunity to respiratory syncytial virus: implications for treatment.

    Science.gov (United States)

    Habibi, Maximillian S; Openshaw, Peter J M

    2012-12-01

    Human respiratory syncytial virus (RSV) infection is a major cause of morbidity in children and of morbidity and mortality in elderly or immunocompromised adults. Given prophylactically, antibody can protect against infection, but natural levels are poorly protective. Vaccination may enhance disease, and there is no well tolerated and effective vaccine or antiviral treatment. Despite over 50 years of research, therapy remains nonspecific and supportive. Experimental human challenge in adult volunteers is beginning to elucidate the dynamics of viral shedding and causes of disease, but investigations of naturally infected children remain logistically challenging. RSV was known to bind several surface ligands, but the recent demonstration that nucleolin acts as a receptor for the RSV fusion protein was unexpected. Recent studies increasingly emphasize the relevance of innate immune responses and the dysregulation of inflammation as key factors in causing the pathological effects of infection. Studies in both human infants and mice indicate that interleukin-17 plays a role in some forms of RSV disease and regulatory T cells may be important in controlling inflammation. Improved understanding of the human immune response to RSV infection continues to be needed in order to accelerate the development of vaccines and new treatments for bronchiolitis.

  8. Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand.

    Science.gov (United States)

    Grimwood, K; Cohet, C; Rich, F J; Cheng, S; Wood, C; Redshaw, N; Cunningham, C W; Pearce, N; Kirman, J R

    2008-10-01

    This study assessed risk factors for respiratory syncytial virus (RSV) hospitalization and disease severity in Wellington, New Zealand. During the southern hemisphere winter months of 2003--2005, 230 infants aged < 24 months hospitalized with bronchiolitis were recruited. RSV was indentified in 141 (61%) infants. Comparison with data from all live hospital births from the same region (2003--2005) revealed three independent risk factors for RSV hospitalization: birth between February and July [adjusted risk ratio (aRR) 1.62, 95% confidence interval (CI) 1.5-2.29], gestation <37 weeks (aRR 2.29, 95% CI 1.48-3.56) and Māori ethnicity (aRR 3.64, 95% CI 2.27-5.85), or Pacific ethnicity (aRR 3.60, 95% CI 2.14-6.06). The high risk for Māori and Pacific infants was only partially accounted for by other known risk factors. This work highlights the importance of RSV disease in indigenous and minority populations, and identifies the need for further research to develop public health measures that can reduce health disparities.

  9. Successful prevention of respiratory syncytial virus nosocomial transmission following an enhanced seasonal infection control program.

    Science.gov (United States)

    Lavergne, V; Ghannoum, M; Weiss, K; Roy, J; Béliveau, C

    2011-01-01

    Respiratory syncytial virus (RSV) infections can be serious in severely immunocompromised patients. Use of a targeted infection control program (TICP) has been shown to reduce RSV nosocomial transmission. We evaluated the impact of an enhanced seasonal infection control program (ESICP) vs standard TICP in a hematology-oncology ward. TICP was applied from 1999 to 2001 and ESICP applied from 2001 to 2003. ESICP consisted of strict isolation for all patients admitted on the ward during the RSV season. We prospectively evaluated the incidence, related morbidity and mortality of nosocomial RSV in both field interventions. A total of 40 hospitalized RSV infections were documented. The cumulative incidence of nosocomial RSV during TICP and ESICP was respectively of 42.8 and 3.9 cases/1000 admissions (relative risk = 0.09). ESICP needed to be implemented on 26 admitted patients on our ward to prevent one RSV nosocomial case. Furthermore, implementation of ESICP prevented four pneumonias and two deaths per RSV season. We conclude that ESICP is significantly more efficient than TICP to reduce the occurrence of nosocomial RSV infections and its related morbidity and mortality in patients with hematological malignancy and recipients of hematopoietic SCT.

  10. Influence of respiratory syncytial virus strain differences on pathogenesis and immunity.

    Science.gov (United States)

    Melero, José A; Moore, Martin L

    2013-01-01

    Molecular epidemiology studies have provided convincing evidence of antigenic and sequence variability among respiratory syncytial virus (RSV) isolates. Circulating viruses have been classified into two antigenic groups (A and B) that correlate with well-delineated genetic groups. Most sequence and antigenic differences (both inter- and intra-groups) accumulate in two hypervariable segments of the G-protein gene. Sequences of the G gene have been used for phylogenetic analyses. These studies have shown a worldwide distribution of RSV strains with both local and global replacement of dominant viruses with time. Although data are still limited, there is evidence that strain variation may contribute to differences in pathogenicity. In addition, there is some but limited evidence that RSV variation may be, at least partially, immune (antibody) driven. However, there is the paradox in RSV that, in contrast to other viruses (e.g., influenza viruses) the epitopes recognized by the most effective RSV-neutralizing antibodies are highly conserved. In contrast, antibodies that recognize strain-specific epitopes are poorly neutralizing. It is likely that this apparent contradiction is due to the lack of a comprehensive knowledge of the duration and specificities of the human antibody response against RSV antigens. Since there are some data supporting a group- (or clade-) specific antibody response after a primary infection in humans, it may be wise to consider the incorporation of strains representative of groups A and B (or their antigens) in future RSV vaccine development.

  11. Evaluation of the Financial and Health Burden of Infants at Risk for Respiratory Syncytial Virus.

    Science.gov (United States)

    Blake, Stephanie McCallum; Tanaka, David; Bendz, Lisa M; Staebler, Suzanne; Brandon, Debra

    2017-08-01

    Respiratory syncytial virus (RSV) is the leading viral cause of death in infants younger than 1 year. In July 2014, the American Academy of Pediatrics (AAP) Committee on Infectious Diseases concluded that the "limited clinical benefit" for infants born at more than 29 weeks' gestation, together with the associated high cost of the immunoprophylaxis, no longer supported the routine use of palivizumab (Synagis). To evaluate the impact of the newly adopted AAP palivizumab prophylaxis administration on health and subsequent hospital costs of infants born between 29 and less than 32 weeks' gestation. A retrospective cohort analysis from a single institution across the duration of the study comparing the clinical and financial outcomes of infants (aged 29 weeks) managed after the 2014 AAP guidelines (POST) took effect. RSV-positive admissions were greater in the POST cohort versus the PRE cohort (P = .04). There were no readmission deaths due to RSV infection in either cohort. The number needed to treat to avoid a single RSV-positive hospitalization was 20 infants at an estimated palivizumab cost of $90,000 to avoid an estimated hospital cost of $29,000. Assessment of individual risk factors and their ability to predict severe RSV risk/disease, thus, would allow providers greater flexibility in determining need for prophylaxis therapy. Longitudinal evaluation of financial and clinical outcomes is needed to determine the impact of the 2014 AAP revised regulatory guidelines.

  12. A recombinant varicella vaccine harboring a respiratory syncytial virus gene induces humoral immunity.

    Science.gov (United States)

    Murakami, Kouki; Matsuura, Masaaki; Ota, Megumi; Gomi, Yasuyuki; Yamanishi, Koichi; Mori, Yasuko

    2015-11-09

    The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is highly efficient and causes few adverse events; therefore, it is used worldwide. We previously constructed recombinant vOka (rvOka) harboring the mumps virus gene. Immunizing guinea pigs with rvOka induced the production of neutralizing antibodies against the mumps virus and VZV. Here, we constructed recombinant vOka viruses containing either the respiratory syncytial virus (RSV) subgroup A fusion glycoprotein (RSV A-F) gene or RSV subgroup B fusion glycoprotein (RSV B-F) gene (rvOka-RSV A-F or rvOka-RSV B-F). Indirect immunofluorescence and Western blot analyses confirmed the expression of each recombinant RSV protein in virus-infected cells. Immunizing guinea pigs with rvOka-RSV A-F or rvOka-RSV B-F led to the induction of antibodies against RSV proteins. These results suggest that the current varicella vaccine genome can be used to generate custom-made vaccine vectors to develop the next generation of live vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    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 ATP 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.

  15. Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes

    Energy Technology Data Exchange (ETDEWEB)

    McLellan, Jason S.; Yang, Yongping; Graham, Barney S.; Kwong, Peter D. (NIAID)

    2011-09-16

    Respiratory syncytial virus (RSV) invades host cells via a type I fusion (F) glycoprotein that undergoes dramatic structural rearrangements during the fusion process. Neutralizing monoclonal antibodies, such as 101F, palivizumab, and motavizumab, target two major antigenic sites on the RSV F glycoprotein. The structures of these sites as peptide complexes with motavizumab and 101F have been previously determined, but a structure for the trimeric RSV F glycoprotein ectodomain has remained elusive. To address this issue, we undertook structural and biophysical studies on stable ectodomain constructs. Here, we present the 2.8-{angstrom} crystal structure of the trimeric RSV F ectodomain in its postfusion conformation. The structure revealed that the 101F and motavizumab epitopes are present in the postfusion state and that their conformations are similar to those observed in the antibody-bound peptide structures. Both antibodies bound the postfusion F glycoprotein with high affinity in surface plasmon resonance experiments. Modeling of the antibodies bound to the F glycoprotein predicts that the 101F epitope is larger than the linear peptide and restricted to a single protomer in the trimer, whereas motavizumab likely contacts residues on two protomers, indicating a quaternary epitope. Mechanistically, these results suggest that 101F and motavizumab can bind to multiple conformations of the fusion glycoprotein and can neutralize late in the entry process. The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit neutralizing antibodies and serve as a useful vaccine antigen.

  16. Development of Acquired Immunity following Repeated Respiratory Syncytial Virus Infections in Cotton Rats.

    Directory of Open Access Journals (Sweden)

    Yoshiaki Yamaji

    Full Text Available Respiratory syncytial virus (RSV infections occur every year worldwide. Most infants are infected with RSV by one year of age and are reinfected because immune responses after the first infection are too weak to protect against subsequent infections. In the present study, immune responses against RSV were investigated in order to obtain a better understanding of repetitive RSV infections in cotton rats. No detectable neutralizing antibody (NT was developed after the first infection, and the second infection was not prevented. The results of histological examinations revealed severe inflammation, viral antigens were detected around bronchial epithelial cells, and infectious viruses were recovered from lung homogenates. Following the second infection neutralizing antibodies were significantly elevated, and CD8+ cells were activated in response to RSV-F253-265. No viral antigens was detected thereafter in lung tissues and infectious viruses were not recovered. Similar results were obtained in the present study using the subgroups A and B. These results support the induction of humoral and cellular immune responses following repetitive infections with RSV; however, these responses were insufficient to eliminate viruses in the first and second infections.

  17. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Quistgaard, Esben M. [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Nordlund, Par [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Thanabalu, Thirumaran [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Torres, Jaume, E-mail: jtorres@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore)

    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 protein 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.

  18. The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

    Science.gov (United States)

    Murray, Gerard M; O'Neill, Rónan G; Lee, Alison M; McElroy, Máire C; More, Simon J; Monagle, Aisling; Earley, Bernadette; Cassidy, Joseph P

    2017-01-01

    The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (bovine sinus as it does in humans.

  19. Respiratory syncytial virus infection in children under one year of age hospitalized for acute respiratory diseases in Pelotas, RS

    Directory of Open Access Journals (Sweden)

    Macedo Silvia Elaine Cardozo

    2003-01-01

    Full Text Available INTRODUCTION: Acute respiratory diseases (ARDs are a major cause of infant morbidity and mortality. OBJECTIVE: The present case-controlled study investigated the hospitalizations by ARDs in children under one year of age and the association with the respiratory syncytial virus (RSV in za Pelotas, RS. METHODS: All children under one year of age hospitalized due to ARDs from August 1997 to July of 1998 were followed-up in the four hospitals of the city. A standardized questionnaire was applied to the children's mother regarding symptoms of the actual illness in addition to social and demographic variables, nutrition, and previous morbidity. The final diagnosis of ARDs was performed by an arbiter (a pediatrician based on the hospital records of the children and the data on the questionnaire. Nasopharyngeal secretions were collected for RSV detection by direct immunofluorescence. RESULTS: The study included 650 children and the annual incidence rate of hospital admissions for ARDs was 13.9%. Admissions showed a seasonal pattern with most of the hospitalizations occurring from July to October. The main causes of admission were: pneumonia (43.7%, bronchiolitis (31.0%, asthma (20.3%, influenza (3.5%, otitis media (0.8% and laryngitis (0.6%. The overall prevalence of RSV was 30.7%, with 40.2% in bronchiolitis, 28.6% in influenza, 27.4% in asthma, 26.3% in pneumonia, and 25% in otitis media. CONCLUSIONS: The results of the present study confirm the high morbidity of ARDs in childhood and the seasonal pattern of ARDs hospitalizations and their association with RSV infection.

  20. Respiratory Watch: Development of a provincial system for respiratory syncytial virus surveillance in Nova Scotia, 2005–2008

    Science.gov (United States)

    Al-Assam, Assaad; Langley, Joanne M; Sarwal, Shelly

    2009-01-01

    OBJECTIVE: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection in young children and is increasingly recognized as a cause of influenza-like illness in those older than 65 years of age. A surveillance system to provide timely local information about RSV activity in Nova Scotia (NS) is described. METHODS: A case report form was developed for weekly reporting of all laboratory isolates of RSV at diagnostic laboratories around the province. Laboratories were asked to send the forms by fax each Friday to the Nova Scotia Department of Health Promotion and Protection. Data were entered in Excel (Microsoft, USA) and aggregate results summarized by age, sex, health district and date of laboratory confirmation for 2005 to 2008. RESULTS: During three winter seasons (2005–2006, 2006–2007 and 2007–2008), there were 207, 350 and 186 isolates of RSV reported in NS, respectively. The average incidences of RSV in NS varied greatly by age, with the highest rates in infants younger than 24 months of age, and approaching 4000 cases per 100,000 population in infants up to five months of age. The duration of the RSV outbreak was approximately five to six months each year, but the month of onset varied. CONCLUSIONS: A RSV surveillance system was successfully established in NS that provides weekly data to the public health system, clinicians and infection control practitioners. The time of onset and severity of the RSV season varied over time. These data can be used to plan anti-RSV passive prophylaxis programs and infection control education, and distinguish RSV outbreaks from other viruses in acute care and long-term care settings. PMID:21119793

  1. Direct Inhibition of Cellular Fatty Acid Synthase Impairs Replication of Respiratory Syncytial Virus and Other Respiratory Viruses.

    Science.gov (United States)

    Ohol, Yamini M; Wang, Zhaoti; Kemble, George; Duke, Gregory

    2015-01-01

    Fatty acid synthase (FASN) catalyzes the de novo synthesis of palmitate, a fatty acid utilized for synthesis of more complex fatty acids, plasma membrane structure, and post-translational palmitoylation of host and viral proteins. We have developed a potent inhibitor of FASN (TVB-3166) that reduces the production of respiratory syncytial virus (RSV) progeny in vitro from infected human lung epithelial cells (A549) and in vivo from mice challenged intranasally with RSV. Addition of TVB-3166 to the culture medium of RSV-infected A549 cells reduces viral spread without inducing cytopathic effects. The antiviral effect of the FASN inhibitor is a direct consequence of reducing de novo palmitate synthesis; similar doses are required for both antiviral activity and inhibition of palmitate production, and the addition of exogenous palmitate to TVB-3166-treated cells restores RSV production. TVB-3166 has minimal effect on RSV entry but significantly reduces viral RNA replication, protein levels, viral particle formation and infectivity of released viral particles. TVB-3166 substantially impacts viral replication, reducing production of infectious progeny 250-fold. In vivo, oral administration of TVB-3166 to RSV-A (Long)-infected BALB/c mice on normal chow, starting either on the day of infection or one day post-infection, reduces RSV lung titers 21-fold and 9-fold respectively. Further, TVB-3166 also inhibits the production of RSV B, human parainfluenza 3 (PIV3), and human rhinovirus 16 (HRV16) progeny from A549, HEp2 and HeLa cells respectively. Thus, inhibition of FASN and palmitate synthesis by TVB-3166 significantly reduces RSV progeny both in vitro and in vivo and has broad-spectrum activity against other respiratory viruses. FASN inhibition may alter the composition of regions of the host cell membrane where RSV assembly or replication occurs, or change the membrane composition of RSV progeny particles, decreasing their infectivity.

  2. Distinct patterns of innate immune activation by clinical isolates of respiratory syncytial virus.

    Science.gov (United States)

    Levitz, Ruth; Gao, Yajing; Dozmorov, Igor; Song, Ran; Wakeland, Edward K; Kahn, Jeffrey S

    2017-01-01

    Respiratory syncytial virus (RSV) is a major respiratory pathogen of infants and young children. Multiple strains of both subgroup A and B viruses circulate during each seasonal epidemic. Genetic heterogeneity among RSV genomes, in large part due to the error prone RNA-dependent, RNA polymerase, could mediate variations in pathogenicity. We evaluated clinical strains of RSV for their ability to induce the innate immune response. Subgroup B viruses were used to infect human pulmonary epithelial cells (A549) and primary monocyte-derived human macrophages (MDM) from a variety of donors. Secretions of IL-6 and CCL5 (RANTES) from infected cells were measured following infection. Host and viral transcriptome expression were assessed using RNA-SEQ technology and the genomic sequences of several clinical isolates were determined. There were dramatic differences in the induction of IL-6 and CCL5 in both A549 cells and MDM infected with a variety of clinical isolates of RSV. Transcriptome analyses revealed that the pattern of innate immune activation in MDM was virus-specific and host-specific. Specifically, viruses that induced high levels of secreted IL-6 and CCL5 tended to induce cellular innate immune pathways whereas viruses that induced relatively low level of IL-6 or CCL5 did not induce or suppressed innate immune gene expression. Activation of the host innate immune response mapped to variations in the RSV G gene and the M2-1 gene. Viral transcriptome data indicated that there was a gradient of transcription across the RSV genome though in some strains, RSV G was the expressed in the highest amounts at late times post-infection. Clinical strains of RSV differ in cytokine/chemokine induction and in induction and suppression of host genes expression suggesting that these viruses may have inherent differences in virulence potential. Identification of the genetic elements responsible for these differences may lead to novel approaches to antiviral agents and vaccines.

  3. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Giselle A Funchal

    Full Text Available Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

  4. Respiratory syncytial virus interferon antagonist NS1 protein suppresses and skews the human T lymphocyte response.

    Directory of Open Access Journals (Sweden)

    Shirin Munir

    2011-04-01

    Full Text Available We recently demonstrated that the respiratory syncytial virus (RSV NS1 protein, an antagonist of host type I interferon (IFN-I production and signaling, has a suppressive effect on the maturation of human dendritic cells (DC that was only partly dependent on released IFN-I. Here we investigated whether NS1 affects the ability of DC to activate CD8+ and CD4+ T cells. Human DC were infected with RSV deletion mutants lacking the NS1 and/or NS2 genes and assayed for the ability to activate autologous T cells in vitro, which were analyzed by multi-color flow cytometry. Deletion of the NS1, but not NS2, protein resulted in three major effects: (i an increased activation and proliferation of CD8+ T cells that express CD103, a tissue homing integrin that directs CD8+ T cells to mucosal epithelial cells of the respiratory tract and triggers cytolytic activity; (ii an increased activation and proliferation of Th17 cells, which have recently been shown to have anti-viral effects and also indirectly attract neutrophils; and (iii decreased activation of IL-4-producing CD4+ T cells--which are associated with enhanced RSV disease--and reduced proliferation of total CD4+ T cells. Except for total CD4+ T cell proliferation, none of the T cell effects appeared to be due to increased IFN-I signaling. In the infected DC, deletion of the NS1 and NS2 genes strongly up-regulated the expression of cytokines and other molecules involved in DC maturation. This was partly IFN-I-independent, and thus might account for the T cell effects. Taken together, these data demonstrate that the NS1 protein suppresses proliferation and activation of two of the protective cell populations (CD103+ CD8+ T cells and Th17 cells, and promotes proliferation and activation of Th2 cells that can enhance RSV disease.

  5. Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease.

    Science.gov (United States)

    Su, Yung-Chang; Townsend, Dijana; Herrero, Lara J; Zaid, Ali; Rolph, Michael S; Gahan, Michelle E; Nelson, Michelle A; Rudd, Penny A; Matthaei, Klaus I; Foster, Paul S; Dent, Lindsay; Tripp, Ralph A; Lee, James; Simson, Ljubov; Mahalingam, Suresh

    2015-02-01

    Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load. This study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Arim; Suh, Sang-il; Seol, Hae-Young [Korea University College of Medicine, Department of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Son, Gyu-Ri; Lee, Nam-Joon [Korea University College of Medicine, Department of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University College of Medicine, Department of Radiology, Korea University Ansan Hospital, Gyeonggi-do (Korea, Republic of); Eun, Baik-Lin [Korea University College of Medicine, Department of Pediatrics, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2014-02-15

    Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients. (orig.)

  7. Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Nasr, S Z; Strouse, P J; Soskolne, E; Maxvold, N J; Garver, K A; Rubin, B K; Moler, F W

    2001-07-01

    To evaluate the effect of recombinant human deoxyribonuclease I (rhDNase) in shortening the length of the hospitalization and improving the chest radiographs (CXRs) in hospitalized infants with respiratory syncytial virus (RSV) infection as a result of its mucolytic properties. Randomized, double-blind, placebo-controlled investigation of 75 patients with RSV bronchiolitis. The study was conducted at the University of Michigan Medical Center and St. Joseph Mercy Hospital, both in Ann Arbor, MI. The respiratory rate, wheezing, and retraction difference scores, obtained by subtracting the hospital discharge score from the corresponding hospital admission score, show no difference between the two groups, but the CXR difference scores show that the rhDNase group improved by 0.46 while the placebo group worsened by 0.60 (p < 0.001). Analysis of covariance for the hospital discharge CXR score after adjusting for the hospital admission score for both groups was done. There was a difference in scores between the two groups, with adjusted mean for the study group of 2.03, and 2.76 for the placebo group (p < 0.001). Paired t test statistics in each of the two groups were computed. For the placebo group, the mean increase of 0.60 was significant (p = 0.02), and the mean decrease of 0.46 for the rhDNase group was also significant (p = 0.02). A one-way analysis of covariance with the hospital discharge CXR scores as the dependent variable and the hospital admission score as the covariate showed that there was a significant difference between the groups (p = 0.01). In patients with RSV bronchiolitis, there was significant improvement in the CXRs with the use of rhDNase compared to significant worsening in the placebo group. To our knowledge, this is the first report of the use of rhDNase to treat RSV bronchiolitis.

  8. Burden of respiratory syncytial virus infections in China: Systematic review and meta–analysis

    Directory of Open Access Journals (Sweden)

    Yaowen Zhang

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most important cause of acute respiratory tract infection (ARTI related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. A systematic search was performed in the Chinese BioMedical Database (CBM, China National Knowledge Infrastructure (CNKI, Wanfang database and PubMed to identify available published RSV studies in China. A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%. The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5% and lowest in those aged 16 years (2.8%, 95% CI 1.3–6.1. A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2% than in outpatients (14%, 95% CI 9.6–19.9%. RSV type A accounted for 63.1% (95% CI 52.3–72.8% of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.

  9. Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

    Directory of Open Access Journals (Sweden)

    Heinzmann Andrea

    2007-05-01

    Full Text Available Abstract Background Surfactant proteins (SP are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma. Methods We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. Results The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034. Conclusion Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

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

    Science.gov (United States)

    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.

  11. Molecular epidemiology and phylodynamics of the human respiratory syncytial virus fusion protein in northern Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin Chi

    Full Text Available BACKGROUND AND AIMS: The glycoprotein (G protein and fusion protein (F protein of respiratory syncytial virus (RSV both show genetic variability, but few studies have examined the F protein gene. This study aimed to characterize the molecular epidemiology and phylodynamics of the F protein gene in clinical RSV strains isolated in northern Taiwan from 2000-2011. METHODS: RSV isolates from children presenting with acute respiratory symptoms between July 2000 and June 2011 were typed based on F protein gene sequences. Phylogeny construction and evaluation were performed using the neighbor-joining (NJ and maximum likelihood (ML methods. Phylodynamic patterns in RSV F protein genes were analyzed using the Bayesian Markov Chain Monte Carlo framework. Selection pressure on the F protein gene was detected using the Datamonkey website interface. RESULTS: From a total of 325 clinical RSV strains studied, phylogenetic analysis showed that 83 subgroup A strains (RSV-A could be further divided into three clusters, whereas 58 subgroup B strains (RSV-B had no significant clustering. Three amino acids were observed to differ between RSV-A and -B (positions 111, 113, and 114 in CTL HLA-B*57- and HLA-A*01-restricted epitopes. One positive selection site was observed in RSV-B, while none was observed in RSV-A. The evolution rate of the virus had very little change before 2000, then slowed down between 2000 and 2005, and evolved significantly faster after 2005. The dominant subtypes of RSV-A in each epidemic were replaced by different subtypes in the subsequent epidemic. CONCLUSIONS: Before 2004, RSV-A infections were involved in several small epidemics and only very limited numbers of strains evolved and re-emerged in subsequent years. After 2005, the circulating RSV-A strains were different from those of the previous years and continued evolving through 2010. Phylodynamic pattern showed the evolutionary divergence of RSV increased significantly in the recent 5

  12. Molecular epidemiology and disease severity of human respiratory syncytial virus in Vietnam.

    Directory of Open Access Journals (Sweden)

    Dinh Nguyen Tran

    Full Text Available Respiratory syncytial virus (RSV is a major cause of acute respiratory infections (ARIs in children worldwide and can cause high mortality, especially in developing countries. However, information on the clinical and molecular characteristics of RSV infection in developing countries is limited. From April 2010 to May 2011, 1,082 nasopharyngeal swabs were collected from children with ARI admitted to the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for RSV and genotyped by reverse transcription-PCR and sequencing. Demographic and clinical data was also recorded. RSV was found in 23.8% (257/1,082 of samples. RSV A was the dominant subgroup, accounting for 91.4% (235/257, followed by RSV B, 5.1% (13/257, and 9 cases (3.5% were mixed infection of these subgroups. The phylogenetic analysis revealed that all group A strains belonged to the GA2 genotype. All group B strains belonged to the recently identified BA genotype, and further clustered into 2 recently described subgenotypes BA9 and BA10. One GA2 genotype strain had a premature stop codon which shortened the G protein length. RSV infection was significantly associated with younger age and higher severity score than those without. Co-infection with other viruses did not affect disease severity. RSV A caused more severe disease than RSV B. The results from this study will not only contribute to the growing database on the molecular diversity of RSV circulating worldwide but may be also useful in clinical management and vaccine development.

  13. Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.

    Science.gov (United States)

    Carroll, Kecia N; Gebretsadik, Tebeb; Escobar, Gabriel J; Wu, Pingsheng; Li, Sherian Xu; Walsh, Eileen M; Mitchel, Ed; Sloan, Chantel D; Dupont, William D; Hartert, Tina V

    2017-01-01

    Respiratory syncytial virus (RSV) lower respiratory tract infection is implicated in asthma development. RSV immunoprophylaxis during infancy is efficacious in preventing RSV-related hospitalizations and has been associated with decreased wheezing in the first years of life. We investigated whether greater adherence to immunoprophylaxis in infants at high risk for severe RSV would be associated with decreased childhood asthma. We conducted a retrospective cohort investigation including children born from 1996-2003 who were enrolled in Kaiser Permanente Northern California or Tennessee Medicaid and eligible to receive RSV immunoprophylaxis. Asthma was defined at 4.5 to 6 years of age by using asthma-specific health care visits and medication fills. We classified children into immunoprophylaxis eligibility groups and calculated adherence (percentage receipt of recommended doses). We used a set of statistical strategies (multivariable logistic regression and propensity score [PS]-adjusted and PS-matched analyses) to overcome confounding by medical complexity because infants with higher adherence (≥70%) have higher prevalence of chronic lung disease, lower birth weight, and longer nursery stays. By using multivariable logistic regression and PS-adjusted models in the combined group, higher adherence to RSV immunoprophylaxis was not associated with decreased asthma. However, in PS-matched analysis, treated children with 70% or greater adherence had decreased odds of asthma compared with those with 20% or less adherence (odds ratio, 0.62; 95% CI, 0.50-0.78). This investigation of RSV immunoprophylaxis in high-risk children primarily found nonsignificant associations on prevention of asthma in specific preterm groups. Our findings highlight the need for larger studies and prospective cohorts and provide estimates of potential preventive effect sizes in high-risk children. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc

  14. Distinct patterns of innate immune activation by clinical isolates of respiratory syncytial virus

    Science.gov (United States)

    Levitz, Ruth; Wakeland, Edward K.

    2017-01-01

    Respiratory syncytial virus (RSV) is a major respiratory pathogen of infants and young children. Multiple strains of both subgroup A and B viruses circulate during each seasonal epidemic. Genetic heterogeneity among RSV genomes, in large part due to the error prone RNA-dependent, RNA polymerase, could mediate variations in pathogenicity. We evaluated clinical strains of RSV for their ability to induce the innate immune response. Subgroup B viruses were used to infect human pulmonary epithelial cells (A549) and primary monocyte-derived human macrophages (MDM) from a variety of donors. Secretions of IL-6 and CCL5 (RANTES) from infected cells were measured following infection. Host and viral transcriptome expression were assessed using RNA-SEQ technology and the genomic sequences of several clinical isolates were determined. There were dramatic differences in the induction of IL-6 and CCL5 in both A549 cells and MDM infected with a variety of clinical isolates of RSV. Transcriptome analyses revealed that the pattern of innate immune activation in MDM was virus-specific and host-specific. Specifically, viruses that induced high levels of secreted IL-6 and CCL5 tended to induce cellular innate immune pathways whereas viruses that induced relatively low level of IL-6 or CCL5 did not induce or suppressed innate immune gene expression. Activation of the host innate immune response mapped to variations in the RSV G gene and the M2-1 gene. Viral transcriptome data indicated that there was a gradient of transcription across the RSV genome though in some strains, RSV G was the expressed in the highest amounts at late times post-infection. Clinical strains of RSV differ in cytokine/chemokine induction and in induction and suppression of host genes expression suggesting that these viruses may have inherent differences in virulence potential. Identification of the genetic elements responsible for these differences may lead to novel approaches to antiviral agents and vaccines

  15. Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years

    Science.gov (United States)

    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

  16. Respiratory syncytial virus outbreak in neonatal intensive care unit: Impact of infection control measures plus palivizumab use

    Directory of Open Access Journals (Sweden)

    Silva Camila de A

    2012-05-01

    Full Text Available Abstract Background The occurrence of a respiratory syncytial virus (RSV outbreak in a Neonatal Intensive Care Unit (NICU is related to unfavorable outcomes, as this infection can lead to respiratory distress and death in premature in infants. Report the successful control of an outbreak that occurred in April 2010 in a NICU. Methods After the index case, of 18 premature infants placed in the same room 10 infants were infected. Of those 10, 6 developed mild to moderate respiratory symptoms, 4 persisted asymptomatic and no death occurred. Contact and respiratory precautions were rapidly initiated, the infants were cohorted in 3 different rooms and palivizumab was administered to all contacts. Results The outbreak was controlled and no new cases were subsequently indentified. Conclusion Standard infection control measures plus palivizumab prophylaxis were efficient in rapid control of the outbreak.

  17. The burden of hospitalized lower respiratory tract infection due to respiratory syncytial virus in rural Thailand.

    Directory of Open Access Journals (Sweden)

    Alicia M Fry

    Full Text Available BACKGROUND: We describe the epidemiology of hospitalized RSV infections for all age groups from population-based surveillance in two rural provinces in Thailand. METHODS: From September 1, 2003 through December 31, 2007, we enrolled hospitalized patients with acute lower respiratory tract illness, who had a chest radiograph ordered by the physician, from all hospitals in SaKaeo and Nakhom Phanom Provinces. We tested nasopharyngeal specimens for RSV with reverse transcriptase polymerase chain reaction (RT-PCR assays and paired-sera from a subset of patients with IgG enzyme immunoassay. Rates were adjusted for enrollment. RESULTS: Among 11,097 enrolled patients, 987 (8.9% had RSV infection. Rates of hospitalized RSV infection overall (and radiographically-confirmed pneumonia were highest among children aged<1 year: 1,067/100,000 (534/100,000 radiographically-confirmed pneumonia and 1-4 year: 403/100,000 (222/100,000, but low among enrolled adults aged≥65 years: 42/100,000. Age<1 year (adjusted odds ratio [aOR]=13.2, 95% confidence interval [CI] 7.7, 22.5 and 1-4 year (aOR=8.3, 95% CI 5.0, 13.9 were independent predictors of hospitalized RSV infection. CONCLUSIONS: The incidence of hospitalized RSV lower respiratory tract illness among children<5 years was high in rural Thailand. Efforts to prevent RSV infection could substantially reduce the pneumonia burden in children aged<5 years.

  18. A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats

    NARCIS (Netherlands)

    Kamphuis, Tobias; Stegmann, Toon; Meijerhof, Tjarko; Wilschut, Jan; de Haan, Aalzen

    2013-01-01

    Background Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR)

  19. Confirmation of an Association Between Single Nucleotide Polymorphisms in the VDR Gene With Respiratory Syncytial Virus Related Disease in South African Children

    NARCIS (Netherlands)

    Kresfelder, T. L.; Janssen, R.; Bont, L.; Venter, M.

    2011-01-01

    Respiratory syncytial virus is a leading cause of lower respiratory tract infection in infants. Disease severity has been linked to host immune responses and polymorphisms in genes associated with innate immunity. A large-scale genetics study of single nucleotide polymorphisms (SNPs) in children in

  20. Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands

    NARCIS (Netherlands)

    Shafique, Muhammad; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    Respiratory syncytial virus (RSV) infection is the most important viral cause of severe respiratory disease in infants and children worldwide and also forms a serious threat in the elderly. The development of RSV vaccine, however, has been hampered by the disastrous outcome of an earlier trial using

  1. Recombinant subgroup B human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats

    NARCIS (Netherlands)

    K. Lemon (Ken); D.T. Nguyen (Tien); M. Ludlow (Martin); L.J. Rennick (Linda); S. Yüksel (Selma); G. van Amerongen (Geert); S. McQuaid (Stephen); B.K. Rima (Bert); R.L. de Swart (Rik); W.P. Duprex (Paul)

    2015-01-01

    textabstractHuman respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro

  2. Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau

    DEFF Research Database (Denmark)

    Stensballe, L G; Kofoed, P E; Nante, E J

    2000-01-01

    Respiratory syncytial virus (RSV) is probably the single major cause of lower respiratory infection (LRI) among infants worldwide. Its relative importance may be underestimated, as the diagnosis is based on antigen detection and antigen may only be detectable in the early phase of infection. We...

  3. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Høgh, Mette; Nordbø, Svein

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children...

  4. Seroprevalence of viral and bacterial diseases among the bovines in Himachal Pradesh, India

    Directory of Open Access Journals (Sweden)

    Shailja Katoch

    2017-12-01

    Full Text Available Aim: The study was designed to measure the seroprevalence of viral and bacterial diseases: Infectious bovine rhinotracheitis, bovine viral diarrhea, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, brucellosis, and paratuberculosis among bovine of Himachal Pradesh during the year 2013-2015. Materials and Methods: The serum samples were collected from seven districts of state, namely, Bilaspur, Kangra, Kinnaur, Lahul and Spiti, Mandi, Sirmour, and Solan. The samples were screened using indirect ELISA kits to measure the seroprevalence of viral and bacterial diseases. Results: The overall seroprevalence of infectious bovine rhinotracheitis was 24.24%, bovine viral diarrhea 1.52%, bovine leukemia 9.09%, bovine parainfluenza 57.58%, bovine respiratory syncytial disease 50%, brucellosis 19.69%, and paratuberculosis 9.09% in Himachal Pradesh. The seroprevalence of bovine rhinotracheitis, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, and paratuberculosis in the state varied significantly (p0.01. Multiple seropositivity has been observed in this study. Bovine parainfluenza virus 3 was observed commonly in mixed infection with almost all viruses and bacteria under study. Conclusion: The viral and bacterial diseases are prevalent in the seven districts of Himachal Pradesh investigated in the study. Therefore, appropriate management practices and routine vaccination programs should be adopted to reduce the prevalence of these diseases.

  5. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

    Science.gov (United States)

    Chen, Man; Joyce, M. Gordon; Kong, Wing-Pui; Chuang, Gwo-Yu; Ko, Kiyoon; Kumar, Azad; Silacci, Chiara; Thom, Michelle; Salazar, Andres M.; Corti, Davide; Lanzavecchia, Antonio; Taylor, Geraldine; Mascola, John R.; Graham, Barney S.

    2017-01-01

    Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but

  6. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Mallika Sastry

    Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

  7. Respiratory Syncytial Virus Attachment Glycoprotein Contribution to Infection Depends on the Specific Fusion Protein.

    Science.gov (United States)

    Meng, Jia; Hotard, Anne L; Currier, Michael G; Lee, Sujin; Stobart, Christopher C; Moore, Martin L

    2015-10-14

    Human respiratory syncytial virus (RSV) is an important pathogen causing acute lower respiratory tract disease in children. The RSV attachment glycoprotein (G) is not required for infection, as G-null RSV replicates efficiently in several cell lines. Our laboratory previously reported that the viral fusion (F) protein is a determinant of strain-dependent pathogenesis. Here, we hypothesized that virus dependence on G is determined by the strain specificity of F. We generated recombinant viruses expressing G and F, or null for G, from the laboratory A2 strain (Katushka RSV-A2GA2F [kRSV-A2GA2F] and kRSV-GstopA2F) or the clinical isolate A2001/2-20 (kRSV-2-20G2-20F and kRSV-Gstop2-20F). We quantified the virus cell binding, entry kinetics, infectivity, and growth kinetics of these four recombinant viruses in vitro. RSV expressing the 2-20 G protein exhibited the greatest binding activity. Compared to the parental viruses expressing G and F, removal of 2-20 G had more deleterious effects on binding, entry, infectivity, and growth than removal of A2 G. Overall, RSV expressing 2-20 F had a high dependence on G for binding, entry, and infection. RSV is the leading cause of childhood acute respiratory disease requiring hospitalization. As with other paramyxoviruses, two major RSV surface viral glycoproteins, the G attachment protein and the F fusion protein, mediate virus binding and subsequent membrane fusion, respectively. Previous work on the RSV A2 prototypical strain demonstrated that the G protein is functionally dispensable for in vitro replication. This is in contrast to other paramyxoviruses that require attachment protein function as a prerequisite for fusion. We reevaluated this requirement for RSV using G and F proteins from clinical isolate 2-20. Compared to the laboratory A2 strain, the G protein from 2-20 had greater contributions to virus binding, entry, infectivity, and in vitro growth kinetics. Thus, the clinical isolate 2-20 F protein function depended

  8. A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation.

    Science.gov (United States)

    Levin, Daniel L; Garg, Abhinav; Hall, Leila J; Slogic, Scott; Jarvis, J Dean; Leiter, James C

    2008-11-01

    To study patients with respiratory syncytial virus bronchiolitis in respiratory failure to make specific measurements reflecting airway resistance before and after treatment with commonly used agents. We hypothesized that racemic epinephrine would decrease airways resistance more effectively than levalbuterol, and levalbuterol would decrease airways resistance more effectively than racemic albuterol. Normal saline was used as a control. Prospective, randomized, controlled, blinded study. Tertiary Pediatric Intensive Care Unit in a University affiliated hospital in the northeastern United States. Twenty-two patients with respiratory syncytial virus bronchiolitis and in respiratory failure were enrolled. All were intubated and ventilated in a volume control mode and sedated. In a randomized, blinded fashion patients were given four agents: norepinephrine, levalbuterol, racemic albuterol, and normal saline at 6 hr intervals. As indicators of bronchodilation, peak inspiratory pressure and inspiratory respiratory system resistance were measured before and 20 mins after each agent was given. Thus, each patient acted as his/her own control. There were small but statistically significant decreases in peak inspiratory pressure after racemic epinephrine treatment, levalbuterol, and racemic albuterol. There was no change in peak inspiratory pressure after inhaled normal saline. Inspiratory respiratory system resistance fell significantly after all treatments, including saline. Heart rate rose significantly after inhaled bronchodilator treatments (p < 0.05 for all treatments). Similar statistically significant bronchodilation occurred after all three bronchodilators as indicated by a decrease in peak inspiratory pressure and respiratory system resistance, but these changes were small and probably clinically insignificant. However, side effects of bronchodilators, such as tachycardia, also occurred, and these may be clinically significant. Thus the benefit of bronchodilator

  9. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice.

    Directory of Open Access Journals (Sweden)

    Robert F Foronjy

    Full Text Available 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.

  10. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis

    Directory of Open Access Journals (Sweden)

    Skjaeret Camilla

    2006-12-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease. Results Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27 and the highly downregulated gene Charcot-Leyden crystal protein (CLC to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray. Conclusion The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity.

  11. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  12. Oxidative stress and inflamatory plasma biomarkers in respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Moreno-Solís, Gloria; Dela Torre-Aguilar, María José; Torres-Borrego, Javier; Llorente-Cantarero, Francisco Jesus; Fernández-Gutiérrez, Fernando; Gil-Campos, Mercedes; Túnez-Fiñana, Isaac; Pérez-Navero, Juan Luis

    2017-11-01

    Oxidative stress (OS) plays a crucial role in the pathogenesis of inflammatory lung diseases. (i) We determined whether acute bronchiolitis (AB) caused by respiratory syncytial virus (RSV) induced OS; (ii) assessed whether OS biomarkers correlated with the severity of RSV-AB; and (iii) studied whether the levels of interleukins are associated with OS biomarkers. We performed an observational study by comparing healthy infants (Group 1) with RSV-AB infants, classified as Group 2 (pulse oximetry (SpO2 ) >93%), and Group 3 (SpO2  ≤ 92%), which needed oxygen therapy. Blood samples were collected to determine the levels of lipid peroxidation (LPO) products (LPO), total glutathione (TG), oxidised glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), interleukins (ILs) IL-10, IL-6, IL-8, interferon-gamma (IFNγ), tumour necrosis factor-alpha (TNFα) and macrophage inflammatory proteins (MIP α and MIP β). Forty-six RSV-AB infants (47% needed oxygen therapy) and 27 healthy infants were included. The GSH/GSSG ratio was lower in RSV-AB infants than in Group 1 (P<0.001). GSSG and GPx were significantly higher in Group 3. GSSG predicted the need for oxygen therapy with an optimal cut-off point of 15 µM/g for haemoglobin. The GSH/GSSG ratio negatively correlated with IL-6 (P: 0.014), IL-8 (P: 0.014) and IL-10 (P: 0.033). Group 3 exhibited a direct correlation between GPx and IL-10 levels (P: 0.024) and between LPO and MIP β (P: 0.003). RSV induced OS in AB. An increase in GSSG correlated with the disease severity in the infants. OS may contribute to the pathogenesis of RSV-AB. © 2015 John Wiley & Sons Ltd.

  13. DNGR-1 is dispensable for CD8+ T-cell priming during respiratory syncytial virus infection.

    Science.gov (United States)

    Durant, Lydia R; Pereira, Catherine; Boakye, Aime; Makris, Spyridon; Kausar, Fahima; Goritzka, Michelle; Johansson, Cecilia

    2014-08-01

    During respiratory syncytial virus (RSV) infection CD8(+) T cells both assist in viral clearance and contribute to immunopathology. CD8(+) T cells recognize viral peptides presented by dendritic cells (DCs), which can directly present viral antigens when infected or, alternatively, "cross-present" antigens after endocytosis of dead or dying infected cells. Mouse CD8α(+) and CD103(+) DCs excel at cross-presentation, in part because they express the receptor DNGR-1 that detects dead cells by binding to exposed F-actin and routes internalized cell debris into the cross-presentation pathway. As RSV causes death in infected epithelial cells, we tested whether cross-presentation via DNGR-1 is necessary for CD8(+) T-cell responses to the virus. DNGR-1-deficient or wild-type mice were intranasally inoculated with RSV and the magnitude of RSV-specific CD8(+) T-cell induction was measured. We found that during live RSV infection, cross-presentation via DNGR-1 did not have a major role in the generation of RSV-specific CD8(+) T-cell responses. However, after intranasal immunization with dead cells infected with RSV, a dependence on DNGR-1 for RSV-specific CD8(+) T-cell responses was observed, confirming the ascribed role of the receptor. Thus, direct presentation by DCs may be the major pathway initiating CD8(+) T-cell responses to RSV, while DNGR-1-dependent cross-presentation has no detectable role. © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease.

    Science.gov (United States)

    Resch, B; Kurath-Koller, S; Hahn, J; Raith, W; Köstenberger, M; Gamillscheg, A

    2016-07-01

    The purpose of this investigation was to analyze the burden of respiratory syncytial virus (RSV)-related hospitalizations in infants and children with congenital heart disease (CHD) over three consecutive RSV seasons. Retrospectively, all children with hemodynamically significant (HS-CHD) and not significant (HNS-CHD) CHD born between 2004 and 2008 at a tertiary care university hospital and identified by ICD-10 diagnoses were included. Data on RSV-related hospitalizations over the first three years of life covering at least three RSV seasons (November-April) were analyzed. The overall incidence of RSV-related hospitalization was 9.6 % (58/602), without a statistically significant difference between HS-CHD and HNS-CHD (7.3 % vs. 10.4 %; p = 0.258). Recommendation of palivizumab prophylaxis did not influence the RSV hospitalization rates between groups. Patients with HS-CHD and early surgery were significantly less often hospitalized due to RSV compared to those with delayed surgery (1.3 % vs. 14.3 %; p = 0.003). The median duration of hospitalization was 8.5 days (HS-CHD: 14 vs. 7 days; p = 0.003). Thirteen patients (22.4 %) were admitted to the intensive care unit (ICU), for a median of 10 days. The median age at admission was 2 months, with a significant difference between HS-CHD and HNS-CHD (6 vs. 2 months; p = 0.001). The majority (97 %) of RSV-related hospitalizations occurred before 12 months of age. Patients with HS-CHD had a significantly more severe course of RSV disease and were older at the time of hospitalization. Early surgery seemed to significantly reduce the risk of RSV hospitalization during the first RSV season.

  15. Respiratory syncytial virus hospitalization trends in infants with chronic lung disease of infancy, 1998-2008.

    Science.gov (United States)

    Groothuis, Jessie R; Fryzek, Jon P; Makari, Doris; Steffey, Duane; Martone, William J

    2011-01-01

    Infants with chronic lung disease of infancy (CLDI) are at high risk for severe respiratory syncytial virus (RSV) illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged launch of palivizumab. Data from the United States National Hospital Discharge Survey, a multistage systematic survey sample of US hospitals, were assembled. We defined RSVH using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Quarterly rates of RSVH were assessed for children with CLDI (ICD-9-CM code 770.7) and calculated between 1998 and 2008. Because RSV may be miscoded, the analysis was repeated after expanding the definition of RSVH to include all acute bronchitis and acute bronchiolitis (ABH) (ICD-9-CM = 466). Trends were described using linear regression with seasonal indicators included in the model. On average, about 966 RSVH (range 98-1373 RSVH) per year were found for children <2 years with CLDI in the USA between 1998 and 2008. Over the 11-year period, the predicted rate of RSVH statistically significantly decreased by 48% (from 93.78 to 49.06 RSVH per 1 million children) (P = 0.013). Addition of ABH resulted in a nonstatisically significant decrease of 32% over the 10-year period (P = 0.102). These results suggest that there has been a decrease in the rate of RSVH in infants with CLDI between 1998 and 2008. The reasons for this decrease may include improved neonatal intensive care unit and outpatient management of CLDI, and possibly increased use of palivizumab in this high-risk population.

  16. Specific dietary oligosaccharides increase Th1 responses in a mouse respiratory syncytial virus infection model.

    Science.gov (United States)

    Schijf, Marcel A; Kruijsen, Debby; Bastiaans, Jacqueline; Coenjaerts, Frank E J; Garssen, Johan; van Bleek, Grada M; van't Land, Belinda

    2012-11-01

    Breast feeding reduces the risk of developing severe respiratory syncytial virus (RSV) infections in infants. In addition to maternal antibodies, other immune-modulating factors in human milk contribute to this protection. Specific dietary prebiotic oligosaccharides, similar to oligosaccharides present in human milk, were evaluated in a C57BL/6 mouse RSV infection model. During primary RSV infection, increased numbers of RSV-specific CD4(+) T cells producing gamma interferon (IFN-γ) were found in the lungs at days 8 to 10 postinfection in mice receiving diet containing short-chain galactooligosacharides, long-chain fructooligosaccharides, and pectin-derived acidic oligosaccharides (termed scGOS/lcFOS/pAOS). In a Th2-skewed formalin-inactivated (FI)-RSV vaccination model, the prebiotic diet reduced RSV-specific Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13)-producing CD4(+) T cells in the lung and the magnitude of airway eosinophilia at day 4 and 6 after infection. This was accompanied by a decreased influx of inflammatory dendritic cells (CD11b(+)/CD11c(+)) and increased numbers of IFN-γ-producing CD4(+) and CD8(+) T cells at day 8 after viral challenge. These findings suggest that specific dietary oligosaccharides can influence trafficking and/or effector functions of innate immune, CD4(+), and CD8(+) T cell subsets in the lungs of RSV-infected mice. In our models, scGOS/lcFOS/pAOS had no effect on weight but increased viral clearance in FI-RSV-vaccinated mice 8 days after infection. The increased systemic Th1 responses potentiated by scGOS/lcFOS/pAOS might contribute to an accelerated Th1/Th2 shift of the neonatal immune system, which might favor protective immunity against viral infections with a high attack rate in early infancy, such as RSV.

  17. Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

    Science.gov (United States)

    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

  18. Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Xavier Roux

    Full Text Available BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N, has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS. METHODOLOGY AND PRINCIPAL FINDINGS: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G. Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8(+ T cells and IFN-gamma-producing CD4(+ T cells. CONCLUSIONS/SIGNIFICANCE: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

  19. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  20. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Directory of Open Access Journals (Sweden)

    Kelechi Ugonna

    Full Text Available We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  1. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

    Directory of Open Access Journals (Sweden)

    Ngama Mwanajuma

    2010-01-01

    Full Text Available Abstract 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.

  2. A neutralization assay for respiratory syncytial virus using a quantitative PCR-based endpoint assessment

    Science.gov (United States)

    2013-01-01

    Background Few studies have used quantitative polymerase chain reaction (qPCR) as an approach to measure virus neutralization assay endpoints. Its lack of use may not be surprising considering that sample nucleic acid extraction and purification can be expensive, labor-intensive, and rate-limiting. Methods Virus/antibody mixtures were incubated for one hour at 37°C and then transferred to Vero cell monolayers in a 96-well plate format. At 24 (or 48) hours post-infection, we used a commercially available reagent to prepare cell lysates amenable to direct analysis by one-step SYBR Green quantitative reverse transcription PCR using primers specific for the RSV-N gene, thereby obviating the need for cumbersome RNA extraction and purification. The neutralization titer was defined as the reciprocal of the highest dilution needed to inhibit the PCR signal by 90% when compared with the mean value observed in virus control wells in the absence of neutralizing antibodies. Results We have developed a qPCR-based neutralization assay for human respiratory syncytial virus. Due to the sensitivity of qPCR in detecting virus replication, endpoints may be assessed as early as 24 hours post-infection. In addition, the dynamic range of qPCR provides a basis for the assay to be relatively robust to perturbations in input virus dose (i.e., the assay is in compliance with the Percentage Law). Conclusions This qPCR-based neutralization assay is suitable for automated high-throughput applications. In addition, our experimental approach may be generalizable for the rapid development of neutralization assays for other virus families. PMID:23767960

  3. Experimental animal model for analyzing immunobiological responses following vaccination with formalin-inactivated respiratory syncytial virus.

    Science.gov (United States)

    Sawada, Akihito; Nakayama, Tetsuo

    2016-04-01

    Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine was developed in the 1960s. However, this vaccine does not prevent infection in RSV-naïve recipients and has the paradoxical effect of increasing the severity of RSV illness following natural infection, which has been a major obstacle to developing RSV vaccines. Several experimental animal models for determining the cause of the severe symptoms in FI-RSV recipients have been developed. In the present study, cotton rats immunized with FI-RSV were challenged with RSV and histopathological findings and recovery of infectious virus were studied. Copy numbers of mRNA of Th1 and Th2 cytokines were measured in lung tissues to gain better understanding of their immune responses. Infiltration of inflammatory cells and prominent interstitial pneumonitis were observed in the FI-RSV group, as was induction of mRNA of Th2 cytokines such as IL-4, IL-10, IL-13 and RANTES. Rats immunized with recombinant measles virus expressing the RSV F protein (MVAIK/RSV/F) and those treated with anti-RSV mAb (palivizumab) showed very mild interstitial pneumonitis. Amounts of mRNA of IL-1β, IFN-γ and IL-4 were higher in the MVAIK/RSV/F group. Administration of palivizumab before RSV challenge decreased the severity of interstitial pneumonitis in the FI-RSV group. FI-RSV induced skewed Th2 responses, resulting in severe inflammatory responses. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  4. Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    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) 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.)

  5. Protection against respiratory syncytial virus by inactivated influenza virus carrying a fusion protein neutralizing epitope in a chimeric hemagglutinin.

    Science.gov (United States)

    Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul; Lee, Young-Tae; Kim, Yu-Jin; Lee, F Eun-Hyung; Kang, Sang-Moo

    2016-04-01

    A desirable vaccine against respiratory syncytial virus (RSV) should induce neutralizing antibodies without eliciting abnormal T cell responses to avoid vaccine-enhanced pathology. In an approach to deliver RSV neutralizing epitopes without RSV-specific T cell antigens, we genetically engineered chimeric influenza virus expressing RSV F262-276 neutralizing epitopes in the globular head domain as a chimeric hemagglutinin (HA) protein. Immunization of mice with formalin-inactivated recombinant chimeric influenza/RSV F262-276 was able to induce RSV protective neutralizing antibodies and lower lung viral loads after challenge. Formalin-inactivated RSV immune mice showed high levels of pulmonary inflammatory cytokines, macrophages, IL-4-producing T cells, and extensive histopathology. However, RSV-specific T cell responses and enhancement of pulmonary histopathology were not observed after RSV infection of inactivated chimeric influenza/RSV F262-276. This study provides evidence that an inactivated vaccine platform of chimeric influenza/RSV virus can be developed into a safe RSV vaccine candidate without priming RSV-specific T cells and immunopathology. Respiratory syncytial virus (RSV) is a major cause of respiratory tract illness and morbidity in children. Hence, there is a need to develop an effective vaccine against this virus. In this article, the authors engineered chimeric influenza virus to express RSV neutralizing epitopes. The positive findings in in-vivo experiments provide a beginning for future clinical trials and perhaps eventual product realization. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Use of metaphylactic protocols based on the risk to develop bovine respiratory diseases in feedlot cattle

    Directory of Open Access Journals (Sweden)

    Layane Queiroz Magalhães

    Full Text Available ABSTRACT: Bovine respiratory diseases (BRD affect production rates negatively because it compromise health and well-being of the affected animal. The hypothesis of this study was that the use of metaphylactic protocols based on the risk to develop BRD would reduce morbidity and pulmonary lesions. For this purpose, the aims of this study were to evaluate the effect of two metaphylactic protocols on the morbidity of feedlot cattle with a known sanitary history, occurrence of pulmonary lesions at slaughter, and the possible participation of Mannheimia haemolytica, Histophilus somni, Bovine alphaherpesvirus 1 (BoHV-1 and bovine respiratory syncytial virus (BRSV in the development of BRD. An experimental study was designed in which 3,094 adult, male, cattle, were grouped according to the risk to develop BRD: a group without metaphylaxis (n=2,104, low-risk animals; b metaphylaxis group with oxytetracycline (n=789, moderate-risk animals; c metaphylaxis group with tildipirosin (n=201, high-risk animals. All cattle were immunized against pathogens associated with BRD (BoHV-1, BVDV, BRSV, PI3. The morbidity for BRD was 8.2% (253/3,094; cattle within the moderate-risk group for BRD had the lowest frequency (6.1%, followed by high-risk animals with tildipirosin metaphylaxis (6.5% and low-risk without metaphylaxis (9.1% (P=0.019. At the abattoir, 1.2% of lungs with lesions were found. There was a difference (P=0.036 in the frequency of pulmonary lesions between healthy animals (1.1% and those diagnosed with BRD (2.8%. Two agents associated with BRD were identified by PCR assays in the lungs (n=37 of cattle: M. haemolytica (16.2% and H. somni (5.4%. In addition, concomitant infections involving these pathogens were identified in the lungs of two steers. These results demonstrate that the use of metaphylactic protocols, based on the risk to develop BRD, reduces morbidity and pulmonary lesions in affected cattle. Furthermore, pulmonary lesions were more

  7. Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to 1995 and 1998

    Directory of Open Access Journals (Sweden)

    Straliotto Selir M

    2001-01-01

    Full Text Available We analyzed the respiratory syncytial virus (RSV groups and their epidemiological pattern that were detected over the course of seven years in southern Brazil. The two RSV groups co-circulated each year, but frequencies of groups A and B varied both between and within yearly outbreaks. In 1991, group A predominated over group B (p=0.0016. RSV outbreaks analyzed showed a temperature-dependent pattern and no association with rainfall, similarly to other countries from southern South America. Knowledge of the variants is important in terms of both diagnosis and definition of a vaccine composition.

  8. Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants.

    Science.gov (United States)

    McLaurin, K K; Farr, A M; Wade, S W; Diakun, D R; Stewart, D L

    2016-11-01

    Infection with respiratory syncytial virus (RSV), which causes lower respiratory tract infections, is the leading cause of hospitalization among children preterm and full-term infants without chronic lung disease or other high-risk conditions. This analysis used Truven Health Market Scan Multi-State Medicaid and Commercial Claims and Encounters databases, which contain a combined 4 million births from 2003 to 2013. Infants with comorbid conditions associated with increased risk for RSV infection were excluded. Infants were classified as preterm (position. Costs of RSV hospitalizations were captured and reported in 2014 USD. Inpatient claims for RSV hospitalizations were evaluated for the presence of codes indicating admission to the intensive care unit (ICU), use of mechanical ventilation (MV) and length of stay. These three measures were used to describe hospital severity. Chronologic age at the time of RSV hospitalization was also captured. Data were summarized and no statistical comparisons were conducted. There were 1 683 188 infants insured through Medicaid and 1 663 832 infants insured through commercial plans born from 1 July 2003 to 30 June 2013. Of those, 10.8 and 8.8% in each database, respectively, were born prematurely. There were 29 967 Medicaid-insured infants and 16 310 commercially insured infants with an RSV hospitalization during their first year of life. Mean first-year RSV hospitalization costs were higher for preterm infants, ranging from $8324 and $10 570 for full-term infants to $15 839 and $19 931 for preterm infants 33-34 wGA, and to $39 354 and $40 813 for preterm infants preterm infants, with longer lengths of stay, a higher proportion of infants admitted to the intensive care unit (ICU) and increased use of MV compared with full-term infants. Mean costs of RSV hospitalizations with a PICU admission ranged from approximately $35 000 to $89 000. In both Medicaid and commercial groups, costs were greater for

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

    Science.gov (United States)

    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

  10. Sequencing and Analysis of Globally Obtained Human Respiratory Syncytial Virus A and B Genomes

    Science.gov (United States)

    Bose, Michael E.; He, Jie; Shrivastava, Susmita; Nelson, Martha I.; Bera, Jayati; Halpin, Rebecca A.; Town, Christopher D.; Lorenzi, Hernan A.; Noyola, Daniel E.; Falcone, Valeria; Gerna, Giuseppe; De Beenhouwer, Hans; Videla, Cristina; Kok, Tuckweng; Venter, Marietjie; Williams, John V.; Henrickson, Kelly J.

    2015-01-01

    Background Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. Partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for RSV. The goal of our study was to sequence the genomes of RSV strains collected from multiple countries to further understand the global diversity of RSV at a whole-genome level. Methods We collected RSV samples and isolates from Mexico, Argentina, Belgium, Italy, Germany, Australia, South Africa, and the USA from the years 1998-2010. Both Sanger and next-generation sequencing with the Illumina and 454 platforms were used to sequence the whole genomes of RSV A and B. Phylogenetic analyses were performed using the Bayesian and maximum likelihood methods of phylogenetic inference. Results We sequenced the genomes of 34 RSVA and 23 RSVB viruses. Phylogenetic analysis showed that the RSVA genome evolves at an estimated rate of 6.72 × 10-4 substitutions/site/year (95% HPD 5.61 × 10-4 to 7.6 × 10-4) and for RSVB the evolutionary rate was 7.69 × 10-4 substitutions/site/year (95% HPD 6.81 × 10-4 to 8.62 × 10-4). We found multiple clades co-circulating globally for both RSV A and B. The predominant clades were GA2 and GA5 for RSVA and BA for RSVB. Conclusions Our analyses showed that RSV circulates on a global scale with the same predominant clades of viruses being found in countries around the world. However, the distribution of clades can change rapidly as new strains emerge. We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized. PMID:25793751

  11. Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

  12. Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in Vero cells.

    Science.gov (United States)

    Derscheid, Rachel J; van Geelen, Albert; McGill, Jodi L; Gallup, Jack M; Cihlar, Tomas; Sacco, Randy E; Ackermann, Mark R

    2013-11-22

    Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.

  13. Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells

    Directory of Open Access Journals (Sweden)

    Rachel J. Derscheid

    2013-11-01

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37 strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.

  14. Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus.

    Science.gov (United States)

    Mitra, Namita; Cernicchiaro, Natalia; Torres, Siddartha; Li, Feng; Hause, Ben M

    2016-08-01

    Bovine respiratory disease (BRD) is the most costly disease affecting the cattle industry. The pathogenesis of BRD is complex and includes contributions from microbial pathogens as well as host, environmental and animal management factors. In this study, we utilized viral metagenomic sequencing to explore the virome of nasal swab samples obtained from feedlot cattle with acute BRD and asymptomatic pen-mates at six and four feedlots in Mexico and the USA, respectively, in April-October 2015. Twenty-one viruses were detected, with bovine rhinitis A (52.7 %) and B (23.7 %) virus, and bovine coronavirus (24.7 %) being the most commonly identified. The emerging influenza D virus (IDV) tended to be significantly associated (P=0.134; odds ratio=2.94) with disease, whereas viruses commonly associated with BRD such as bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus and bovine parainfluenza 3 virus were detected less frequently. The detection of IDV was further confirmed using a real-time PCR assay. Nasal swabs from symptomatic animals had significantly more IDV RNA than those collected from healthy animals (P=0.04). In addition to known viruses, new genotypes of bovine rhinitis B virus and enterovirus E were identified and a newly proposed species of bocaparvovirus, Ungulate bocaparvovirus 6, was characterized. Ungulate tetraparvovirus 1 was also detected for the first time in North America to our knowledge. These results illustrate the complexity of the virome associated with BRD and highlight the need for further research into the contribution of other viruses to BRD pathogenesis.

  15. Low Retinol-Binding Protein and Vitamin D Levels Are Associated with Severe Outcomes in Children Hospitalized with Lower Respiratory Tract Infection and Respiratory Syncytial Virus or Human Metapneumovirus Detection.

    Science.gov (United States)

    Hurwitz, Julia L; Jones, Bart G; Penkert, Rhiannon R; Gansebom, Shane; Sun, Yilun; Tang, Li; Bramley, Anna M; Jain, Seema; McCullers, Jonathan A; Arnold, Sandra R

    2017-08-01

    Retinol binding protein and vitamin D were measured in children aged respiratory tract infection and respiratory syncytial virus and/or human metapneumovirus detections. Low vitamin levels were observed in 50% of the children and were associated with significantly elevated risk of the need for intensive care unit admission and invasive mechanical ventilation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Short communication. Prevalence of antibodies against Parainfluenza virus type 3, Respiratory syncitial virus and bovine Herpesvirus type 1 in sheep from Northern Prefectures of Japan

    Directory of Open Access Journals (Sweden)

    Massimo Giangaspero

    2013-09-01

    Full Text Available Ovine sera collected in the Prefectures of Hokkaido, Aomori and Iwate in the Northern Japan were examined for the presence of antibodies against Respiratory syncytial virus (RSV, bovine Herpesvirus type 1 (infectious bovine rhinotracheitis: IBR and Parainfluenza virus type 3 (PIV3 using serum neutralisation (SN and enzyme-linked immunosorbent assay (ELISA tests. Twenty-three animals (11.73% out of the 196 tested were sero-positive to PIV3. Sixteen animals (8.69% out of the 184 tested reacted to RSV. No animals were positive to IBR antigen. Sero-conversions to PIV3 were detected in Hokkaido and Iwate (14.92% and 8.82%, respectively. Antibodies against RSV were detected in Hokkaido (9.23% and Aomori (14.28%. Although no diagnostic measures were in place, the infections did not appear to be related to any reduction in sheep productivity.

  17. Prevalence of antibodies against Parainfluenza virus type 3, Respiratory syncitial virus and bovine Herpesvirus type 1 in sheep from Northern Prefectures of Japan.

    Science.gov (United States)

    Giangaspero, Massimo; Savini, Giovanni; Orusa, Riccardo; Osawa, Takeshi; Harasawa, Ryô

    2013-01-01

    Ovine sera collected in the Prefectures of Hokkaido, Aomori and Iwate in the Northern Japan were examined for the presence of antibodies against Respiratory syncytial virus (RSV), bovine Herpesvirus type 1 (infectious bovine rhinotracheitis: IBR) and Parainfluenza virus type 3 (PIV3) using serum neutralisation (SN) and enzyme-linked immunosorbent assay (ELISA) tests. Twenty-three animals (11.73%) out of the 196 tested were sero-positive to PIV3. Sixteen animals (8.69%) out of the 184 tested reacted to RSV. No animals were positive to IBR antigen. Sero-conversions to PIV3 were detected in Hokkaido and Iwate (14.92% and 8.82%, respectively). Antibodies against RSV were detected in Hokkaido (9.23%) and Aomori (14.28%). Although no diagnostic measures were in place, the infections did not appear to be related to any reduction in sheep productivity.

  18. Clinical characteristics of respiratory syncytial virus infection in neonates and young infants

    Directory of Open Access Journals (Sweden)

    Savić Nataša

    2011-01-01

    Full Text Available Introduction/Aim. Infection with respiratory syncytial virus (RSV occurs during the first year of life in 50% of children and 20%-40% of them have signs of lower respiratory tract infection (bronchiolitis or pneumonia. There is an increased risk for complicated course and death from RSV infection in premature infants, especially those with bronchopulmonary dysplasia (BPD or congenital heart disease. The aim of our study was to analyze clinical characteristics of laboratory confirmed RSV infection in order to evaluate the need for preventive measures in neonates and young infants. Methods. The prospective study included children under age of 12 months admitted to our hospital in the period November 2008-March 2009 who were positive for RSV by enzyme immunoassay membrane test. The course of disease was assessed by clinical score and radiographic findings. Results. Infection with RSV was confirmed in 91 patients: 21 (23.0% were under the age of 30 days, 37 (40.7% were between 31-60 days, and 33 patients (36.3% were older than 60 days (p > 0.05. The highest hospitalization rate was in January - 33 patients (36.3%; p < 0.01. Disease severity score in these age groups (AG were: 8.4 ± 0.4 (AG 0-30 days; 9.0 ± 0.3 (AG 31-60 days and 8.3 ± 0.3 (AG > 60 days, without statistically significant difference among the groups (p > 0.05. Clinical scores in patients with and without risk factors were 10.5 ± 0.5 and 8.3 ± 0.2, respectively (p < 0.01. Pathological radiographic findings were observed in 72 (79.1% and complications (apnea, significant atelectasis, encephalopathy occured in 15 (16.5% patients. The average length of hospital stay in complicated and uncomplicated course of the disease was 9 days and 6 days, respectively (p < 0.01. Therapy in 85 (93.4% patients included bronchodilators, while systemic glucocorticoids and oxygen therapy were used in 51 (56.0% and 44 (48.4% patients, respectively. Death occured in 2 (2.2% patients, both from a high

  19. Unravelling respiratory syncytial virus outbreaks in Buenos Aires, Argentina: Molecular basis of the spatio-temporal transmission.

    Science.gov (United States)

    Rojo, Gabriel Lihue; Goya, Stephanie; Orellana, Mariana; Sancilio, Andrea; Rodriguez Perez, Alberto; Montali, César; García, Carolina; Sosa, Lilian; Musto, Alejandra; Alvarez, Daniela; Castello, Alejandro; Viegas, Mariana

    2017-08-01

    Respiratory syncytial virus (RSV) is the main viral cause of hospitalization due to acute lower respiratory tract infections in infants worldwide. Several vaccines against RSV are under research and development, which are about to be approved. We evaluated transmission patterns in different settings to determine age-specific vaccination targets from a viral perspective. We sequenced the G glycoprotein's ectodomain of a constant clinical sampling between two epidemic outbreaks in a limited geographical region and performed phylogeographic analyses. We described a spatio-temporal transmission between local strains, which were originated in the center of the analyzed area and then spread to others. Interestingly, that central area reported the highest population density of the region and also showed overcrowding. This information should be considered by public health systems to evaluate vaccination at all ages in those areas to decrease viral transmission and in lower density populations only susceptible children should be vaccinated. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy.

    Science.gov (United States)

    Bradley, Joseph P; Bacharier, Leonard B; Bonfiglio, JoAnn; Schechtman, Kenneth B; Strunk, Robert; Storch, Gregory; Castro, Mario

    2005-01-01

    Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children. We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O(2) saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy. We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 +/- 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O(2) saturation: 91.6 +/- 7.3%; length of stay: 2.5 +/- 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung. Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O(2)) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O(2) saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine

  1. Respiratory syncytial virus hospitalization trends in infants with chronic lung disease of infancy, 1998–2008

    Directory of Open Access Journals (Sweden)

    Groothuis JR

    2011-09-01

    Full Text Available Jessie R Groothuis1, Jon P Fryzek1,2, Doris Makari1, Duane Steffey2, William J Martone11MedImmune, LLC, Gaithersburg, MD, 2Exponent, Menlo Park, CA, USAObjective: Infants with chronic lung disease of infancy (CLDI are at high risk for severe respiratory syncytial virus (RSV illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged <2 years between 1998 and 2008 in the USA to determine trends in rates of hospitalizations due to RSV (RSVH since the launch of palivizumab.Materials and methods: Data from the United States National Hospital Discharge Survey, a multistage systematic survey sample of US hospitals, were assembled. We defined RSVH using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM codes of 079.6 (RSV, 466.11 (acute bronchiolitis due to RSV, and 480.1 (pneumonia due to RSV. Quarterly rates of RSVH were assessed for children with CLDI (ICD-9-CM code 770.7 and calculated between 1998 and 2008. Because RSV may be miscoded, the analysis was repeated after expanding the definition of RSVH to include all acute bronchitis and acute bronchiolitis (ABH (ICD-9-CM = 466. Trends were described using linear regression with seasonal indicators included in the model.Results: On average, about 966 RSVH (range 98–1373 RSVH per year were found for children <2 years with CLDI in the USA between 1998 and 2008. Over the 11-year period, the predicted rate of RSVH statistically significantly decreased by 48% (from 93.78 to 49.06 RSVH per 1 million children (P = 0.013. Addition of ABH resulted in a nonstatisically significant decrease of 32% over the 10-year period (P = 0.102.Conclusion: These results suggest that there has been a decrease in the rate of RSVH in infants with CLDI between 1998 and 2008. The reasons for this decrease

  2. Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses.

    Science.gov (United States)

    Palomo, Concepción; Mas, Vicente; Thom, Michelle; Vázquez, Mónica; Cano, Olga; Terrón, María C; Luque, Daniel; Taylor, Geraldine; Melero, José A

    2016-06-01

    Human respiratory syncytial virus (hRSV) vaccine development has received new impetus from structure-based studies of its main protective antigen, the fusion (F) glycoprotein. Three soluble forms of F have been described: monomeric, trimeric prefusion, and trimeric postfusion. Most human neutralizing antibodies recognize epitopes found exclusively in prefusion F. Although prefusion F induces higher levels of neutralizing antibodies than does postfusion F, postfusion F can also induce protection against virus challenge in animals. However, the immunogenicity and protective efficacy of the three forms of F have not hitherto been directly compared. Hence, BALB/c mice were immunized with a single dose of the three proteins adjuvanted with CpG and challenged 4 weeks later with virus. Serum antibodies, lung virus titers, weight loss, and pulmonary pathology were evaluated after challenge. Whereas small amounts of postfusion F were sufficient to protect mice, larger amounts of monomeric and prefusion F proteins were required for protection. However, postfusion and monomeric F proteins were associated with more pathology after challenge than was prefusion F. Antibodies induced by all doses of prefusion F, in contrast to other F protein forms, reacted predominantly with the prefusion F conformation. At high doses, prefusion F also induced the highest titers of neutralizing antibodies, and all mice were protected, yet at low doses of the immunogen, these antibodies neutralized virus poorly, and mice were not protected. These findings should be considered when developing new hRSV vaccine candidates. Protection against hRSV infection is afforded mainly by neutralizing antibodies, which recognize mostly epitopes found exclusively in the viral fusion (F) glycoprotein trimer, folded in its prefusion conformation, i.e., before activation for membrane fusion. Although prefusion F is able to induce high levels of neutralizing antibodies, highly stable postfusion F (found after

  3. Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Soukup, J.; Koren, H.S.; Becker, S. (TRC Alliance Inc., Chapel Hill, NC (United States))

    1993-02-01

    This 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) 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. Statistical analysis of the O3 effect on AM cytokine production induced by the different multiplicities, however, revealed no significant effect of O3. Based on these observations it appears unlikely that O3 alters susceptibility of AM to infection with RSV, nor does O3 dramatically alter cytokine production in response to RSV since effects on IL-1 and IL-6 secretion were only found with the lowest levels of infection which induced cytokine release.

  4. [Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso].

    Science.gov (United States)

    Ouédraogo Yugbaré, S O; Ouédraogo, R; Nenebi, A; Traoré, B; Congo, L; Yonli, F; Kima, D; Bonané, P; Yé, D; Plantier, J-C; Vabret, A; Marguet, C; Gueudin, M

    2016-02-01

    Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

  5. Estimates of influenza and respiratory syncytial virus incidences with fraction modeling approach in Baguio City, the Philippines, 2012-2014.

    Science.gov (United States)

    Kamigaki, Taro; Aldey, Portia P; Mercado, Edelwisa S; Tan, Alvin G; Javier, Jenaline B; Lupisan, Socorro P; Oshitani, Hitoshi; Tallo, Veronica L

    2017-07-01

    Estimation of the incidences of influenza and respiratory syncytial virus (RSV) infection is important for disease control. Previous estimate in the city showed a substantial burden of influenza in both outpatients and inpatients while it did not account for individuals who do not seek medical attention nor RSV. A total of 17 674 influenza-like illness (ILI) and 13 242 severe acute respiratory illness (SARI) cases were recruited, and samples were collected from 6267 and 2962 of ILI and SARI cases, respectively. RT-PCR assays were performed to detect influenza and RSV in the samples. A health-seeking behavior survey was conducted from February 2014 to April 2014 to estimate the fraction of infected individuals who did not seek medical attention between rainy and dry season. Average influenza and RSV incidence rates in outpatients were 1.6 and 1.4 per 1000 individuals, respectively, and the highest incidence rate for both viruses was found in the of 6-23 month age group. Average influenza and RSV hospitalization incidence rates were 1.7 and 1.9 per 1000 individuals, respectively. Further, we estimated that the incidence rates of influenza and RSV in individuals who did not seek medical attention were threefold and 1.6-fold those in the medically attended population. Respiratory syncytial virus and influenza pose a substantial disease burden, particularly in hospitalized cases. The implementation of either a community-based approach or an enhanced surveillance system in combination with a community survey will allow a better understanding of the disease burdens of RSV and influenza in the Philippines. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  6. Monitoring epidemic viral respiratory infections using one-step real-time triplex RT-PCR targeting influenza A and B viruses and respiratory syncytial virus.

    Science.gov (United States)

    Papillard-Marechal, Solesne; Enouf, Vincent; Schnuriger, Aurélie; Vabret, Astrid; Macheras, Edouard; Rameix-Welti, Marie-Anne; Page, Bernard; Freymuth, François; van der Werf, Sylvie; Garbarg-Chenon, Antoine; Chevallier, Bertrand; Gaillard, Jean-Louis; Gault, Elyanne

    2011-04-01

    Rapid and specific diagnosis of influenza A/B and respiratory syncytial virus (RSV) viruses is needed for optimal management of patients with acute respiratory infections. In this study, a one-step triplex real-time RT-PCR assay was developed for rapid diagnosis of influenza A/B and RSV infections to optimize diagnosis efficiency of acute respiratory infections. Cell-culture supernatants and clinical samples were used to evaluate specificity and sensitivity of the assay. The assay was used routinely during two winter epidemics for testing respiratory specimens from 2,417 patients. The limit of detection in cell-culture supernatant was 1-10 plaque forming units/input (influenza A/B) and 2 × 10(-2) 50% tissue culture infectious dose/input (RSV). In clinical samples, the assay was as sensitive as commercial molecular assays for the detection of each influenza A/B and RSV (Flu-A/B and RSV-A/B r-gene™) individually, and far more sensitive than antigen detection. During the winter 2008-2009, the assay identified 145 RSV, 42 influenza A, and one mixed RSV-influenza A infections among 298 patients. The next winter, the assay was used in two independent hospital laboratory settings. 776 patients were tested in one hospital and 1,343 in the other, resulting in 184 and 501 RSV, 133 and 150 influenza A, and 1 and 11 mixed RSV-influenza A infections, respectively, being detected. This new user-friendly assay allows rapid (within hours), effective molecular diagnosis of single or mixed infections involving influenza A (including seasonal A H1N1 and H3N2, and A(H1N1) 2009), influenza B, and RSV(A/B). The assay is very valuable for managing patients during winter epidemics when influenza and respiratory syncytial viruses co-circulate. Copyright © 2011 Wiley-Liss, Inc.

  7. Water extract of Cinnamomum cassia Blume inhibited human respiratory syncytial virus by preventing viral attachment, internalization, and syncytium formation.

    Science.gov (United States)

    Yeh, Chia Feng; Chang, Jung San; Wang, Kuo Chih; Shieh, Den En; Chiang, Lien Chai

    2013-05-20

    Cinnamomum cassia Blume is a popular traditional Chinese herbal medicine that has been used to manage respiratory tract disease, including common cold and chronic bronchitis for thousand years. Human respiratory syncytial virus (HRSV) is one of the leading causes of severe lower respiratory tract illness worldwide. No effective therapeutic modality against HRSV infection has been proved. It is unknown whether Cinnamomum cassia is effective against HRSV. This study tested the hypothesis that Cinnamomum cassia can effectively decrease HRSV-induced plaque formation and syncytium formation in respiratory mucosal cell lines. Antiviral activity of the hot water extract of Cinnamomum cassia against HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Its ability to inhibit the synthesis of viral fusion (F) protein was examined by Western blot assay. Cinnamomum cassia dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (pCinnamomum cassia was more effective when given before viral infection (pCinnamomum cassia could inhibit F protein production and syncytium formation to interfere with HRSV spreading. Cinnamomum cassia prevented airway epithelia from HRSV infection through inhibiting viral attachment, internalization and syncytium formation. Cinnamomum cassia could be a candidate to develop therapeutic modalities to manage HRSV infection in the future. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Respiratory syncytial virus infection is associated with an altered innate immunity and a heightened pro-inflammatory response in the lungs of preterm lambs.

    Science.gov (United States)

    Sow, Fatoumata B; Gallup, Jack M; Krishnan, Subramaniam; Patera, Andriani C; Suzich, Joann; Ackermann, Mark R

    2011-08-09

    Factors explaining the greater susceptibility of preterm infants to severe lower respiratory infections with respiratory syncytial virus (RSV) remain poorly understood. Fetal/newborn lambs are increasingly appreciated as a model to study key elements of RSV infection in newborn infants due to similarities in lung alveolar development, immune response, and susceptibility to RSV. Previously, our laboratory demonstrated that preterm lambs had elevated viral antigen and developed more severe lesions compared to full-term lambs at seven days post-infection. Here, we compared the pathogenesis and immunological response to RSV infection in lungs of preterm and full-term lambs. Lambs were delivered preterm by Caesarian section or full-term by natural birth, then inoculated with bovine RSV (bRSV) via the intratracheal route. Seven days post-infection, lungs were collected for evaluation of cytokine production, histopathology and cellular infiltration. Compared to full-term lambs, lungs of preterm lambs had a heightened pro-inflammatory response after infection, with significantly increased MCP-1, MIP-1α, IFN-γ, TNF-α and PD-L1 mRNA. RSV infection in the preterm lung was characterized by increased epithelial thickening and periodic acid-Schiff staining, indicative of glycogen retention. Nitric oxide levels were decreased in lungs of infected preterm lambs compared to full-term lambs, indicating alternative macrophage activation. Although infection induced significant neutrophil recruitment into the lungs of preterm lambs, neutrophils produced less myeloperoxidase than those of full-term lambs, suggesting decreased functional activation. Taken together, our data suggest that increased RSV load and inadequate immune response may contribute to the enhanced disease severity observed in the lungs of preterm lambs.

  9. Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

    NARCIS (Netherlands)

    Habibi, Maximillian S; Jozwik, Agnieszka; Makris, Spyridon; Dunning, Jake; Paras, Allan; DeVincenzo, John P; de Haan, Cornelis A M; Wrammert, Jens; Openshaw, Peter J M; Chiu, Christopher

    2015-01-01

    RATIONALE: Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of

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

    NARCIS (Netherlands)

    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|info:eu-repo/dai/nl/313979707; Bont, LJ|info:eu-repo/dai/nl/304813370; Paes, Bosco

    2016-01-01

    BACKGROUND: In several countries RSV 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 gestational age

  11. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Preterm Infants Without Chronic Lung Disease or Congenital Heart Disease

    NARCIS (Netherlands)

    Figueras-Aloy, Josep; Manzoni, Paolo; Paes, Bosco; Simões, Eric A F; Bont, Louis; Checchia, Paul A; Fauroux, Brigitte; Carbonell-Estrany, Xavier

    2016-01-01

    INTRODUCTION: The REGAL (RSV Evidence-a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This second publication covers the risk and burden of RSV

  12. Population based external validation of a European predictive model for respiratory syncytial virus hospitalization of premature infants born 33 to 35 weeks of gestational age

    DEFF Research Database (Denmark)

    Stensballe, Lone G; Fullarton, John R; Carbonell-Estrany, Xavier

    2010-01-01

    Prospectively collected population-based data on 2529 Danish infants born at 33 to 35 weeks of gestation were used to validate an European predictive model of respiratory syncytial virus (RSV) hospitalization. The model was found to be robust with a diagnostic accuracy of 65.9% to distinguish...

  13. Persistence of airway hyperresponsiveness and viral antigen following respiratory syncytial virus bronchiolitis in young guinea-pigs.

    Science.gov (United States)

    Riedel, F; Oberdieck, B; Streckert, H J; Philippou, S; Krusat, T; Marek, W

    1997-03-01

    Respiratory syncytial virus (RSV) bronchiolitis in infancy is known to be followed by chronic respiratory symptoms and airway hyperresponsiveness in a subgroup of patients. To further investigate the pathogenesis of RSV-induced chronic airway pathology, we infected young guinea-pigs at 4 weeks of age with RSV applied as an aerosol (n=30), and control guinea-pigs with virus-free culture medium (n=24). Infection was confirmed by positive antibody titre to RSV after 6 weeks, and by typical pathological changes of bronchiolitis after 1 week in six animals from each group. Airway hyperresponsiveness was measured weekly for 5 weeks by histamine challenge, using body-plethysmographic measurement of compressed air (CA). The provocative concentration of histamine producing significant airway obstruction (i.e. CA = 0.1 mL) (PC0.1 mL CA in mg x mL(-1)) was calculated from dose-response curves. Six weeks postinfection, the lungs were investigated for the presence of inflammation and of viral antigen by immunofluorescence and immunohistochemistry using a rabbit hyperimmune serum and monoclonal antibodies. Airway responsiveness was increased in the RSV group 1 week postinfection compared to the control group (PC0.1 mL CA median 2.50 vs >10 mg x mL(-1); p10 mg x mL(-1); p<0.001). During the same period, viral antigen persisted in the lungs of infected animals, although there was less inflammation at 6 weeks postinfection than at 1 week postinfection. In guinea-pigs, respiratory syncytial virus infection of the airways causes persistent airway hyperresponsiveness over a period of at least 5 weeks. During this time, viral antigen, but not inflammation, remains detectable in the lungs and might be responsible for ongoing airway hyperresponsiveness.

  14. Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

    OpenAIRE

    Miller, Allison L.; Sims, Gary P.; Brewah, Yambasu A.; Rebelatto, Marlon C.; Kearley, Jennifer; Benjamin, Ebony; Keller, Ashley E.; Brohawn, Philip; Herbst, Ronald; Coyle, Anthony J.; Humbles, Alison A.; Kolbeck, Roland

    2012-01-01

    Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/− ) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflam...

  15. Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.

    Science.gov (United States)

    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 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 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 young children from developing countries.

  16. Rapid detection of respiratory syncytial virus in nasopharyngeal aspirates by reverse transcription and polymerase chain reaction amplification.

    Science.gov (United States)

    Paton, A W; Paton, J C; Lawrence, A J; Goldwater, P N; Harris, R J

    1992-01-01

    A rapid method for detection of respiratory syncytial virus (RSV) in nasopharyngeal aspirates, involving a combination of reverse transcription and polymerase chain reaction amplification (RT-PCR), has been developed. The RT-PCR assay employs oligonucleotide primers specific for the region of the RSV genome which encodes the F1 subunit of the fusion (F) glycoprotein. Other respiratory viruses do not give a positive reaction. The RT-PCR assay was tested on 202 nasopharyngeal aspirates collected from children with clinical signs of respiratory infection, and the results from RT-PCR were compared with those obtained from virus culture and direct detection by enzyme immunoassay (EIA). RT-PCR results were positive in 118 of 125 samples from which RSV was cultured, as well as in 4 of 7 samples which were culture negative but EIA positive. RT-PCR results were negative in 68 of 70 culture-negative, EIA-negative samples, which included 11 samples from which other respiratory viruses were isolated. The speed, sensitivity (94.6%), and specificity (greater than 97%) of the RT-PCR assay suggest that this technique could be useful for rapid detection of RSV in clinical samples. Images PMID:1374080

  17. Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months.

    Directory of Open Access Journals (Sweden)

    Angela Mary Fonceca

    Full Text Available Human respiratory syncytial virus (RSV remains the most common cause of severe lower respiratory tract disease amongst infants, and continues to cause annual epidemics of respiratory disease every winter worldwide. Demonstrating placental transmission of viable RSV in human samples is a major paradigm shift in respiratory routes considered likely for RSV transmission.Droplet digital PCR (ddPCR was used to identify RSV present in cord blood mononucleocytes (CBM. CBMs testing positive for RSV were treated with phytohemagglutinin (PHA, PHA and nitric oxide (NO or PHA, NO and palivizumab, and co-cultured with HeLa cell monolayers. Subsequent immuno-staining for RSV was used to visualize infective viral plaques.RSV was detected in 26 of 45 samples (57.7% by ddPCR. CBM's collected in winter were more likely to test positive for RSV (17/21 samples, risk = 80%, OR = 7.08; 95% CI 1.80-27.80; p = 0.005 compared to non-winter months (9/24 samples, 37.5%. RSV plaques were observed in non-treated and treated co-cultured HeLa monolayers.Demonstrating active RSV in CBMs suggests in utero transmission of infective virus to the fetus without causing overt disease. This is likely to have an important impact on immune development as well as future virus-host interactions, thereby warranting further investigation.

  18. Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months.

    Science.gov (United States)

    Fonceca, Angela Mary; Chopra, Abha; Levy, Avram; Noakes, Paul Stanton; Poh, Matthew Wee-Peng; Bear, Natasha Leanne; Prescott, Susan; Everard, Mark Lloyd

    2017-01-01

    Human respiratory syncytial virus (RSV) remains the most common cause of severe lower respiratory tract disease amongst infants, and continues to cause annual epidemics of respiratory disease every winter worldwide. Demonstrating placental transmission of viable RSV in human samples is a major paradigm shift in respiratory routes considered likely for RSV transmission. Droplet digital PCR (ddPCR) was used to identify RSV present in cord blood mononucleocytes (CBM). CBMs testing positive for RSV were treated with phytohemagglutinin (PHA), PHA and nitric oxide (NO) or PHA, NO and palivizumab, and co-cultured with HeLa cell monolayers. Subsequent immuno-staining for RSV was used to visualize infective viral plaques. RSV was detected in 26 of 45 samples (57.7%) by ddPCR. CBM's collected in winter were more likely to test positive for RSV (17/21 samples, risk = 80%, OR = 7.08; 95% CI 1.80-27.80; p = 0.005) compared to non-winter months (9/24 samples, 37.5%). RSV plaques were observed in non-treated and treated co-cultured HeLa monolayers. Demonstrating active RSV in CBMs suggests in utero transmission of infective virus to the fetus without causing overt disease. This is likely to have an important impact on immune development as well as future virus-host interactions, thereby warranting further investigation.

  19. Brazilian strain of bovine respiratory coronavirus is derived from dual enteric and respiratory tropism.

    Science.gov (United States)

    Beuttemmuller, E A; Alfieri, A F; Headley, S A; Alfieri, A A

    2017-04-05

    Bovine coronavirus (BCoV) is a pathogen related to enteric and respiratory diseases in cattle worldwide. Enteric (BECoV) strains of BCoV are predominant in South America, and genetic investigations have been conducted to identify its relationship with isolates of respiratory origin (BRCoV). In this study, we used a BRCoV strain (BR-UEL11) derived from an outbreak of respiratory disease in feedlot cattle in southern Brazil, and compared the partial sequence of the polymorphic region of Spike (which was detected and sequenced by two distinct reverse transcription-polymerase chain reactions) with those of other BCoV strains. The phylogenetic relationship of BR-UEL11 with Brazilian BCoV, which is associated with calf diarrhea and winter dysentery (enteric, BECoV; respiratory, BRCoV), and classical reference prototypes was analyzed. The analysis showed that the BRCoV strains from Brazil clustered with a clade that was distinct from most isolates associated with calf diarrhea (BECoV) and ancestral prototype strains such as Mebus, Nebraska, and LYVB. Furthermore, the BRCoV strains from Brazil clustered with a clade that contained recent strains associated with winter dysentery, showing 98-99% nucleotide identity with those strains. These results suggested that the Brazilian BCoV evolved from being solely enteric to a dual enteric and respiratory tropic virus.

  20. Prevention of respiratory syncytial virus infections Prevenção das infecções pelo vírus sincicial respiratório

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2001-06-01

    Full Text Available Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia, and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.Em todo o mundo, o vírus sincicial respiratório é o principal agente de infecções agudas das vias aéreas baixas em lactentes jovens e crianças. Aos dois anos de idade, praticamente todas as crianças já foram infectadas, e as reinfeções são comuns

  1. Lower number of plasmacytoid dendritic cells in peripheral blood of children with bronchiolitis following respiratory syncytial virus infection

    Science.gov (United States)

    Weng, Kaizhi; Zhang, Jiaxiang; Mei, Xuqiao; Wu, Ayang; Zhang, Baozhong; Cai, Mengyun; Zheng, Yuanhai; Ke, Zhuanye

    2014-01-01

    Objectives Dendritic cells (DCs) are key mediators of allergic airway inflammation. Thus, it is important to understand the relationship between respiratory syncytial virus (RSV) infection and DCs, especially in children with RSV bronchiolitis. Methods We collected peripheral blood from 71 children with RSV bronchiolitis at the time of admission and 28 children who were followed up 3 months following admission. Flow cytometry was performed to detect dendritic cell immunophenotypes. Results Patients with RSV bronchiolitis exhibited significantly higher number of myeloid DCs and lower number of plasmacytoid DCs at the time of admission and 3 months following discharge, compared with healthy controls. These children had a significantly higher myeloid/plasmacytoid ratio 3 months after discharge compared with healthy controls. Conclusions Among children with RSV bronchiolitis, there is an imbalance in peripheral blood myeloid/plasmacytoid ratio. The low number of plasmacytoid DCs in peripheral blood indicates the development of bronchiolitis due to RSV infection. PMID:24528606

  2. Cytologic diagnosis of respiratory syncytial virus infection in a bronchoalveolar lavage specimen from a bone marrow transplant recipient.

    Science.gov (United States)

    Parham, D M; Bozeman, P; Killian, C; Murti, G; Brenner, M; Hanif, I

    1993-05-01

    Cytologic examination of a bronchoalveolar lavage specimen from a 6-year-old bone marrow transplant recipient revealed pulmonary infiltrates and occasional cells containing discrete pink cytoplasmic inclusions on a May-Grunwald-Giemsa stain. Direct immunofluorescence stains of cytospins prepared from the same specimen were positive for respiratory syncytial virus (RSV). Electron microscopy revealed occasional epithelial cells with cytoplasmic inclusions composed of filamentous virions. The patient died 6 months after the specimen was taken. An autopsy showed ongoing bronchiolitis with diffuse alveolar damage. Occasional bronchiolar epithelial cells contained discrete eosinophilic cytoplasmic inclusions, which on ultrastructural examination proved to be compatible with RSV. Examination of bronchoalveolar lavage fluid from bone marrow transplant recipients should include a search for cytopathic changes compatible with RSV infection. Electron microscopy can be helpful in confirming this diagnosis.

  3. Agonistic 4-1BB antibody fails to reduce disease burden during acute respiratory syncytial virus (RSV) infection.

    Science.gov (United States)

    Norris, M J; Duan, W; Cen, Y; Moraes, T J

    2016-01-01

    Respiratory Syncytial Virus (RSV) remains a leading cause of infant morbidity and mortality worldwide. Despite this, there are limited therapeutic options. CD8 T cells have an integral role in controlling viral infections; strategies to enhance these responses may be clinically relevant. The T cell costimulatory receptor, 4-1BB, is known to play a role in expansion of antiviral CD8 T cells. In this study, we examined the effect of agonistic 4-1BB antibody at the time of RSV infection in mice. We show that this antibody did not improve outcomes in the setting of RSV infection but rather, led to increased weight loss and a reduction in RSV specific CD8 T cells in the lung. This work suggests caution in the use of agonistic 4-1BB antibody in the setting of viral infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Seasonal variability of respiratory syncytial virus infection in the Top End of the Northern Territory (2012-2014).

    Science.gov (United States)

    Fagan, Peter; McLeod, Charlie; Baird, Robert W

    2017-01-01

    To determine the prevalence of respiratory syncytial virus (RSV) in the Top End of the Northern Territory and investigate potential drivers of seasonality including rainfall and humidex (humidity and heat index). We performed a retrospective audit of laboratory confirmed cases of RSV from January 2012 to August 2014. Demographic details including age, sex and ethnicity were examined. RSV cases were correlated with monthly rainfall and humidex. There were 272 positive isolates detected from 4305 clinical samples (positivity rate 6.3%). The majority of cases occurred in children Territory has a distinct RSV season that correlates with rainfall and humidex, which differs from Southern Australian disease patterns. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  5. Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus.

    Science.gov (United States)

    Ternette, Nicola; Tippler, Bettina; Uberla, Klaus; Grunwald, Thomas

    2007-10-10

    Respiratory syncytial virus F-protein (RSV-F) is poorly expressed from DNA expression plasmids containing the wild type RSV-F open reading frame. By codon optimization, premature polyadenylation signals were deleted and a striking enhancement of RSV-F expression levels was achieved. Therefore, the immunogenicity and efficacy of wild type DNA vaccines were compared to codon optimized expression plasmids encoding full-length RSV-F or its ectodomain. Mice were immunized twice with the different DNA vaccines followed by an RSV challenge. Only codon optimized DNA vaccines and in particular the one encoding the ectodomain of RSV-F induced substantial antibody levels and reduced viral load 13-170-fold. Thus, codon optimization enhances the immunogenicity and efficacy of RSV encoding DNA vaccines.

  6. Characterization of oligosaccharide structures on a chimeric respiratory syncytial virus protein expressed in insect cell line Sf9

    Energy Technology Data Exchange (ETDEWEB)

    Wathen, M.W.; Aeed, P.A.; Elhammer, A.P. (Upjohn Co., Kalamazoo, MI (United States))

    1991-03-19

    The oligosaccharide structures added to a chimeric protein (FG) composed of the extracellular domains of respiratory syncytial virus F and G proteins, expressed in the insect cell line Sf9, were investigated. Cells were labeled in vivo with ({sup 3}H)glucosamine and infected wit a recombinant baculovirus containing the FG gene. The secreted chimeric protein was isolated by immunoprecipitation and subjected to oligosaccharide analysis. The FG protein contains two types of O-linked oligosaccharides: GalNAc and Gal{beta}1-3GalNAc constituting 17 and 66% of the total number of structures respectively. Only one type of N-linked oligosaccharide, constituting the remaining 17% of the structures on FG, was detected: a trimannosyl core structure with a fucose residue linked {alpha}1-6 to the asparagine-linked N-acetylglucosamine.

  7. Innate and adaptive cellular phenotypes contributing to pulmonary disease in mice after respiratory syncytial virus immunization and infection.

    Science.gov (United States)

    Lee, Young-Tae; Kim, Ki-Hye; Hwang, Hye Suk; Lee, Youri; Kwon, Young-Man; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Kang, Sang-Moo

    2015-11-01

    Respiratory syncytial virus (RSV) is the major leading cause of infantile viral bronchiolitis. However, cellular phenotypes contributing to the RSV protection and vaccine-enhanced disease remain largely unknown. Upon RSV challenge, we analyzed phenotypes and cellularity in the lung of mice that were naïve, immunized with formalin inactivated RSV (FI-RSV), or re-infected with RSV. In comparison with naïve and live RSV re-infected mice, the high levels of eosinophils, neutrophils, plasmacytoid and CD11b(+) dendritic cells, and IL-4(+) CD4(+) T cells were found to be contributing to pulmonary inflammation in FI-RSV immune mice despite lung viral clearance. Alveolar macrophages appeared to play differential roles in protection and inflammation upon RSV infection of different RSV immune mice. These results suggest that multiple innate and adaptive immune components differentially contribute to RSV disease and inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  9. The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

    Directory of Open Access Journals (Sweden)

    Gerard M Murray

    Full Text Available The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99 and of cattle submitted for post-mortem examination (PME: n = 34 were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV and bovine parainfluenza-3 virus (BPIV-3. Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME. Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%. While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively, PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS, was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans.

  10. MODERN POTENTIALITIES OF IMMUNOPROPHYLAXIS OF SEVERE COURSE OF THE RESPIRATORY SYNCYTIAL VIRAL INFECTION IN CHILDREN WITH THE CONSEQUENCES OF PERINATAL PATHOLOGY

    Directory of Open Access Journals (Sweden)

    L.S. Namazova-Baranova

    2011-01-01

    Full Text Available To a risk group of a heavy course of the respiratory syncytial viral (RSV infection could be ascribed preterm infants, born before the 35th week of gestation inclusive, as well as children under 2 years old with the bronchopulmonary dysplasia or hemodynamically significant congenital heart defects. World experience shows that the seasonal immunoprophylaxis against RSV-infection with palivizumab in these patients enables to reduce the frequency of hospitalization and resuscitation measures, as well as to decrease the number of deaths. The article presents authors’ clinical and laboratory data and instrumental evaluation of the efficacy and safety of palivizumab on specific clinical examples.Key words: respiratory syncytial virus, acute respiratory viral infection, prematurity, bronchopulmonary dysplasia, congenital heart defects, palivizumab.

  11. Identification of group B respiratory syncytial viruses that lack the 60-nucleotide duplication after six consecutive epidemics of total BA dominance at coastal Kenya.

    Science.gov (United States)

    Agoti, Charles N; Gitahi, Caroline W; Medley, Graham F; Cane, Patricia A; Nokes, D James

    2013-11-01

    Respiratory syncytial virus BA genotype has reportedly replaced other group B genotypes worldwide. We report the observation of three group B viruses, all identical in G sequence but lacking the BA duplication, at a coastal district hospital in Kenya in early 2012. This follows a period of six consecutive respiratory syncytial virus (RSV) epidemics with 100% BA dominance among group B isolates. The new strains appear only distantly related to BA variants and to previously circulating SAB1 viruses last seen in the district in 2005, suggesting that they were circulating elsewhere undetected. These results are of relevance to an understanding of RSV persistence. © 2013 John Wiley & Sons Ltd. Influenza and Other Respiratory Viruses published by John Wiley & Sons.

  12. Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease.

    Science.gov (United States)

    Fulton, R W; d'Offay, J M; Landis, C; Miles, D G; Smith, R A; Saliki, J T; Ridpath, J F; Confer, A W; Neill, J D; Eberle, R; Clement, T J; Chase, C C L; Burge, L J; Payton, M E

    2016-06-24

    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 from 114 cattle on initial BRD treatment. Processing included modified live virus (MLV) vaccination. Seven BRD necropsy cases were included for 121 total cases. Mean number of days on feed before first sample was 14.9 days. Swabs and tissue homogenates were tested by gel based PCR (G-PCR), quantitative-PCR (qPCR) and quantitative real time reverse transcriptase PCR (qRT-PCR) and viral culture. There were 87/114 (76.3%) swabs positive for at least one virus by at least one test. All necropsy cases were positive for at least one virus. Of 121 cases, positives included 18/121 (14.9%) BoHV-1; 19/121 (15.7%) BVDV; 76/121 (62.8%) BoCV; 11/121 (9.1%) BRSV; and 10/121 (8.3%) PI3V. For nasal swabs, G-PCR (5 viruses) detected 44/114 (38.6%); q-PCR and qRT-PCR (4 viruses) detected 81/114 (71.6%); and virus isolation detected 40/114 (35.1%). Most were positive for only one or two tests, but not all three tests. Necropsy cases had positives: 5/7 G-PCR, 5/7 q-PCR and qRT-PCR, and all were positive by cell culture. In some cases, G-PCR and both real time PCR were negative for BoHV-1, BVDV, and PI3V in samples positive by culture. PCR did not differentiate field from vaccines strains of BoHV-1, BVDV, and PI3V. However based on sequencing and analysis, field and vaccine strains of culture positive BoHV-1, BoCV, BVDV, and PI3V, 11/18 (61.1%) of BoHV-1 isolates, 6/17 (35.3%) BVDV isolates, and 1/10 (10.0%) PI3V identified as vaccine. BRSV was only identified by PCR testing. Interpretation of laboratory tests is appropriate as molecular based tests and virus isolation cannot separate field from vaccine strains. Additional testing using sequencing appears appropriate for identifying vaccine

  13. Estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in Australian live export cattle.

    Science.gov (United States)

    Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; O'Hara, Amanda J

    2015-01-01

    The prevalence of organisms known to be associated with bovine respiratory disease (BRD) was investigated in cattle prior to export. A quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: Bovine coronavirus (BoCV; Betacoronavirus 1), Bovine herpesvirus 1 (BoHV-1), Bovine viral diarrhea virus 1 (BVDV-1), Bovine respiratory syncytial virus (BRSV), Bovine parainfluenza virus 3 (BPIV-3), Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. Between 2010 and 2012, nasal swabs were collected from 1,484 apparently healthy cattle destined for export to the Middle East and Russian Federation. In addition, whole blood samples from 334 animals were tested for antibodies to BoHV-1, BRSV, BVDV-1, and BPIV-3 using enzyme-linked immunosorbent assay. The nasal prevalence of BoCV at the individual animal level was 40.1%. The nasal and seroprevalence of BoHV-1, BRSV, BVDV-1, and BPIV-3 was 1.0% and 39%, 1.2% and 46%, 3.0% and 56%, and 1.4% and 87%, respectively. The nasal prevalence of H. somni, M. bovis, M. haemolytica, and P. multocida was 42%, 4.8%, 13.4%, and 26%, respectively. Significant differences in nasal and seroprevalence were detected between groups of animals from different geographical locations. The results of the current study provide baseline data on the prevalence of organisms associated with BRD in Australian live export cattle in the preassembly period. This data could be used to develop strategies for BRD prevention and control prior to loading. © 2014 The Author(s).

  14. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    2011-08-01

    Full Text Available Respiratory syncytial virus (RSV infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.

  15. Inhibition of G1P3 expression found in the differential display study on respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Li Lei

    2008-10-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the leading viral pathogen associated with bronchiolitis and lower respiratory tract disease in infants and young children worldwide. The respiratory epithelium is the primary initiator of pulmonary inflammation in RSV infections, which cause significant perturbations of global gene expression controlling multiple cellular processes. In this study, differential display reverse transcription polymerase chain reaction amplification was performed to examine mRNA expression in a human alveolar cell line (SPC-A1 infected with RSV. Results Of the 2,500 interpretable bands on denaturing polyacrylamide gels, 40 (1.6% cDNA bands were differentially regulated by RSV, in which 28 (70% appeared to be upregulated and another 12 (30% appeared to be downregulated. Forty of the expressed sequence tags (EST were isolated, and 20 matched homologs in GenBank. RSV infection upregulated the mRNA expression of chemokines CC and CXC and interfered with type α/β interferon-inducible gene expression by upregulation of MG11 and downregulation of G1P3. Conclusion RSV replication could induce widespread changes in gene expression including both positive and negative regulation and play a different role in the down-regulation of IFN-α and up-regulation of IFN-γ inducible gene expression, which suggests that RSV interferes with the innate antiviral response of epithelial cells by multiple mechanisms.

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

    Science.gov (United States)

    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.

  17. Evaluation of protective efficacy of respiratory syncytial virus vaccine against A and B subgroup human isolates in Korea.

    Directory of Open Access Journals (Sweden)

    Ji-Eun Jang

    Full Text Available Human respiratory syncytial virus (HRSV is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. HRSV is divided into two subgroups, HRSV-A and HRSV-B, based on sequence variation within the G gene. Despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for HRSV. In this study, we have detected and identified the HRSV by RT-PCR from nasopharyngeal aspirates of Korean pediatric patients. Interestingly, all HRSV-B isolates exhibited unique deletion of 6 nucleotides and duplication of 60 nucleotides in the G gene. We successfully amplified two isolates ('KR/A/09-8' belonging to HRSV-A and 'KR/B/10-12' to HRSV-B on large-scale, and evaluated the cross-protective efficacy of our recombinant adenovirus-based HRSV vaccine candidate, rAd/3xG, by challenging the immunized mice with these isolates. The single intranasal immunization with rAd/3xG protected the mice completely from KR/A/09-8 infection and partially from KR/B/10-12 infection. Our study contributes to the understanding of the genetic characteristics and distribution of subgroups in the seasonal HRSV epidemics in Korea and, for the first time, to the evaluation of the cross-protective efficacy of RSV vaccine against HRSV-A and -B field-isolates.

  18. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Viktoria Stab

    Full Text Available The Respiratory Syncytial Virus (RSV and Influenza A Virus (IAV are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.

  19. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus.

    Science.gov (United States)

    Stab, Viktoria; Nitsche, Sandra; Niezold, Thomas; Storcksdieck Genannt Bonsmann, Michael; Wiechers, Andrea; Tippler, Bettina; Hannaman, Drew; Ehrhardt, Christina; Uberla, Klaus; Grunwald, Thomas; Tenbusch, Matthias

    2013-01-01

    The Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV) are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA) of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.

  20. Meeting report: WHO consultation on Respiratory Syncytial Virus (RSV) vaccine development, Geneva, 25-26 April 2016.

    Science.gov (United States)

    Giersing, Birgitte K; Karron, Ruth A; Vekemans, Johan; Kaslow, David C; Moorthy, Vasee S

    2017-03-14

    Respiratory syncytial virus (RSV) is a leading viral cause of respiratory morbidity and mortality in infants and young children worldwide. Low and middle income countries (LMICs) account for approximately 99% of the global mortality estimates in this population, with up to 200,000 RSV deaths per year. The vaccine product development pipeline is diverse with the most advanced clinical candidate currently in phase III efficacy testing in pregnant women. In addition, a long-acting RSV-neutralizing monoclonal antibody (mAb) to be administered at birth to prevent serious RSV-related respiratory disease is in late stage clinical development, as are additional conventional mAb for use in high-risk infants. Thus, there is a realistic possibility that an effective new intervention to prevent RSV disease will be available in the next 5-10year horizon. In anticipation of this outcome, the Strategic Advisory Group of Experts for Immunization (SAGE), WHO's vaccine policy recommendation body, reviewed the status of RSV vaccine and monoclonal antibody development in April 2016. Although substantial progress towards licensure has broadened the research agenda to consider intervention impact and cost effectiveness, significant gaps remain in the data that will be needed to inform and support a policy recommendation for implementation. These aspects were the focus of WHO's second consultation on RSV vaccines and single dosage extended half-life mAb for prophylaxis. Copyright © 2017.